\r\n\tThe applications are those related to intelligent monitoring activities such as the quality assessment of the environmental matrices through the use of innovative approaches, case studies, best practices with bottom-up approaches, machine learning techniques, systems development (for example algorithms, sensors, etc.) to predict alterations of environmental matrices. The goal is also to be able to protect natural resources by making their use increasingly sustainable.
\r\n
\r\n\tContributions related to the development of prototypes and software with an open-source component are very welcome.
\r\n
\r\n\tThis book is intended to provide the reader with a comprehensive overview of the current state of the art in the field of Ambient Intelligence. A format rich in figures, tables, diagrams, and graphical abstracts is strongly encouraged.
",isbn:"978-1-83969-069-3",printIsbn:"978-1-83969-068-6",pdfIsbn:"978-1-83969-070-9",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,hash:"3fbf8f0bcc5cdff72aaf0949d7cbc12e",bookSignature:"Dr. Carmine Massarelli",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/10391.jpg",keywords:"Embedded Systems, Technologies, Sensors, Remote Sensing, Smart Homes, Smart Cities, Integrated Monitoring Techniques, Agroecosystem, Smart Public Spaces, Computer Vision, Image Processing, Open-Source",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 12th 2020",dateEndSecondStepPublish:"November 9th 2020",dateEndThirdStepPublish:"January 8th 2021",dateEndFourthStepPublish:"March 29th 2021",dateEndFifthStepPublish:"May 28th 2021",remainingDaysToSecondStep:"2 months",secondStepPassed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"Environmental technologist expert in the development of Smart Technologies for water management and environmental monitoring, characterization, and monitoring of contaminated and degraded sites, integration of spatial data such as standard methodologies, interoperability, spectral data infrastructures.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"315689",title:"Dr.",name:"Carmine",middleName:null,surname:"Massarelli",slug:"carmine-massarelli",fullName:"Carmine Massarelli",profilePictureURL:"https://mts.intechopen.com/storage/users/315689/images/system/315689.jpg",biography:"Main activities:\n-development of Smart Technologies for water management and environmental monitoring;\n-characterization and monitoring of contaminated and degraded sites;\n-implementation of early warning systems and impact assessment systems also from multitemporal monitoring;\n-integration of spatial data: methodologies, standards, interoperability, spatial data infrastructures;\n-use of open source IT systems for the processing, analysis, and integration of remote sensing data with airborne and satellite sensors for thematic purposes such as characterization, control, and analysis of the territory in support of environmental policies relating to contaminated sites;\n-evaluation of the contamination of environmental matrices with specific tests and chemical analyses;\n-installation of airborne sensors and definition of flight parameters for Earth observation, CASI-1500 hyperspectral and TABI-320 thermal sensors;\n-acquisition of spectral signatures of objects through Fieldspec portable spectroradiometer and creation of databases in SQL language;\n-use of tools such as Ground Penetrating Radar for the advanced investigation of the subsoil with law enforcement agencies.",institutionString:"National Research Council",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"National Research Council",institutionURL:null,country:{name:"Italy"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"9",title:"Computer and Information Science",slug:"computer-and-information-science"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"297737",firstName:"Mateo",lastName:"Pulko",middleName:null,title:"Mr.",imageUrl:"https://mts.intechopen.com/storage/users/297737/images/8492_n.png",email:"mateo.p@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. 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\n\t\t\t
1. Introduction
Wnts compromise a large family of secreted glycoproteins that have shown to be part of the signaling molecules that regulate several aspects of development such as axis formation and midbrain development [1, 2]. In mammals at least 19 Wnt members have been found. The interaction of a Wnt protein with members of the Frizzled (Fz) family of seven-pass transmembrane cell-surface receptors triggers the activation of the Wnt signaling pathway [3-5]. In human and mice, 10 members of the Fz family have been identified. In addition, receptor-like tyrosine kinase (Ryk) and receptor tyrosine kinase-like orphan receptor (Ror2) have been identified as alternative Wnt receptors [6-8]. Different Wnt signaling cascades are activated downstream the Wnt receptors, identified as Wnt/β-catenin or canonical pathway, and β-catenin-independent or non-canonical pathways. The canonical pathway involves the transcription of Wnt target genes, while activation of non-canonical Wnt pathways may induce either an increase in intracellular calcium concentration or activation of the c-Jun-N-terminal kinase (JNK) cascade [3, 9, 10].
The Wnt pathway participates in the development of the central nervous system (CNS) and growing evidence indicate that Wnts also regulates the function of the adult nervous system [11, 12]. In fact, most of the key components including Wnts and Fz receptors are expressed in the adult brain [13, 14]. Wnt ligands have shown to regulate synaptic assembly as well synaptic plasticity and neurotransmission [15-20], and more recently it has also been involved in the adult neurogenesis [21-25].
Deregulation of the Wnt signaling has been associated to several pathologies, been cancer the most widely documented [26-28]. More recently, altered Wnt signaling have been related to mental disorders, mood disorders and neurodegenerative diseases [12, 29-32].
In the first part of this chapter we will address what is currently known about the signaling cascades of canonical and non-canonical pathways. Then, we will review recent findings from our and other labs on the specific effects of different Wnt ligands on the structure of pre- and postsynaptic regions and on glutamatergic neurotransmission in hippocampal neurons. The synaptic role of some Fz receptors will also be reviewed. Finally, the neuroprotective effect of the Wnt signaling activation will be discussed mainly focused on the protection against the toxicity of Aβ-peptide aggregates associated to the pathogenesis of Alzheimer’s disease.
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2. The Wnt signaling pathway: Canonical and non–canonical signaling cascades
The binding of Wnt ligands to Fz receptors can trigger the activation of different signaling cascades. In addition to Fz, other proteins have been described as alternative receptors or co-receptors, such as the low-density lipoprotein receptor-related protein 5 (LRP5), LRP6, Ror1, Ror2 and Ryk [3, 33-36], increasing the complexity of the Wnt signaling activation. It has been suggested that the binding of Wnts to specific receptors/co-receptors may selectively activate distinct signaling pathways.
The first Wnt signaling pathway identified was the canonical Wnt/β-catenin pathway (Figure 1). In the absence of Wnt stimulation, the levels of cytoplasmic β-catenin are low since it is ubiquitinated and constantly degraded in the proteasome [37]. β-catenin is phosphorylated by casein kinase 1α (CK1α) and glycogen synthase kinase-3β (GSK-3β) in a multiprotein complex composed also of the scaffold protein axin and adenomatous polyposis coli (APC) [38-42]. Phosphorylated β-catenin is recognized by β-TrCP, which is part of an E3 ubiquitin ligase complex, and is ubiquitinated and subsequently degraded [43]. Activation of the Wnt/β-catenin pathway initiated by the binding of a Wnt ligand to a Fz receptor and coreceptors LRP5/6 activates the protein Dishevelled (Dvl) usually by phosphorylation, and triggers the recruitment of axin to the phosphorylated tail of LRP, inhibiting the degradation pathway consequently inducing the cytoplasmic stabilization of β-catenin which enters the nucleus and regulates the transcription of Wnt target genes [28]. Recently, it was shown that when the destruction complex is associated with phosphorylated LRP, it may still capture and phosphorylates β-catenin, but ubiquitination is blocked (Figure 1, right panel) [44].
In the nucleus, β-catenin binds to members of the family of T-cell factor (Tcf) and lymphoid enhancer factor (Lef) [45-47]; this binding displaces Groucho, which is bound to Tcf/Lef and recruits histone deacetylases (HDAC) to repress the transcription of Wnt target genes [48-51]. Several Wnt target genes have been identified including c-Myc, cyclin D1, Axin2, Calcium/calmodulin-dependent protein kinase type IV (CamKIV) [52-55]. In addition, by using an in silico analysis based on multiple Classification and Regression Tree (CART), 89 new genes were predicted to be targets of the Wnt/β-catenin pathway [56].
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Figure 1.
\n\t\t\t\t\t\tCanonical Wnt/β-catenin signaling pathway. (Left panel) In the absence of a Wnt protein, GSK-3β phosphorylates β-catenin which targets it for ubiquitination by β-TrCP and degradation in the proteasome. (Right panel) Activation of the signaling pathway by the binding of a Wnt ligand to Fz receptor and coreceptors LRP5/6 triggers the association of the destruction complex with phosphorylated LRP. In this condition, the complex may still capture and phosphorylate β-catenin, however the ubiquitination is blocked and it is stabilized in the cytoplasm and enters the nucleus to regulate the transcription of Wnt target genes.
There are at least two β-catenin-independent pathways: the planar cell polarity (PCP) pathway and the Ca2+ pathway (Figure 2). The PCP pathway was originally identified in Drosophila where it regulates tissue polarity and cell migration [10, 57]. This signaling pathway requires Fz receptors and Dvl and activates small GTPases including Rho and Rac and the protein kinase JNK. This pathway is also known as the Wnt/JNK pathway. The activation of the Wnt/Ca2+ pathway triggers the increase in intracellular Ca2+ levels and activates the protein kinases CamKII and protein kinase C (PKC) [10, 58]. It has been suggested that Wnt-mediated Ca2+ release involves heterotrimeric G proteins since it is inhibited by pertussis toxin [59]. As mentioned 10 Fz receptors are known in mammals. Fz receptors are seven-transmembrane-spanning receptors that belong to the G protein-coupled receptor (GPCR) list as a separate class [60]. Fz receptors have an extracellular amino-terminal region that contains a cysteine-rich domain (CRD) consisting of 120 to 125 residues with 10 conserved cysteines that is relevant for the binding of Wnt proteins [61]. Growing evidence indicate the involvement of G protein in the Wnt/Fz signaling. The first evidence came from inhibition of non-canonical Wnt effects by pertussis toxin [62]. Later on, many reports have indicated that heterotrimeric G protein participates of canonical and non-canonical Wnt signaling in Drosophila, Xenopus and mammals [63-69].
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Figure 2.
\n\t\t\t\t\t\tβ-catenin-independent Wnt signaling pathways. In the Wnt/JNK pathway or PCP pathway, a Wnt ligand through a Fz receptors and Dvl activates small GTPases including Rho and Rac and JNK, which in turns modulate cytoskeletal organization. The activation of the Wnt/Ca2+ pathway triggers an increase in intracellular Ca2+ levels which activates CamKII and PKC.
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3. Roles of the Wnt signaling pathway at central synapses
The Wnt signaling pathway has different roles during development linked to neurite patterning and synaptogenesis. Different Wnt ligands have been linked to the presynaptic assembly. In 1997, Salinas and co-workers demonstrated in cerebellar neurons that Wnt-7a increases the levels of synapsin I, a protein associated to synaptic vesicles [70]. Moreover, Wnt-7a mutant mice show a delay in the accumulation of synapsin I [71]. In hippocampal neurons Wnt-7a as well as Wnt-3a and Wnt-7b increases the number of pre-synaptic puncta suggesting a role for these ligands in presynaptic assembly [18, 72, 73]. In addition, Wnt-7a was found to stimulate recycling and endocytosis of synaptic vesicles using FM dyes [74]. In hippocampal neurons, Wnt-7a was also able to increase the expression as well as the clustering of the α7- nicotinic acetylcholine receptor (α7-nAChR), indicating that the Wnt signaling regulates the clustering of presynaptic receptors [75]. Interestingly, all these ligands are able to modulate presynaptic differentiation by activation of the Wnt/β-catenin signaling pathway, suggesting that some of the components associated with this pathway may be involved in the presynaptic effect. On the other hand, the non-canonical ligand Wnt-5a decreases the number of presynaptic terminals [72], indicating that canonical and non-canonical signaling pathways may have promoting and inhibitory effects on presynaptic differentiation respectively. In accordance, electrophysiological recordings on adult rat hippocampal slices showed that Wnt-7a, but not Wnt-5a, increased neurotransmitter release in CA3-CA1 synapses by decreasing paired pulse facilitation and increasing the frequency of miniature excitatory postsynaptic currents (mEPSC) [73]. Also, Wnt-7a/Dvl1 double mutant mice exhibit decreased mEPSC frequency at the mossy fiber-granule cell synapse revealing a defect in neurotransmitter release [18].
The Wnt signaling also plays relevant roles in the postsynaptic structure. Wnt-5a, which activates non-canonical Wnt signaling cascades in hippocampal neurons [19, 76], modulates postsynaptic assembly by increasing the clustering of the postsynaptic density protein-95 (PSD-95) and increases spine morphogenesis in cultured hippocampal neurons [15, 19]. PSD-95 is a scaffold protein of the postsynaptic density (PSD), which is a multiprotein complex that interacts with key molecules involved in the regulation of glutamate receptor targeting and trafficking and regulatory proteins relevant for neurotransmission [77, 78]. In hippocampal neurons, Wnt-5a induces a fast increase in the number of clusters of PSD-95 without affecting total levels of PSD-95 protein or presynaptic protein clustering [19]. This postsynaptic effect is dependent on Wnt/JNK signaling pathway as demonstrated by using JNK inhibitors. In long-term experiments, we observed that Wnt-5a is also able to increase the total number of synapses [79]. When hippocampal neurons were incubated with the formylated hexapeptide Foxy-5, which is derived from the sequence of Wnt-5a and mimics the full Wnt-5a molecule action in neurons and other systems [19, 80], there was an increase in PSD-95 since 1 hour, but after 24 hours an increase in the synaptic vesicle protein 2 (SV2) clustering was also observed. In consequence, there was an increase in the total number of synaptic contacts [79].
Also, we determined that Wnt-5a induced a transient formation of dendrite protrusions that resulted in a net increase of mature dendrite spines. Videomicroscopy revealed that Wnt-5a induced de novo formation of dendritic spines and also increased the size of the preexisting ones [15]. Interestingly, treatment with the soluble CRD region of Fz2, acting as a Wnt scavenger, decreased spine density in cultured neurons, supporting the physiological relevance of this finding and supporting the implication of Wnt ligands in dendrite spine morphogenesis. Wnt-7a is also able to increase the density and maturity of dendritic spines through a CamKII-dependent mechanism [81]. Wnt-7a rapidly activates CaMKII in spines and inhibition of this kinase abolishes the effects of Wnt-7a on spine growth and excitatory synaptic strength. This finding implicates the Wnt/Ca2+ signaling cascade in synaptic effects of Wnt ligands. Interestingly, Wnt-5a and Wnt-7a induces an increase in intracellular Ca2+ concentration [15, 81], supporting the activation of this non-canonical Wnt pathway.
In addition to the structural effects of Wnt ligands at the excitatory synapse, different Wnts have shown modulatory effects on glutamatergic neurotransmission. Wnt-3a modulates the recycling of synaptic vesicles in hippocampal synapses [73, 82] and is able to induce an increase in the frequency of mEPSC [20]. In hippocampal slices, blockade of Wnt signaling impairs long-term potentiation (LTP), whereas activation of Wnt signaling facilitates LTP [17]. In the case of Wnt-5a, acute application of this ligand in hippocampal slices increases the amplitude of field excitatory postsynaptic potentials (fEPSP) and upregulates synaptic NMDA receptor currents facilitating induction of LTP [15, 16]. Interestingly, Wnt-5a produced a two-step increase in the amplitude of NMDAR responses [16]. The mechanisms involved in this two-step effect of Wnt-5a were investigated by the delivery of specific protein kinase inhibitors via the recording pipette. Specifically, the role of PKC and JNK was investigated, since these are two known downstream kinases of the non-canonical pathway. Inhibition of Ca22+-dependent PKC isoforms with Go6976 or the more general PKC inhibitor calphostin C eliminated the first step of potentiation of NMDAR currents and did not affect the second one. On the contrary, the slower developing increase in NMDAR currents was blocked by the JNK inhibitors TI-JIP153-163 and SP600125. This indicate that there are two mechanisms involved in in the potentiation of NMDAR by Wnt-5a. There is a fast PKC-dependent potentiation and a slower JNK-dependent potentiation that does not require previous activation of PKC [16].
Wnt-5a also regulates postsynaptically the hippocampal inhibitory synapses [76]. Wnt-5a induces surface expression and maintenance of GABAA receptor in the membrane of hippocampal neurons, increases the amplitude of GABA-currents due to a postsynaptic mechanisms, and induces the recycling of functional GABAA receptors through activation of CaMKII [76]. Therefore Wnt-5a is able to modulate both, excitatory and inhibitory synapses which must be relevant for neurotransmission.
The novel role for Wnt ligands in synaptic transmission provides a mechanism for Wnt signaling to acutely modulate synaptic plasticity and brain function in later stages of development and in the mature organism. Importantly, neuronal activity modulates the release and expression of Wnt ligands which may be relevant for the function of these ligands during neurotransmission. Activation of NMDA receptors increases the expression of Wnt-2 in hippocampal neurons which then stimulates dendritic arborization [83]. On the other hand, tetanic stimulation induce NMDA receptor-dependent synaptic Wnt3a release [17]. The role for endogenous Wnts was supported by incubation of hippocampal slices with secreted Wnt inhibitors, such as secreted Frizzled-related protein-2 (sFRP-2), which showed that endogenous Wnt ligands are modulators of glutamatergic neurotransmission being necessary to maintain basal NMDA receptor synaptic transmission [15, 16].
The in vivo relevance for the role of Wnt signaling in activity-mediated synaptic connectivity was revealed in mice exposed to an enriched environment (EE). These animals showed increased complexity and number of large mossy fiber terminals in the CA3 region [84]. EE increased Wnt7a/b levels in CA3 pyramidal neurons and inhibiting Wnt signaling through locally applied sFRP-1, suppressed the effects of EE on synapse numbers and further reduced synapse numbers in control mice.
These findings show that Wnt ligands are important regulators of the synaptic structure during development and in adult neurons, and that the Wnt pathway is one of the signaling cascades regulated by neuronal activity that is involved in the regulation of neurotransmission in adult nervous system.
In addition to the role of Wnts, Fz receptor have also been involved in synaptic structure and function. In the hippocampus, we have determined that different Fz receptors have very different patterns of expression during development, being some of them highly expressed in adulthood and others during early development [85]. In addition, the distribution of Fzs in hippocampal neurons is also very specific. Some receptors, are located in the synaptic region, while others are mainly located in the soma or in the growth cones of young neurons [85]. These findings suggest that these receptors could be important regulators for the specific activation of the Wnt signaling cascades during the development of hippocampal circuits. In fact, we determined an association of the distribution with specific functions. In hippocampal neurons, Fz1 is located in the synaptic region co-localizing with presynaptic proteins and with active synaptic vesicle recycling sites [82]. Interestingly, overexpression of Fz1 increased the number of clusters of Bassoon, a component of the active zone involved in the structural organization of neurotransmitter release sites that is recruited early during synapse formation [86], suggesting that Fz1 regulates synaptic differentiation. In agreement, treatment with the extracellular CRD of Fz1 decreased Bassoon clustering which was not observed with the CRD of Fz2, indicating a receptor specificity for the synaptic effect [82]. Fz5 also has a role in mature neurons where it modulates the synaptogenic effect of Wnt7a [87]. As well as Fz1, Fz5 is present in synaptosomes and colocalizes with synaptic markers, and changes in the expression of this receptor modulates the density of synaptic sites [87]. In addition to its function in mature neurons, Fz5 was shown to be in high levels in the growth cones of developing hippocampal neurons [85], and we have recently determined that this receptor is involved in neural polarization (unpublished results). We determined that overexpression of Fz5 triggers a mislocalization of axonal proteins such as Tau-1 and phosphorylated MAP1B (MAP1BP), which change their distribution to the whole cell suggesting altered polarization. When the expression of Fz5 is knocked-down by shRNA, MAP1BP is not polarized and is almost completely lost. These findings suggest that in developing hippocampal neurons Fz5 is relevant for neural polarization. These studies indicate that Fz receptors are relevant players in both the developing and the adult nervous system and support the notion that the Wnt signaling pathway is crucial for different aspects of the development and function of the CNS.
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4. Role of Wnt signaling in adult neurogenesis
In the adult brain, there are two regions where there is a continuous generation of new neurons (Figure 3A), the subventricular zone (SVZ) of the lateral ventricles [88] and the subgranular zone (SGZ) in the hippocampal dentate gyrus [89]. In the SVZ, astrocyte-like neural stem cells (NSCs), called type B1 cells, generate type C cells that rapidly proliferate and give rise to type A neuroblasts (Figure 3B). These cells migrate through the rostral migratory stream to the olfactory bulb where they became interneurons [88] (Figure 3A). In the SGZ, radial and non-radial neural precursor cells give rise to transient amplifying progenitors that generate neuroblasts and then became immature neurons that extend dendrites toward the molecular layer and project their axons through the hilus toward the CA3 region [90] (Figure 3C). Newborn neurons then mature and fully integrate into the preexisting hippocampal circuitry.
Adult neurogenesis is highly regulated by intrinsic and extrinsic mechanisms. Many signaling pathways have been identified as regulators of different aspects of neurogenesis. Notch, Shh, BMPs, and Wnts are part of the signaling molecules of the niche that regulate the maintenance, activation and fate specification of neural precursor cells [91, 92].
In Wnt/β-catenin reporter mice (BATGAL) it was shown that this pathway is active in the SGZ and the dentate granule cell layer [23]. In that study, authors determined that Wnt3 is expressed in adult hippocampal astrocytes and that adult hippocampal progenitor (AHP) cells express key components of the Wnt/β-catenin signaling pathway. These findings suggested that the Wnt pathway may be involved in the regulation of adult neurogenesis. In vitro analysis in cultured cells revealed that Wnts derived from hippocampal astrocytes stimulate Wnt/β-catenin signaling in isolated AHPs inducing their neuronal commitment [23]. The effect of the Wnt signaling was supported in vivo using lentiviral vectors expressing Wnt3a or a secreted mutant Wnt1 protein that blocks Wnt signaling. Lentiviruses were stereotactically injected into the dentate gyrus of rats. As assessed by the incorporation of the nucleotide analog BrdU and immunodetection of the immature neuron protein doublecortin (DCX), blocking the Wnt signaling decreases adult hippocampal neurogenesis while stimulating this pathway has the opposite effect [23]. More recently, and by using the same lentiviral approach to block Wnt signaling in the dentate gyrus of adult rats it was shown that Wnt-mediated adult hippocampal neurogenesis contributes to learning and memory [93]. In the SVZ, β-catenin signaling also plays a role in the proliferation of progenitor cells in the adult mouse brain [94]. Retrovirus-mediated expression of a stabilized β-catenin promoted the proliferation of type C cells and inhibited their differentiation into neuroblasts. Also in the SVZ, transduction of the β-catenin inhibitor axin by intracranial lentiviral delivery decreased cell proliferation as revealed by decreased BrdU labeling [95], further supporting a role for Wnt/β-catenin signaling in neural stem cell proliferation in the neurogenic areas of adult brain.
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Figure 3.
\n\t\t\t\t\t\tNeurogenesis in the adult brain. (A) Schematic representation of adult rodent brain highlighting the two neurogenic regions. The hippocampus and the SVZ (boxed). (B) Schematic of the SVZ in the wall of the lateral ventricles. Distinct stem/progenitor cell types (types B, C, and A) are shown. (C) Neurogenesis in the SGZ of the hippocampal dentate gyrus. The progression of radial type 1 cells to mature newborn granule neurons is schematized.
The Wnt-mediated effects in neurogenesis may be caused by the transcriptional activation of NeuroD1 which is dependent on the Wnt/β-catenin signaling activation [25]. NeuroD1 is a basic helix-loop-helix transcription factor important for the generation of granule cell and olfactory neuron in the embryonic and adult brain [96]. NeuroD1 gene promoter has overlapping DNA-binding site for Sox2 and TCF/LEF, then the activation of this gene implies activation of the canonical Wnt pathway and removal of Sox2 repression from the NeuroD1 gene promoter [25]. More recently, Prox1 was also determined as a target of the Wnt/β-catenin pathway relevant for neurogenesis [22]. Prox1 is expressed in newborn and mature granule cells and is required for the proper differentiation and survival of newborn granule cells, but not for the maintenance of granule cells after they have fully matured [22].
In addition, Wnts could indirectly modulate adult neurogenesis thorough their effects on neuronal activity. As previously described, different Wnts regulate glutamatergic neurotransmission, and evidence indicates that neural progenitor cells respond to neuronal activity as part of their differentiation program [97]. GABA is an important modulator of adult hippocampal neurogenesis being critical for the proper development and maturation of adult-born neurons [98-100]. Interestingly, Wnt-5a through activation of CaMKII, induces the recycling of functional GABAA receptors on hippocampal neurons and modulates inhibitory synapses [76].
As mentioned, in neurogenic niches Wnts are provided by astrocytes [23], and during aging it was reported that the levels of Wnt3 protein and the number of Wnt3-secreting astrocytes declines [101], which may be one of the factors underlying the impairment of neurogenesis that is observed in aging [102, 103]. On the contrary, running, that is a potent stimulator of adult neurogenesis in the SGZ [104] was found to significantly increase de novo expression of Wnt-3 [101], pointing to the Wnt pathway as one of the factors involved in running-mediated increase in neurogenesis. In addition to astrocytes-derived Wnts, an autocrine Wnt signaling activity has been observed in adult hippocampal progenitors (AHPs) derived from adult rat brains. Inhibiting this autocrine Wnt signaling increases the number of neurons formed and leads to a loss of multipotency among AHPs indicating that this autocrine pathway may preserve the balance between neural stem cell maintenance and differentiation [105].
The Wnt signaling has also been involved in the mechanism of the orphan nuclear receptor TLX (also known as NR2E1), which is an important regulator of neural stem cell maintenance and self-renewal in embryonic and adult brains [106, 107] and is involved in neurogenesis in the SVZ [108] and hippocampus [109]. To stimulate neural stem cell proliferation and self-renewal TLX activates the Wnt/β-catenin pathway in adult mouse neural stem cells by activating the expression of Wnt-7a, which expression was found to be downregulated in TLX-null mice, through binding to two TLX binding sites present in the Wnt-7a gene promoter [95]. Wnt-7a is important for adult neural stem cell proliferation in vivo since there is a decreased BrdU labeling in the SGZ and SVZ of adult Wnt7a knockout mice. In TLX-/- mice, intracranial lentiviral transduction of active β-catenin led to a considerable rescue of cell proliferation in the SVZ, suggesting that Wnt/β-catenin acts downstream of TLX to regulate neural stem cell proliferation in vivo [95].
It has been shown that low oxygen is associated with increased levels of β-catenin in vivo, and that hypoxia inducible factor-1α (HIF-1α) modulates the Wnt/β-catenin signaling in embryonic stem cells exposed to low oxygen [110]. Recently, we determined in vivo that hypoxia stimulates the activation of the Wnt/β-catenin signaling pathway in the hippocampus of adult mice (our unpublished results), and stimulates cell proliferation in the SGZ of 2 month old wild-type mice.
Altogether, these findings indicate that the Wnt pathway is relevant not only for the development of the nervous system but also for the development of new neurons in the adult brain, being important for the maintenance and self-renewal of the stem cell pool and for the commitment and proliferation of new neurons.
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5. Wnt signaling in Alzheimer’s disease
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by a progressive deterioration of cognitive abilities, cerebral accumulation of extracellular amyloid plaques composed mainly of amyloid-β peptide (Aβ), and synaptic alterations [111]. In addition to the accumulation of Aβ aggregates, which is a product of the processing of the amyloid precursor protein (APP), cytoskeletal alterations associated to the abnormal phosphorylation of the microtubule associated protein tau [112, 113] are early manifestations that lead to aberrant remodeling of dendrites and axons, the appearance of dystrophic neurites, synaptic loss [114], and eventually progressive loss of neuronal populations [112].
During more than a decade, a strong relationship between an impaired Wnt signaling pathway activity and neuronal damage in AD has been raised [31, 115-118]. Different studies have shown that Wnt signaling components are altered in AD [119-124], and in addition, the Wnt signaling pathway has been related to other neurodegenerative disorders such as autism and schizophrenia [30, 125]. Among the Wnt components that are affected in AD, it was shown that β-catenin levels are reduced in AD patients carrying presenilin-1 (PS-1)-inherited mutations [124], while the secreted Wnt antagonist Dickkopf-1 (Dkk1) is elevated in postmortem AD brains and brains from transgenic mouse models for AD [121, 126]. A variant of the LRP6 has been associated with late-onset AD, which confers low levels of Wnt signaling [119]. In addition, genetic studies show a link between Wnt signaling and AD. Epidemiological data show an increased risk for AD in populations where the allele 4 of apo-lipoprotein E (apoE4) is present. Interestingly apoE4 causes inhibition of the canonical Wnt signaling in PC12 cells upon stimulation with Wnt-7a as determined by luciferase activities and nuclear β-catenin levels [127]. Aβ directly binds to the extracellular CRD of Fz5 at or in close proximity to the Wnt-binding site inhibiting the canonical Wnt signaling pathway [128], linking directly Aβ to Wnt impairment. Moreover, the exposure of cultured rat hippocampal neurons to Aβ results in inhibition of canonical Wnt signaling as determined by destabilization of endogenous levels of β-catenin, increase in GSK-3β activity, and a decrease in the expression of some Wnt target genes [129]. Moreover, acute exposure to Aβ increases Dkk1 mRNA levels in hippocampal brain slices, which seems to be associated to synaptic loss induced by Aβ [130].
As mentioned, one of the hallmarks of AD brains is the abnormal phosphorylation of the tau protein which accumulates as intraneuronal neurofibrillary tangles [131]. Several kinases can phosphorylate tau in vitro; however, the bulk of the information supports that Cdk5, extracellular signal-related kinase 2, microtubule affinity-regulating kinase and GSK-3β, a key component of the Wnt cascade, are the most relevant kinases for tau phosphorylation in vivo [132, 133]. Cultured neurons exposed to Aβ show an increased GSK-3β activity [134, 135], and active GSK-3β has been found in brains staged for AD neurofibrillary changes, with a concomitant decrease in β-catenin levels and an increase in tau hyperphosphorylation [136]. Also, neurodegeneration and spatial learning deficits have been observed in GSK-3β conditional transgenic mice [137, 138]. Interestingly, a study shows that the phosphorylation of tau antagonizes apoptosis by stabilizing β-catenin; therefore, up-regulation of β-catenin during tau phosphorylation prevents the cell from going into apoptosis. Increasing levels of phosphorylated tau was correlated with increased levels of nuclear β-catenin, and the knockdown of β-catenin antagonizes the anti-apoptotic effects of tau [139]. These findings support a role of β-catenin as a survival element in AD.
Several studies have shown neuroprotective properties of the Wnt signaling activation against the toxicity of Aβ peptide. In cultured hippocampal neurons, exposure to Aβ aggregates causes a decrease in endogenous β-catenin levels, and this effect was overcome by direct activation of the pathway with Wnt-3a conditioned media [117, 129]. The protective effect of Wnt-3a against the toxicity of Aβ oligomers was shown to be mediated by Fz1 receptor, since this effect is modulated by the expression levels of Fz1 in both, PC12 cells and hippocampal neurons [14]. Overexpression of Fz1 significantly increased cell survival induced by Wnt-3a and diminished caspase-3 activation, while knocking-down the expression of the receptor by antisense oligonucleotides decreased the stabilization of β-catenin induced by Wnt-3a and decreased the neuroprotive effect elicited by this Wnt ligand [14].
In agreement with the effect of Wnt-3a, inhibition of GSK-3β by lithium protects hippocampal neurons from Aβ-induced damage. More importantly, in vivo lithium treatment of double transgenic APPswe/PSEN1ΔE9 mice, which is a well characterized in vivo model of AD that shows most hallmarks of the disease [140], reduced spatial memory impairment, decreased Aβ oligomers and the activation of astrocytes and microglia [141]. In vivo, lithium treatment activated the Wnt signaling as shown by the increase in β-catenin and by the inhibition of GSK-3β [141]. These studies suggest that the loss of normal Wnt/β-catenin signaling activity may be involved in the Aβ-dependent neurodegeneration observed in AD and that the activation of the pathway might have beneficial effects for the treatment of the disease [12].
APPswe/PSEN1ΔE9 mice show decreased levels of adult neurogenesis [142]. In these mice, we evaluated the effect of hypoxia on the generation of new neurons in the hippocampus. As previously mentioned hypoxia induces the activation of the Wnt/β-catenin signaling pathway in the hippocampus of wild-type mice. Mice were exposed to low oxygen and neurogenesis was evaluated by incorporation of BrdU and double staining with DCX. It was determined that hypoxia is a strong stimulator of neurogenesis in AD mice (our unpublished results). Currently we are evaluating whether this effect is related to the activation of the canonical Wnt pathway. Also, we have observed that voluntary wheel running strongly increased neurogenesis in APPswe/PSEN1ΔE9 mice and also decreased Aβ burden and tau phosphorylation (our unpublished results). As previously mentioned, voluntary running was found to increase de novo expression of Wnt-3 [101], suggesting that the effects observed in runner AD mice could involve the activation of the Wnt signaling pathway.
In addition to the role of the canonical Wnt signaling, we have studied whether Wnt-5a is able to protect neurons against Aβ oligomers synaptotoxicity [143]. Synaptic failure is an early event in AD, and soluble Aβ oligomers are proposed to be responsible for the synaptic pathology that occurs before the plaque deposition and neuronal death [74, 144]. Electrophysiological analysis of Schaffer collaterals-CA1 glutamatergic transmission in hippocampal slices demonstrated that Wnt-5a prevents the decrease in the amplitude of fEPSP and EPSCs induced by Aβ oligomers, indicating that Wnt-5a prevents the synaptic damage triggered by Aβ [143]. Moreover, Wnt-5a prevented the decrease in the postsynaptic density scaffold protein PSD-95 and synaptic loss in cultured hippocampal neurons [143], supporting that Wnt-5a improves synaptic function in the presence of Aβ.
Additionally, the activation of several signaling pathways that crosstalk with the Wnt pathway also supports the neuroprotective potential of the Wnt cascades in AD [12].
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6. Conclusions
As we have discussed throughout this Chapter, the Wnt signaling pathway has fundamental roles in the development and function of the CNS. As discussed, the canonical and non-canonical Wnt signaling cascades have shown to be important for the formation and structure of central synapses, and in addition to the structural effects, Wnt ligands acutely modulate synaptic transmission and plasticity. Also, in the adult brain the Wnt pathway is one of the signaling cascades that regulates the generation of new neurons in neurogenic niches. Importantly, different stimuli that regulate neurogenesis involve the regulation of the Wnt signaling, implicating this pathway as a relevant player in the modulation of this physiological process.
Considering all the discussed roles of Wnts, it was expected that alterations in the Wnt cascades leads to diseases associated to the nervous system. In fact, deregulation of the Wnt pathway has been related to mental disorders, mood disorders and neurodegenerative diseases. As we have discussed, a bulk of evidence associate Wnt dysfunction to AD, and strongly point to a neuroprotective potential of the Wnt cascades as a therapeutic approach. Future work should focus on explore the therapeutic benefits of stimulating the Wnt signaling pathway in vivo.
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Acknowledgments
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We thank to Felipe G. Serrano for his contribution in the artwork. This work was supported by Grants from FONDECYT (N°1120156) and the Basal Center of Excellence in Science and Technology (CONICYT-PFB12/2007) to NCI and FONDECYT (N°11110012) and Insertion of Postdoctoral Researchers in the Academy (CONICYT-79090027) to LV-N.
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\n',keywords:null,chapterPDFUrl:"https://cdn.intechopen.com/pdfs/43854.pdf",chapterXML:"https://mts.intechopen.com/source/xml/43854.xml",downloadPdfUrl:"/chapter/pdf-download/43854",previewPdfUrl:"/chapter/pdf-preview/43854",totalDownloads:2468,totalViews:472,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,dateSubmitted:"April 30th 2012",dateReviewed:null,datePrePublished:null,datePublished:"March 27th 2013",dateFinished:null,readingETA:"0",abstract:null,reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/43854",risUrl:"/chapter/ris/43854",book:{slug:"trends-in-cell-signaling-pathways-in-neuronal-fate-decision"},signatures:"Nibaldo C. Inestrosa and Lorena Varela-Nallar",authors:[{id:"157413",title:"Dr.",name:"Nibaldo C.",middleName:null,surname:"Inestrosa",fullName:"Nibaldo C. Inestrosa",slug:"nibaldo-c.-inestrosa",email:"ninestrosa@bio.puc.cl",position:null,institution:{name:"Pontifical Catholic University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"157428",title:"Dr.",name:"Lorena",middleName:null,surname:"Varela-Nallar",fullName:"Lorena Varela-Nallar",slug:"lorena-varela-nallar",email:"lpvarela@uc.cl",position:null,institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. The Wnt signaling pathway: Canonical and non–canonical signaling cascades",level:"1"},{id:"sec_3",title:"3. Roles of the Wnt signaling pathway at central synapses",level:"1"},{id:"sec_4",title:"4. Role of Wnt signaling in adult neurogenesis",level:"1"},{id:"sec_5",title:"5. Wnt signaling in Alzheimer’s disease",level:"1"},{id:"sec_6",title:"6. Conclusions",level:"1"},{id:"sec_7",title:"Acknowledgments",level:"1"}],chapterReferences:[{id:"B1",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNusse\n\t\t\t\t\t\t\tR\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVarmus\n\t\t\t\t\t\t\tH\n\t\t\t\t\t\t\n\t\t\t\t\tThree decades of Wnts: a personal perspective on how a scientific field developed. EMBO J 2012\n\t\t\t\t\t31\n\t\t\t\t\t12\n\t\t\t\t\t2670\n\t\t\t\t\t84\n\t\t\t\t\n\t\t\t'},{id:"B2",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVan Amerongen\n\t\t\t\t\t\t\tR\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNusse\n\t\t\t\t\t\t\tR\n\t\t\t\t\t\t\n\t\t\t\t\tTowards an integrated view of Wnt signaling in development. Development (Cambridge, England) 2009\n\t\t\t\t\t136\n\t\t\t\t\t19\n\t\t\t\t\t3205\n\t\t\t\t\t14\n\t\t\t\t\n\t\t\t'},{id:"B3",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGordon\n\t\t\t\t\t\t\tM. D\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNusse\n\t\t\t\t\t\t\tR\n\t\t\t\t\t\t\n\t\t\t\t\tWnt signaling: multiple pathways, multiple receptors, and multiple transcription factors. J Biol Chem 2006\n\t\t\t\t\t281\n\t\t\t\t\t32\n\t\t\t\t\t22429\n\t\t\t\t\t33\n\t\t\t\t\n\t\t\t'},{id:"B4",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSchulte\n\t\t\t\t\t\t\tG\n\t\t\t\t\t\t\n\t\t\t\t\tInternational Union of Basic and Clinical Pharmacology. LXXX. The class Frizzled receptors. Pharmacol Rev 2010\n\t\t\t\t\t62\n\t\t\t\t\t4\n\t\t\t\t\t632\n\t\t\t\t\t67\n\t\t\t\t\n\t\t\t'},{id:"B5",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWang\n\t\t\t\t\t\t\tH. Y\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLiu\n\t\t\t\t\t\t\tT\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMalbon\n\t\t\t\t\t\t\tC. C\n\t\t\t\t\t\t\n\t\t\t\t\tStructure-function analysis of Frizzleds. Cell Signal 2006\n\t\t\t\t\t18\n\t\t\t\t\t7\n\t\t\t\t\t934\n\t\t\t\t\t41\n\t\t\t\t\n\t\t\t'},{id:"B6",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKeeble\n\t\t\t\t\t\t\tT. R\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHalford\n\t\t\t\t\t\t\tM. M\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSeaman\n\t\t\t\t\t\t\tC\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKee\n\t\t\t\t\t\t\tN\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMacheda\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAnderson\n\t\t\t\t\t\t\tR. B\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tStacker\n\t\t\t\t\t\t\tS. A\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCooper\n\t\t\t\t\t\t\tH. M\n\t\t\t\t\t\t\n\t\t\t\t\tThe Wnt receptor Ryk is required for Wnt5a-mediated axon guidance on the contralateral side of the corpus callosum. J Neurosci 2006\n\t\t\t\t\t26\n\t\t\t\t\t21\n\t\t\t\t\t5840\n\t\t\t\t\t8\n\t\t\t\t\n\t\t\t'},{id:"B7",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOishi\n\t\t\t\t\t\t\tI\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSuzuki\n\t\t\t\t\t\t\tH\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOnishi\n\t\t\t\t\t\t\tN\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTakada\n\t\t\t\t\t\t\tR\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKani\n\t\t\t\t\t\t\tS\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOhkawara\n\t\t\t\t\t\t\tB\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKoshida\n\t\t\t\t\t\t\tI\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSuzuki\n\t\t\t\t\t\t\tK\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYamada\n\t\t\t\t\t\t\tG\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSchwabe\n\t\t\t\t\t\t\tG. C\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMundlos\n\t\t\t\t\t\t\tS\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tShibuya\n\t\t\t\t\t\t\tH\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTakada\n\t\t\t\t\t\t\tS\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMinami\n\t\t\t\t\t\t\tY\n\t\t\t\t\t\t\n\t\t\t\t\tThe receptor tyrosine kinase Ror2 is involved in non-canonical Wnt5a/JNK signalling pathway. Genes Cells 2003\n\t\t\t\t\t8\n\t\t\t\t\t7\n\t\t\t\t\t645\n\t\t\t\t\t54\n\t\t\t\t\n\t\t\t'},{id:"B8",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHo\n\t\t\t\t\t\t\tH. Y\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSusman\n\t\t\t\t\t\t\tM. W\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBikoff\n\t\t\t\t\t\t\tJ. B\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRyu\n\t\t\t\t\t\t\tY. K\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJonas\n\t\t\t\t\t\t\tA. M\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHu\n\t\t\t\t\t\t\tL\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKuruvilla\n\t\t\t\t\t\t\tR\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGreenberg\n\t\t\t\t\t\t\tM. E\n\t\t\t\t\t\t\n\t\t\t\t\tWnt5a-Ror-Dishevelled signaling constitutes a core developmental pathway that controls tissue morphogenesis. Proc Natl Acad Sci U S A 2012\n\t\t\t\t\t109\n\t\t\t\t\t11\n\t\t\t\t\t4044\n\t\t\t\t\t51\n\t\t\t\t\n\t\t\t'},{id:"B9",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAngers\n\t\t\t\t\t\t\tS\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMoon\n\t\t\t\t\t\t\tR. T\n\t\t\t\t\t\t\n\t\t\t\t\tProximal events in Wnt signal transduction. Nat Rev Mol Cell Biol 2009\n\t\t\t\t\t10\n\t\t\t\t\t7\n\t\t\t\t\t468\n\t\t\t\t\t77\n\t\t\t\t\n\t\t\t'},{id:"B10",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVeeman\n\t\t\t\t\t\t\tM. T\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAxelrod\n\t\t\t\t\t\t\tJ. D\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMoon\n\t\t\t\t\t\t\tR. T\n\t\t\t\t\t\t\n\t\t\t\t\tA second canon. Functions and mechanisms of beta-catenin-independent Wnt signaling. Developmental cell 2003\n\t\t\t\t\t5\n\t\t\t\t\t3\n\t\t\t\t\t367\n\t\t\t\t\t77\n\t\t\t\t\n\t\t\t'},{id:"B11",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSalinas\n\t\t\t\t\t\t\tP. C\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZou\n\t\t\t\t\t\t\tY\n\t\t\t\t\t\t\n\t\t\t\t\tWnt signaling in neural circuit assembly. Annu Rev Neurosci 2008\n\t\t\t\t\t31\n\t\t\t\t\t339\n\t\t\t\t\n\t\t\t'},{id:"B12",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tInestrosa\n\t\t\t\t\t\t\tN. C\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tArenas\n\t\t\t\t\t\t\tE\n\t\t\t\t\t\t\n\t\t\t\t\tEmerging roles of Wnts in the adult nervous system. Nature reviews 2010\n\t\t\t\t\t11\n\t\t\t\t\t2\n\t\t\t\t\t77\n\t\t\t\t\t86\n\t\t\t\t\n\t\t\t'},{id:"B13",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tShimogori\n\t\t\t\t\t\t\tT\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVansant\n\t\t\t\t\t\t\tJ\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPaik\n\t\t\t\t\t\t\tE\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGrove\n\t\t\t\t\t\t\tE. A\n\t\t\t\t\t\t\n\t\t\t\t\tMembers of the Wnt, Fz, and Frp gene families expressed in postnatal mouse cerebral cortex. J Comp Neurol 2004\n\t\t\t\t\t473\n\t\t\t\t\t4\n\t\t\t\t\t496\n\t\t\t\t\t510\n\t\t\t\t\n\t\t\t'},{id:"B14",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChacon\n\t\t\t\t\t\t\tM. A\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVarela-Nallar\n\t\t\t\t\t\t\tL\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tInestrosa\n\t\t\t\t\t\t\tN. C\n\t\t\t\t\t\t\n\t\t\t\t\tFrizzled-1 is involved in the neuroprotective effect of Wnt3a against Abeta oligomers. J Cell Physiol 2008\n\t\t\t\t\t217\n\t\t\t\t\t1\n\t\t\t\t\t215\n\t\t\t\t\t27\n\t\t\t\t\n\t\t\t'},{id:"B15",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVarela-Nallar\n\t\t\t\t\t\t\tL\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAlfaro\n\t\t\t\t\t\t\tI. E\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSerrano\n\t\t\t\t\t\t\tF. G\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tParodi\n\t\t\t\t\t\t\tJ\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tInestrosa\n\t\t\t\t\t\t\tN. C\n\t\t\t\t\t\t\n\t\t\t\t\tWingless-type family member 5A (Wnt-5a) stimulates synaptic differentiation and function of glutamatergic synapses. Proc Natl Acad Sci U S A 2010\n\t\t\t\t\t107\n\t\t\t\t\t49\n\t\t\t\t\t21164\n\t\t\t\t\t9\n\t\t\t\t\n\t\t\t'},{id:"B16",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCerpa\n\t\t\t\t\t\t\tW\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGambrill\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tInestrosa\n\t\t\t\t\t\t\tN. C\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBarria\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\tRegulation of NMDA-receptor synaptic transmission by Wnt signaling. J Neurosci 2011\n\t\t\t\t\t31\n\t\t\t\t\t26\n\t\t\t\t\t9466\n\t\t\t\t\t71\n\t\t\t\t\n\t\t\t'},{id:"B17",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChen\n\t\t\t\t\t\t\tJ\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPark\n\t\t\t\t\t\t\tC. S\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTang\n\t\t\t\t\t\t\tS. J\n\t\t\t\t\t\t\n\t\t\t\t\tActivity-dependent synaptic Wnt release regulates hippocampal long term potentiation. J Biol Chem 2006\n\t\t\t\t\t281\n\t\t\t\t\t17\n\t\t\t\t\t11910\n\t\t\t\t\t6\n\t\t\t\t\n\t\t\t'},{id:"B18",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAhmad-Annuar\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCiani\n\t\t\t\t\t\t\tL\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSimeonidis\n\t\t\t\t\t\t\tI\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHerreros\n\t\t\t\t\t\t\tJ\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFredj\n\t\t\t\t\t\t\tN. B\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRosso\n\t\t\t\t\t\t\tS. B\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHall\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBrickley\n\t\t\t\t\t\t\tS\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSalinas\n\t\t\t\t\t\t\tP. C\n\t\t\t\t\t\t\n\t\t\t\t\tSignaling across the synapse: a role for Wnt and Dishevelled in presynaptic assembly and neurotransmitter release. J Cell Biol 2006\n\t\t\t\t\t174\n\t\t\t\t\t1\n\t\t\t\t\t127\n\t\t\t\t\t39\n\t\t\t\t\n\t\t\t'},{id:"B19",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFarias\n\t\t\t\t\t\t\tG. G\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAlfaro\n\t\t\t\t\t\t\tI. E\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCerpa\n\t\t\t\t\t\t\tW\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGrabowski\n\t\t\t\t\t\t\tC. P\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGodoy\n\t\t\t\t\t\t\tJ. A\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBonansco\n\t\t\t\t\t\t\tC\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tInestrosa\n\t\t\t\t\t\t\tN. C\n\t\t\t\t\t\t\n\t\t\t\t\tWnt-5a/JNK signaling promotes the clustering of PSD-95 in hippocampal neurons. J Biol Chem 2009\n\t\t\t\t\t284\n\t\t\t\t\t23\n\t\t\t\t\t15857\n\t\t\t\t\t66\n\t\t\t\t\n\t\t\t'},{id:"B20",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAvila\n\t\t\t\t\t\t\tM. E\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSepulveda\n\t\t\t\t\t\t\tF. J\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBurgos\n\t\t\t\t\t\t\tC. F\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMoraga-Cid\n\t\t\t\t\t\t\tG\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tParodi\n\t\t\t\t\t\t\tJ\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMoon\n\t\t\t\t\t\t\tR. T\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAguayo\n\t\t\t\t\t\t\tL. G\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOpazo\n\t\t\t\t\t\t\tC\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDe Ferrari\n\t\t\t\t\t\t\tG. V\n\t\t\t\t\t\t\n\t\t\t\t\tCanonical Wnt3a modulates intracellular calcium and enhances excitatory neurotransmission in hippocampal neurons. J Biol Chem 2010\n\t\t\t\t\t285\n\t\t\t\t\t24\n\t\t\t\t\t18939\n\t\t\t\t\t47\n\t\t\t\t\n\t\t\t'},{id:"B21",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tClevers\n\t\t\t\t\t\t\tH\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNusse\n\t\t\t\t\t\t\tR\n\t\t\t\t\t\t\n\t\t\t\t\tWnt/beta-catenin signaling and disease. Cell 2012\n\t\t\t\t\t149\n\t\t\t\t\t6\n\t\t\t\t\t1192\n\t\t\t\t\t205\n\t\t\t\t\n\t\t\t'},{id:"B22",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKaralay\n\t\t\t\t\t\t\tO\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDoberauer\n\t\t\t\t\t\t\tK\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVadodaria\n\t\t\t\t\t\t\tK. C\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKnobloch\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBerti\n\t\t\t\t\t\t\tL\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMiquelajauregui\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSchwark\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJagasia\n\t\t\t\t\t\t\tR\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTaketo\n\t\t\t\t\t\t\tM. M\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTarabykin\n\t\t\t\t\t\t\tV\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLie\n\t\t\t\t\t\t\tD. C\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJessberger\n\t\t\t\t\t\t\tS\n\t\t\t\t\t\t\n\t\t\t\t\tProspero-related homeobox 1 gene (Prox1) is regulated by canonical Wnt signaling and has a stage-specific role in adult hippocampal neurogenesis. Proc Natl Acad Sci U S A (2011). , 108(14), 5807-12.\n\t\t\t'},{id:"B23",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLie\n\t\t\t\t\t\t\tD. C\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tColamarino\n\t\t\t\t\t\t\tS. A\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSong\n\t\t\t\t\t\t\tH. J\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDesire\n\t\t\t\t\t\t\tL\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMira\n\t\t\t\t\t\t\tH\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tConsiglio\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLein\n\t\t\t\t\t\t\tE. S\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJessberger\n\t\t\t\t\t\t\tS\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLansford\n\t\t\t\t\t\t\tH\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDearie\n\t\t\t\t\t\t\tA. R\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGage\n\t\t\t\t\t\t\tF. H\n\t\t\t\t\t\t\n\t\t\t\t\tWnt signalling regulates adult hippocampal neurogenesis. Nature 2005\n\t\t\t\t\t437\n\t\t\t\t\t7063\n\t\t\t\t\t1370\n\t\t\t\t\t5\n\t\t\t\t\n\t\t\t'},{id:"B24",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZhang\n\t\t\t\t\t\t\tL\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYang\n\t\t\t\t\t\t\tX\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYang\n\t\t\t\t\t\t\tS\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZhang\n\t\t\t\t\t\t\tJ\n\t\t\t\t\t\t\n\t\t\t\t\tThe Wnt /beta-catenin signaling pathway in the adult neurogenesis. Eur J Neurosci 2011\n\t\t\t\t\t33\n\t\t\t\t\t1\n\t\t\t\t\t1\n\t\t\t\t\t8\n\t\t\t\t\n\t\t\t'},{id:"B25",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKuwabara\n\t\t\t\t\t\t\tT\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHsieh\n\t\t\t\t\t\t\tJ\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMuotri\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYeo\n\t\t\t\t\t\t\tG\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWarashina\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLie\n\t\t\t\t\t\t\tD. C\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMoore\n\t\t\t\t\t\t\tL\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNakashima\n\t\t\t\t\t\t\tK\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAsashima\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGage\n\t\t\t\t\t\t\tF. H\n\t\t\t\t\t\t\n\t\t\t\t\tWnt-mediated activation of NeuroD1 and retro-elements during adult neurogenesis. Nat Neurosci 2009\n\t\t\t\t\t12\n\t\t\t\t\t9\n\t\t\t\t\t1097\n\t\t\t\t\t105\n\t\t\t\t\n\t\t\t'},{id:"B26",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPolakis\n\t\t\t\t\t\t\tP\n\t\t\t\t\t\t\n\t\t\t\t\tThe many ways of Wnt in cancer. Curr Opin Genet Dev 2007\n\t\t\t\t\t17\n\t\t\t\t\t1\n\t\t\t\t\t45\n\t\t\t\t\t51\n\t\t\t\t\n\t\t\t'},{id:"B27",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKlaus\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBirchmeier\n\t\t\t\t\t\t\tW\n\t\t\t\t\t\t\n\t\t\t\t\tWnt signalling and its impact on development and cancer. Nat Rev Cancer 2008\n\t\t\t\t\t8\n\t\t\t\t\t5\n\t\t\t\t\t387\n\t\t\t\t\t98\n\t\t\t\t\n\t\t\t'},{id:"B28",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLogan\n\t\t\t\t\t\t\tC. Y\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNusse\n\t\t\t\t\t\t\tR\n\t\t\t\t\t\t\n\t\t\t\t\tThe Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol (2004). , 20, 781-810.\n\t\t\t'},{id:"B29",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDe Ferrari\n\t\t\t\t\t\t\tG. V\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMoon\n\t\t\t\t\t\t\tR. T\n\t\t\t\t\t\t\n\t\t\t\t\tThe ups and downs of Wnt signaling in prevalent neurological disorders. Oncogene 2006\n\t\t\t\t\t25\n\t\t\t\t\t57\n\t\t\t\t\t7545\n\t\t\t\t\t53\n\t\t\t\t\n\t\t\t'},{id:"B30",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLovestone\n\t\t\t\t\t\t\tS\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKillick\n\t\t\t\t\t\t\tR\n\t\t\t\t\t\t\n\t\t\t\t\tDi Forti M,Murray R. Schizophrenia as a GSK-3 dysregulation disorder. Trends Neurosci 2007\n\t\t\t\t\t30\n\t\t\t\t\t4\n\t\t\t\t\t142\n\t\t\t\t\t9\n\t\t\t\t\n\t\t\t'},{id:"B31",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDe Ferrari\n\t\t\t\t\t\t\tG. V\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tInestrosa\n\t\t\t\t\t\t\tN. C\n\t\t\t\t\t\t\n\t\t\t\t\tWnt signaling function in Alzheimer’s disease. Brain Res Brain Res Rev 2000\n\t\t\t\t\t33\n\t\t\t\t\t1\n\t\t\t\t\t1\n\t\t\t\t\t12\n\t\t\t\t\n\t\t\t'},{id:"B32",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWilliams\n\t\t\t\t\t\t\tR. S\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHarwood\n\t\t\t\t\t\t\tA. J\n\t\t\t\t\t\t\n\t\t\t\t\tLithium therapy and signal transduction. Trends Pharmacol Sci 2000\n\t\t\t\t\t21\n\t\t\t\t\t2\n\t\t\t\t\t61\n\t\t\t\t\t4\n\t\t\t\t\n\t\t\t'},{id:"B33",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFradkin\n\t\t\t\t\t\t\tL. G\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDura\n\t\t\t\t\t\t\tJ. M\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNoordermeer\n\t\t\t\t\t\t\tJ. N\n\t\t\t\t\t\t\n\t\t\t\t\tRyks: new partners for Wnts in the developing and regenerating nervous system. Trends Neurosci 2009\n\t\t\t\t\t33\n\t\t\t\t\t2\n\t\t\t\t\t84\n\t\t\t\t\t92\n\t\t\t\t\n\t\t\t'},{id:"B34",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGreen\n\t\t\t\t\t\t\tJ. L\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKuntz\n\t\t\t\t\t\t\tS. G\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSternberg\n\t\t\t\t\t\t\tP. W\n\t\t\t\t\t\t\n\t\t\t\t\tRor receptor tyrosine kinases: orphans no more. Trends Cell Biol 2008\n\t\t\t\t\t18\n\t\t\t\t\t11\n\t\t\t\t\t536\n\t\t\t\t\t44\n\t\t\t\t\n\t\t\t'},{id:"B35",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKikuchi\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYamamoto\n\t\t\t\t\t\t\tH\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKishida\n\t\t\t\t\t\t\tS\n\t\t\t\t\t\t\n\t\t\t\t\tMultiplicity of the interactions of Wnt proteins and their receptors. Cell Signal 2007\n\t\t\t\t\t19\n\t\t\t\t\t4\n\t\t\t\t\t659\n\t\t\t\t\t71\n\t\t\t\t\n\t\t\t'},{id:"B36",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCadigan\n\t\t\t\t\t\t\tK. M\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLiu\n\t\t\t\t\t\t\tY. I\n\t\t\t\t\t\t\n\t\t\t\t\tWnt signaling: complexity at the surface. J Cell Sci 2006Pt 3) 395-402.\n\t\t\t'},{id:"B37",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAberle\n\t\t\t\t\t\t\tH\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBauer\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tStappert\n\t\t\t\t\t\t\tJ\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKispert\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKemler\n\t\t\t\t\t\t\tR\n\t\t\t\t\t\t\n\t\t\t\t\tbeta-catenin is a target for the ubiquitin-proteasome pathway. EMBO J 1997\n\t\t\t\t\t16\n\t\t\t\t\t13\n\t\t\t\t\t3797\n\t\t\t\t\t804\n\t\t\t\t\n\t\t\t'},{id:"B38",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tIkeda\n\t\t\t\t\t\t\tS\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKishida\n\t\t\t\t\t\t\tS\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYamamoto\n\t\t\t\t\t\t\tH\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMurai\n\t\t\t\t\t\t\tH\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKoyama\n\t\t\t\t\t\t\tS\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKikuchi\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\tAxin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3beta and beta-catenin and promotes GSK-3beta-dependent phosphorylation of beta-catenin. EMBO J 1998\n\t\t\t\t\t17\n\t\t\t\t\t5\n\t\t\t\t\t1371\n\t\t\t\t\t84\n\t\t\t\t\n\t\t\t'},{id:"B39",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKishida\n\t\t\t\t\t\t\tS\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYamamoto\n\t\t\t\t\t\t\tH\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tIkeda\n\t\t\t\t\t\t\tS\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKishida\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSakamoto\n\t\t\t\t\t\t\tI\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKoyama\n\t\t\t\t\t\t\tS\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKikuchi\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\tAxin, a negative regulator of the wnt signaling pathway, directly interacts with adenomatous polyposis coli and regulates the stabilization of beta-catenin. J Biol Chem 1998\n\t\t\t\t\t273\n\t\t\t\t\t18\n\t\t\t\t\t10823\n\t\t\t\t\t6\n\t\t\t\t\n\t\t\t'},{id:"B40",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHart\n\t\t\t\t\t\t\tM. J\n\t\t\t\t\t\t\n\t\t\t\t\tde los Santos R, Albert IN, Rubinfeld B,Polakis P. Downregulation of beta-catenin by human Axin and its association with the APC tumor suppressor, beta-catenin and GSK3 beta. Curr Biol 1998\n\t\t\t\t\t8\n\t\t\t\t\t10\n\t\t\t\t\t573\n\t\t\t\t\t81\n\t\t\t\t\n\t\t\t'},{id:"B41",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tItoh\n\t\t\t\t\t\t\tK\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKrupnik\n\t\t\t\t\t\t\tV. E\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSokol\n\t\t\t\t\t\t\tS. Y\n\t\t\t\t\t\t\n\t\t\t\t\tAxis determination in Xenopus involves biochemical interactions of axin, glycogen synthase kinase 3 and beta-catenin. Curr Biol 1998\n\t\t\t\t\t8\n\t\t\t\t\t10\n\t\t\t\t\t591\n\t\t\t\t\t4\n\t\t\t\t\n\t\t\t'},{id:"B42",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSakanaka\n\t\t\t\t\t\t\tC\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWeiss\n\t\t\t\t\t\t\tJ. B\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWilliams\n\t\t\t\t\t\t\tL. T\n\t\t\t\t\t\t\n\t\t\t\t\tBridging of beta-catenin and glycogen synthase kinase-3beta by axin and inhibition of beta-catenin-mediated transcription. Proc Natl Acad Sci U S A 1998\n\t\t\t\t\t95\n\t\t\t\t\t6\n\t\t\t\t\t3020\n\t\t\t\t\t3\n\t\t\t\t\n\t\t\t'},{id:"B43",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLiu\n\t\t\t\t\t\t\tC\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLi\n\t\t\t\t\t\t\tY\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSemenov\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHan\n\t\t\t\t\t\t\tC\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBaeg\n\t\t\t\t\t\t\tG. H\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTan\n\t\t\t\t\t\t\tY\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZhang\n\t\t\t\t\t\t\tZ\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLin\n\t\t\t\t\t\t\tX\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHe\n\t\t\t\t\t\t\tX\n\t\t\t\t\t\t\n\t\t\t\t\tControl of beta-catenin phosphorylation/degradation by a dual-kinase mechanism. Cell 2002\n\t\t\t\t\t108\n\t\t\t\t\t6\n\t\t\t\t\t837\n\t\t\t\t\t47\n\t\t\t\t\n\t\t\t'},{id:"B44",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLi\n\t\t\t\t\t\t\tV. S\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNg\n\t\t\t\t\t\t\tS. S\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBoersema\n\t\t\t\t\t\t\tP. J\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLow\n\t\t\t\t\t\t\tT. Y\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKarthaus\n\t\t\t\t\t\t\tW. R\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGerlach\n\t\t\t\t\t\t\tJ. P\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMohammed\n\t\t\t\t\t\t\tS\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHeck\n\t\t\t\t\t\t\tA. J\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMaurice\n\t\t\t\t\t\t\tM. M\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMahmoudi\n\t\t\t\t\t\t\tT\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tClevers\n\t\t\t\t\t\t\tH\n\t\t\t\t\t\t\n\t\t\t\t\tWnt signaling through inhibition of beta-catenin degradation in an intact Axin1 complex. Cell 2012\n\t\t\t\t\t149\n\t\t\t\t\t6\n\t\t\t\t\t1245\n\t\t\t\t\t56\n\t\t\t\t\n\t\t\t'},{id:"B45",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBehrens\n\t\t\t\t\t\t\tJ\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVon Kries\n\t\t\t\t\t\t\tJ. P\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKuhl\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBruhn\n\t\t\t\t\t\t\tL\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWedlich\n\t\t\t\t\t\t\tD\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGrosschedl\n\t\t\t\t\t\t\tR\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBirchmeier\n\t\t\t\t\t\t\tW\n\t\t\t\t\t\t\n\t\t\t\t\tFunctional interaction of beta-catenin with the transcription factor LEF-1. Nature 1996\n\t\t\t\t\t382\n\t\t\t\t\t6592\n\t\t\t\t\t638\n\t\t\t\t\t42\n\t\t\t\t\n\t\t\t'},{id:"B46",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tEastman\n\t\t\t\t\t\t\tQ\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGrosschedl\n\t\t\t\t\t\t\tR\n\t\t\t\t\t\t\n\t\t\t\t\tRegulation of LEF-1/TCF transcription factors by Wnt and other signals. Curr Opin Cell Biol 1999\n\t\t\t\t\t11\n\t\t\t\t\t2\n\t\t\t\t\t233\n\t\t\t\t\t40\n\t\t\t\t\n\t\t\t'},{id:"B47",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHuber\n\t\t\t\t\t\t\tO\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKorn\n\t\t\t\t\t\t\tR\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMclaughlin\n\t\t\t\t\t\t\tJ\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOhsugi\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHerrmann\n\t\t\t\t\t\t\tB. G\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKemler\n\t\t\t\t\t\t\tR\n\t\t\t\t\t\t\n\t\t\t\t\tNuclear localization of beta-catenin by interaction with transcription factor LEF-1. Mech Dev 1996\n\t\t\t\t\t59\n\t\t\t\t\t1\n\t\t\t\t\t3\n\t\t\t\t\t10\n\t\t\t\t\n\t\t\t'},{id:"B48",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRoose\n\t\t\t\t\t\t\tJ\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMolenaar\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPeterson\n\t\t\t\t\t\t\tJ\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHurenkamp\n\t\t\t\t\t\t\tJ\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBrantjes\n\t\t\t\t\t\t\tH\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMoerer\n\t\t\t\t\t\t\tP\n\t\t\t\t\t\t\n\t\t\t\t\tvan de Wetering M, Destree O,Clevers H. The Xenopus Wnt effector XTcf-3 interacts with Groucho-related transcriptional repressors. Nature 1998\n\t\t\t\t\t395\n\t\t\t\t\t6702\n\t\t\t\t\t608\n\t\t\t\t\t12\n\t\t\t\t\n\t\t\t'},{id:"B49",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCavallo\n\t\t\t\t\t\t\tR. A\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCox\n\t\t\t\t\t\t\tR. T\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMoline\n\t\t\t\t\t\t\tM. M\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRoose\n\t\t\t\t\t\t\tJ\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPolevoy\n\t\t\t\t\t\t\tG. A\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tClevers\n\t\t\t\t\t\t\tH\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPeifer\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBejsovec\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\tDrosophila Tcf and Groucho interact to repress Wingless signalling activity. Nature 1998\n\t\t\t\t\t395\n\t\t\t\t\t6702\n\t\t\t\t\t604\n\t\t\t\t\t8\n\t\t\t\t\n\t\t\t'},{id:"B50",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHurlstone\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\tClevers H. T-cell factors: turn-ons and turn-offs. EMBO J 2002\n\t\t\t\t\t21\n\t\t\t\t\t10\n\t\t\t\t\t2303\n\t\t\t\t\t11\n\t\t\t\t\n\t\t\t'},{id:"B51",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChen\n\t\t\t\t\t\t\tG\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFernandez\n\t\t\t\t\t\t\tJ\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMische\n\t\t\t\t\t\t\tS\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCourey\n\t\t\t\t\t\t\tA. J\n\t\t\t\t\t\t\n\t\t\t\t\tA functional interaction between the histone deacetylase Rpd3 and the corepressor groucho in Drosophila development. Genes Dev 1999\n\t\t\t\t\t13\n\t\t\t\t\t17\n\t\t\t\t\t2218\n\t\t\t\t\t30\n\t\t\t\t\n\t\t\t'},{id:"B52",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tArrazola\n\t\t\t\t\t\t\tM. S\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVarela-Nallar\n\t\t\t\t\t\t\tL\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tColombres\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tToledo\n\t\t\t\t\t\t\tE. M\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCruzat\n\t\t\t\t\t\t\tF\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPavez\n\t\t\t\t\t\t\tL\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAssar\n\t\t\t\t\t\t\tR\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAravena\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGonzalez\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMontecino\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMaass\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMartinez\n\t\t\t\t\t\t\tS\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tInestrosa\n\t\t\t\t\t\t\tN. C\n\t\t\t\t\t\t\n\t\t\t\t\tCalcium/calmodulin-dependent protein kinase type IV is a target gene of the Wnt/beta-catenin signaling pathway. J Cell Physiol 2009\n\t\t\t\t\t221\n\t\t\t\t\t3\n\t\t\t\t\t658\n\t\t\t\t\t67\n\t\t\t\t\n\t\t\t'},{id:"B53",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJho\n\t\t\t\t\t\t\tE. H\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZhang\n\t\t\t\t\t\t\tT\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDomon\n\t\t\t\t\t\t\tC\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJoo\n\t\t\t\t\t\t\tC. K\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFreund\n\t\t\t\t\t\t\tJ. N\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCostantini\n\t\t\t\t\t\t\tF\n\t\t\t\t\t\t\n\t\t\t\t\tWnt/beta-catenin/Tcf signaling induces the transcription of Axin2, a negative regulator of the signaling pathway. Mol Cell Biol 2002\n\t\t\t\t\t22\n\t\t\t\t\t4\n\t\t\t\t\t1172\n\t\t\t\t\t83\n\t\t\t\t\n\t\t\t'},{id:"B54",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJung\n\t\t\t\t\t\t\tH. C\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKim\n\t\t\t\t\t\t\tK\n\t\t\t\t\t\t\n\t\t\t\t\tIdentification of MYCBP as a beta-catenin/LEF-1 target using DNA microarray analysis. Life Sci 2005\n\t\t\t\t\t77\n\t\t\t\t\t11\n\t\t\t\t\t1249\n\t\t\t\t\t62\n\t\t\t\t\n\t\t\t'},{id:"B55",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTetsu\n\t\t\t\t\t\t\tO\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMccormick\n\t\t\t\t\t\t\tF\n\t\t\t\t\t\t\n\t\t\t\t\tBeta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature 1999\n\t\t\t\t\t398\n\t\t\t\t\t6726\n\t\t\t\t\t422\n\t\t\t\t\t6\n\t\t\t\t\n\t\t\t'},{id:"B56",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHodar\n\t\t\t\t\t\t\tC\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAssar\n\t\t\t\t\t\t\tR\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tColombres\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAravena\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPavez\n\t\t\t\t\t\t\tL\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGonzalez\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMartinez\n\t\t\t\t\t\t\tS\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tInestrosa\n\t\t\t\t\t\t\tN. C\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMaass\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\tGenome-wide identification of new Wnt/beta-catenin target genes in the human genome using CART method. BMC Genomics (2010). ,11:348\n\t\t\t'},{id:"B57",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAdler\n\t\t\t\t\t\t\tP. N\n\t\t\t\t\t\t\n\t\t\t\t\tPlanar signaling and morphogenesis in Drosophila. Developmental cell 2002\n\t\t\t\t\t2\n\t\t\t\t\t5\n\t\t\t\t\t525\n\t\t\t\t\t35\n\t\t\t\t\n\t\t\t'},{id:"B58",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKohn\n\t\t\t\t\t\t\tA. D\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMoon\n\t\t\t\t\t\t\tR. T\n\t\t\t\t\t\t\n\t\t\t\t\tWnt and calcium signaling: beta-catenin-independent pathways. Cell Calcium (2005). , 38(3-4), 439-46\n\t\t\t'},{id:"B59",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSlusarski\n\t\t\t\t\t\t\tD. C\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYang-snyder\n\t\t\t\t\t\t\tJ\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBusa\n\t\t\t\t\t\t\tW. B\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMoon\n\t\t\t\t\t\t\tR. T\n\t\t\t\t\t\t\n\t\t\t\t\tModulation of embryonic intracellular Ca2+ signaling by Wnt-5A. Dev Biol 1997\n\t\t\t\t\t182\n\t\t\t\t\t1\n\t\t\t\t\t114\n\t\t\t\t\t20\n\t\t\t\t\n\t\t\t'},{id:"B60",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFoord\n\t\t\t\t\t\t\tS. M\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBonner\n\t\t\t\t\t\t\tT. I\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNeubig\n\t\t\t\t\t\t\tR. R\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRosser\n\t\t\t\t\t\t\tE. M\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPin\n\t\t\t\t\t\t\tJ. P\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDavenport\n\t\t\t\t\t\t\tA. P\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSpedding\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHarmar\n\t\t\t\t\t\t\tA. J\n\t\t\t\t\t\t\n\t\t\t\t\tInternational Union of Pharmacology. XLVI. G protein-coupled receptor list. Pharmacol Rev 2005\n\t\t\t\t\t57\n\t\t\t\t\t2\n\t\t\t\t\t279\n\t\t\t\t\t88\n\t\t\t\t\n\t\t\t'},{id:"B61",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDann\n\t\t\t\t\t\t\tC. E\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHsieh\n\t\t\t\t\t\t\tJ. C\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRattner\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSharma\n\t\t\t\t\t\t\tD\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNathans\n\t\t\t\t\t\t\tJ\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLeahy\n\t\t\t\t\t\t\tD. J\n\t\t\t\t\t\t\n\t\t\t\t\tInsights into Wnt binding and signalling from the structures of two Frizzled cysteine-rich domains. Nature 2001\n\t\t\t\t\t412\n\t\t\t\t\t6842\n\t\t\t\t\t86\n\t\t\t\t\t90\n\t\t\t\t\n\t\t\t'},{id:"B62",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSlusarski\n\t\t\t\t\t\t\tD. C\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCorces\n\t\t\t\t\t\t\tV. G\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMoon\n\t\t\t\t\t\t\tR. T\n\t\t\t\t\t\t\n\t\t\t\t\tInteraction of Wnt and a Frizzled homologue triggers G-protein-linked phosphatidylinositol signalling. Nature 1997\n\t\t\t\t\t390\n\t\t\t\t\t6658\n\t\t\t\t\t410\n\t\t\t\t\t3\n\t\t\t\t\n\t\t\t'},{id:"B63",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLiu\n\t\t\t\t\t\t\tX\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRubin\n\t\t\t\t\t\t\tJ. S\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKimmel\n\t\t\t\t\t\t\tA. R\n\t\t\t\t\t\t\n\t\t\t\t\tRapid, Wnt-induced changes in GSK3beta associations that regulate beta-catenin stabilization are mediated by Galpha proteins. Curr Biol 2005\n\t\t\t\t\t15\n\t\t\t\t\t22\n\t\t\t\t\t1989\n\t\t\t\t\t97\n\t\t\t\t\n\t\t\t'},{id:"B64",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSalmanian\n\t\t\t\t\t\t\tS\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNajafi\n\t\t\t\t\t\t\tS. M\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRafipour\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tArjomand\n\t\t\t\t\t\t\tM. R\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tShahheydari\n\t\t\t\t\t\t\tH\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAnsari\n\t\t\t\t\t\t\tS\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKashkooli\n\t\t\t\t\t\t\tL\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRasouli\n\t\t\t\t\t\t\tS. J\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJazi\n\t\t\t\t\t\t\tM. S\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMinaei\n\t\t\t\t\t\t\tT\n\t\t\t\t\t\t\n\t\t\t\t\tRegulation of GSK-3beta and beta-Catenin by Galphaq in HEK293T cells. Biochem Biophys Res Commun 2010\n\t\t\t\t\t395\n\t\t\t\t\t4\n\t\t\t\t\t577\n\t\t\t\t\t82\n\t\t\t\t\n\t\t\t'},{id:"B65",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNajafi\n\t\t\t\t\t\t\tS. M\n\t\t\t\t\t\t\n\t\t\t\t\tActivators of G proteins inhibit GSK-3beta and stabilize beta-Catenin in Xenopus oocytes. Biochem Biophys Res Commun 2009\n\t\t\t\t\t382\n\t\t\t\t\t2\n\t\t\t\t\t365\n\t\t\t\t\t9\n\t\t\t\t\n\t\t\t'},{id:"B66",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKatanaev\n\t\t\t\t\t\t\tV. L\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPonzielli\n\t\t\t\t\t\t\tR\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSemeriva\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTomlinson\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\tTrimeric G protein-dependent frizzled signaling in Drosophila. Cell 2005\n\t\t\t\t\t120\n\t\t\t\t\t1\n\t\t\t\t\t111\n\t\t\t\t\t22\n\t\t\t\t\n\t\t\t'},{id:"B67",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKatanaev\n\t\t\t\t\t\t\tV. L\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTomlinson\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\tDual roles for the trimeric G protein Go in asymmetric cell division in Drosophila. Proc Natl Acad Sci U S A 2006\n\t\t\t\t\t103\n\t\t\t\t\t17\n\t\t\t\t\t6524\n\t\t\t\t\t9\n\t\t\t\t\n\t\t\t'},{id:"B68",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJernigan\n\t\t\t\t\t\t\tK. K\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCselenyi\n\t\t\t\t\t\t\tC. S\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tThorne\n\t\t\t\t\t\t\tC. A\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHanson\n\t\t\t\t\t\t\tA. J\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTahinci\n\t\t\t\t\t\t\tE\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHajicek\n\t\t\t\t\t\t\tN\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOldham\n\t\t\t\t\t\t\tW. M\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLee\n\t\t\t\t\t\t\tL. A\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHamm\n\t\t\t\t\t\t\tH. E\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHepler\n\t\t\t\t\t\t\tJ. R\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKozasa\n\t\t\t\t\t\t\tT\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLinder\n\t\t\t\t\t\t\tM. E\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLee\n\t\t\t\t\t\t\tE\n\t\t\t\t\t\t\n\t\t\t\t\tGbetagamma activates GSK3 to promote LRP6-mediated beta-catenin transcriptional activity. Sci Signal 2010ra37.\n\t\t\t'},{id:"B69",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLiu\n\t\t\t\t\t\t\tX\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLiu\n\t\t\t\t\t\t\tT\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSlusarski\n\t\t\t\t\t\t\tD. C\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYang-snyder\n\t\t\t\t\t\t\tJ\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMalbon\n\t\t\t\t\t\t\tC. C\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMoon\n\t\t\t\t\t\t\tR. T\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWang\n\t\t\t\t\t\t\tH\n\t\t\t\t\t\t\n\t\t\t\t\tActivation of a frizzled-2/beta-adrenergic receptor chimera promotes Wnt signaling and differentiation of mouse F9 teratocarcinoma cells via Galphao and Galphat. Proc Natl Acad Sci U S A 1999\n\t\t\t\t\t96\n\t\t\t\t\t25\n\t\t\t\t\t14383\n\t\t\t\t\t8\n\t\t\t\t\n\t\t\t'},{id:"B70",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLucas\n\t\t\t\t\t\t\tF. R\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSalinas\n\t\t\t\t\t\t\tP. C\n\t\t\t\t\t\t\n\t\t\t\t\tWNT-7a induces axonal remodeling and increases synapsin I levels in cerebellar neurons. Dev Biol 1997\n\t\t\t\t\t192\n\t\t\t\t\t1\n\t\t\t\t\t31\n\t\t\t\t\t44\n\t\t\t\t\n\t\t\t'},{id:"B71",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHall\n\t\t\t\t\t\t\tA. C\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLucas\n\t\t\t\t\t\t\tF. R\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSalinas\n\t\t\t\t\t\t\tP. C\n\t\t\t\t\t\t\n\t\t\t\t\tAxonal remodeling and synaptic differentiation in the cerebellum is regulated by WNT-7a signaling. Cell 2000\n\t\t\t\t\t100\n\t\t\t\t\t5\n\t\t\t\t\t525\n\t\t\t\t\t35\n\t\t\t\t\n\t\t\t'},{id:"B72",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDavis\n\t\t\t\t\t\t\tE. K\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZou\n\t\t\t\t\t\t\tY\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGhosh\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\tWnts acting through canonical and noncanonical signaling pathways exert opposite effects on hippocampal synapse formation. Neural Dev (2008). , 3, 32.\n\t\t\t'},{id:"B73",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCerpa\n\t\t\t\t\t\t\tW\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGodoy\n\t\t\t\t\t\t\tJ. A\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAlfaro\n\t\t\t\t\t\t\tI\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFarias\n\t\t\t\t\t\t\tG. G\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMetcalfe\n\t\t\t\t\t\t\tM. J\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFuentealba\n\t\t\t\t\t\t\tR\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBonansco\n\t\t\t\t\t\t\tC\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tInestrosa\n\t\t\t\t\t\t\tN. C\n\t\t\t\t\t\t\n\t\t\t\t\tWnt-7a modulates the synaptic vesicle cycle and synaptic transmission in hippocampal neurons. J Biol Chem 2008\n\t\t\t\t\t283\n\t\t\t\t\t9\n\t\t\t\t\t5918\n\t\t\t\t\t27\n\t\t\t\t\n\t\t\t'},{id:"B74",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCerpa\n\t\t\t\t\t\t\tW\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDinamarca\n\t\t\t\t\t\t\tM. C\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tInestrosa\n\t\t\t\t\t\t\tN. C\n\t\t\t\t\t\t\n\t\t\t\t\tStructure-function implications in Alzheimer’s disease: effect of Abeta oligomers at central synapses. Curr Alzheimer Res 2008\n\t\t\t\t\t5\n\t\t\t\t\t3\n\t\t\t\t\t233\n\t\t\t\t\t43\n\t\t\t\t\n\t\t\t'},{id:"B75",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFarias\n\t\t\t\t\t\t\tG. G\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tValles\n\t\t\t\t\t\t\tA. S\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tColombres\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGodoy\n\t\t\t\t\t\t\tJ. A\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tToledo\n\t\t\t\t\t\t\tE. M\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLukas\n\t\t\t\t\t\t\tR. J\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBarrantes\n\t\t\t\t\t\t\tF. J\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tInestrosa\n\t\t\t\t\t\t\tN. C\n\t\t\t\t\t\t\n\t\t\t\t\tWnt-7a induces presynaptic colocalization of alpha 7-nicotinic acetylcholine receptors and adenomatous polyposis coli in hippocampal neurons. J Neurosci 2007\n\t\t\t\t\t27\n\t\t\t\t\t20\n\t\t\t\t\t5313\n\t\t\t\t\t25\n\t\t\t\t\n\t\t\t'},{id:"B76",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCuitino\n\t\t\t\t\t\t\tL\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGodoy\n\t\t\t\t\t\t\tJ. A\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFarias\n\t\t\t\t\t\t\tG. G\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCouve\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBonansco\n\t\t\t\t\t\t\tC\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFuenzalida\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tInestrosa\n\t\t\t\t\t\t\tN. C\n\t\t\t\t\t\t\n\t\t\t\t\tWnt-5a modulates recycling of functional GABAA receptors on hippocampal neurons. J Neurosci 2010\n\t\t\t\t\t30\n\t\t\t\t\t25\n\t\t\t\t\t8411\n\t\t\t\t\t20\n\t\t\t\t\n\t\t\t'},{id:"B77",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHan\n\t\t\t\t\t\t\tK\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKim\n\t\t\t\t\t\t\tE\n\t\t\t\t\t\t\n\t\t\t\t\tSynaptic adhesion molecules and PSD-95. Progress in neurobiology 2008\n\t\t\t\t\t84\n\t\t\t\t\t3\n\t\t\t\t\t263\n\t\t\t\t\t83\n\t\t\t\t\n\t\t\t'},{id:"B78",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLi\n\t\t\t\t\t\t\tZ\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSheng\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\tSome assembly required: the development of neuronal synapses. Nat Rev Mol Cell Biol 2003\n\t\t\t\t\t4\n\t\t\t\t\t11\n\t\t\t\t\t833\n\t\t\t\t\t41\n\t\t\t\t\n\t\t\t'},{id:"B79",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVarela-Nallar\n\t\t\t\t\t\t\tL\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tParodi\n\t\t\t\t\t\t\tJ\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFarias\n\t\t\t\t\t\t\tG. G\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tInestrosa\n\t\t\t\t\t\t\tN. C\n\t\t\t\t\t\t\n\t\t\t\t\tWnt-5a is a synaptogenic factor with neuroprotective properties against Abeta toxicity. Neurodegener Dis (2012). , 10(1-4), 23-6.\n\t\t\t'},{id:"B80",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSafholm\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLeandersson\n\t\t\t\t\t\t\tK\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDejmek\n\t\t\t\t\t\t\tJ\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNielsen\n\t\t\t\t\t\t\tC. K\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVilloutreix\n\t\t\t\t\t\t\tB. O\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAndersson\n\t\t\t\t\t\t\tT\n\t\t\t\t\t\t\n\t\t\t\t\tA formylated hexapeptide ligand mimics the ability of Wnt-5a to impair migration of human breast epithelial cells. J Biol Chem 2006\n\t\t\t\t\t281\n\t\t\t\t\t5\n\t\t\t\t\t2740\n\t\t\t\t\t9\n\t\t\t\t\n\t\t\t'},{id:"B81",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCiani\n\t\t\t\t\t\t\tL\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBoyle\n\t\t\t\t\t\t\tK. A\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDickins\n\t\t\t\t\t\t\tE\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSahores\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAnane\n\t\t\t\t\t\t\tD\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLopes\n\t\t\t\t\t\t\tD. M\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGibb\n\t\t\t\t\t\t\tA. J\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSalinas\n\t\t\t\t\t\t\tP. C\n\t\t\t\t\t\t\n\t\t\t\t\tWnt7a signaling promotes dendritic spine growth and synaptic strength through Ca2+/Calmodulin-dependent protein kinase II. Proc Natl Acad Sci U S A (2011). , 108(26), 10732-7.\n\t\t\t'},{id:"B82",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVarela-Nallar\n\t\t\t\t\t\t\tL\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGrabowski\n\t\t\t\t\t\t\tC. P\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAlfaro\n\t\t\t\t\t\t\tI. E\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAlvarez\n\t\t\t\t\t\t\tA. R\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tInestrosa\n\t\t\t\t\t\t\tN. C\n\t\t\t\t\t\t\n\t\t\t\t\tRole of the Wnt receptor Frizzled-1 in presynaptic differentiation and function. Neural Dev (2009). , 4, 41.\n\t\t\t'},{id:"B83",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWayman\n\t\t\t\t\t\t\tG. A\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tImpey\n\t\t\t\t\t\t\tS\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMarks\n\t\t\t\t\t\t\tD\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSaneyoshi\n\t\t\t\t\t\t\tT\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGrant\n\t\t\t\t\t\t\tW. F\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDerkach\n\t\t\t\t\t\t\tV\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSoderling\n\t\t\t\t\t\t\tT. R\n\t\t\t\t\t\t\n\t\t\t\t\tActivity-dependent dendritic arborization mediated by CaM-kinase I activation and enhanced CREB-dependent transcription of Wnt-2. Neuron 2006\n\t\t\t\t\t50\n\t\t\t\t\t6\n\t\t\t\t\t897\n\t\t\t\t\t909\n\t\t\t\t\n\t\t\t'},{id:"B84",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGogolla\n\t\t\t\t\t\t\tN\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGalimberti\n\t\t\t\t\t\t\tI\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDeguchi\n\t\t\t\t\t\t\tY\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCaroni\n\t\t\t\t\t\t\tP\n\t\t\t\t\t\t\n\t\t\t\t\tWnt signaling mediates experience-related regulation of synapse numbers and mossy fiber connectivities in the adult hippocampus. Neuron 2009\n\t\t\t\t\t62\n\t\t\t\t\t4\n\t\t\t\t\t510\n\t\t\t\t\t25\n\t\t\t\t\n\t\t\t'},{id:"B85",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVarela-Nallar\n\t\t\t\t\t\t\tL\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRamirez\n\t\t\t\t\t\t\tV. T\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGonzalez-billault\n\t\t\t\t\t\t\tC\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tInestrosa\n\t\t\t\t\t\t\tN. C\n\t\t\t\t\t\t\n\t\t\t\t\tFrizzled receptors in neurons: From growth cones to the synapse. Cytoskeleton (Hoboken) 2012\n\t\t\t\t\t69\n\t\t\t\t\t7\n\t\t\t\t\t528\n\t\t\t\t\t34\n\t\t\t\t\n\t\t\t'},{id:"B86",body:'\n\t\t\t\tZhai, R, Olias, G, Chung, W. J, Lester R. A, tom Dieck, S, Langnaese, K, Kreutz, M. R, Kindler, S, Gundelfinger, E. D, & Garner C. C. Temporal appearance of the presynaptic cytomatrix protein bassoon during synaptogenesis. Mol Cell Neurosci 2000\n\t\t\t\t\t15\n\t\t\t\t\t5\n\t\t\t\t\t417\n\t\t\t\t\t28\n\t\t\t\t\n\t\t\t'},{id:"B87",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSahores\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGibb\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSalinas\n\t\t\t\t\t\t\tP. C\n\t\t\t\t\t\t\n\t\t\t\t\tFrizzled-5, a receptor for the synaptic organizer Wnt7a, regulates activity-mediated synaptogenesis. Development (Cambridge, England) 2010\n\t\t\t\t\t137\n\t\t\t\t\t13\n\t\t\t\t\t2215\n\t\t\t\t\t25\n\t\t\t\t\n\t\t\t'},{id:"B88",body:'\n\t\t\t\tAlvarez-Buylla, A, & Garcia-Verdugo, J. M. Neurogenesis in adult subventricular zone. J Neurosci 2002\n\t\t\t\t\t22\n\t\t\t\t\t3\n\t\t\t\t\t629\n\t\t\t\t\t34\n\t\t\t\t\n\t\t\t'},{id:"B89",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGage\n\t\t\t\t\t\t\tF. H\n\t\t\t\t\t\t\n\t\t\t\t\tMammalian neural stem cells. Science (New York, N.Y.) (2000). 287\n\t\t\t\t\t5457\n\t\t\t\t\t1433\n\t\t\t\t\t8\n\t\t\t\t\n\t\t\t'},{id:"B90",body:'\n\t\t\t\tZhao, C, Teng, E. M, Summers, R. G Jr, Ming, G. L, & Gage, F. H. Distinct morphological stages of dentate granule neuron maturation in the adult mouse hippocampus. J Neurosci 2006\n\t\t\t\t\t26\n\t\t\t\t\t1\n\t\t\t\t\t3\n\t\t\t\t\t11\n\t\t\t\t\n\t\t\t'},{id:"B91",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSuh\n\t\t\t\t\t\t\tH\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDeng\n\t\t\t\t\t\t\tW\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGage\n\t\t\t\t\t\t\tF. H\n\t\t\t\t\t\t\n\t\t\t\t\tSignaling in adult neurogenesis. Annu Rev Cell Dev Biol (2009). , 25, 253-75.\n\t\t\t'},{id:"B92",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMing\n\t\t\t\t\t\t\tG. L\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSong\n\t\t\t\t\t\t\tH\n\t\t\t\t\t\t\n\t\t\t\t\tAdult neurogenesis in the mammalian brain: significant answers and significant questions. Neuron 2011\n\t\t\t\t\t70\n\t\t\t\t\t4\n\t\t\t\t\t687\n\t\t\t\t\t702\n\t\t\t\t\n\t\t\t'},{id:"B93",body:'\n\t\t\t\tJessberger, S, Clark, R. E, Broadbent, N. J, Clemenson, G. D Jr, Consiglio, A, Lie, D. C, Squire, L. R, & Gage, F. H. Dentate gyrus-specific knockdown of adult neurogenesis impairs spatial and object recognition memory in adult rats. Learn Mem 2009\n\t\t\t\t\t16\n\t\t\t\t\t2\n\t\t\t\t\t147\n\t\t\t\t\t54\n\t\t\t\t\n\t\t\t'},{id:"B94",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAdachi\n\t\t\t\t\t\t\tK\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMirzadeh\n\t\t\t\t\t\t\tZ\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSakaguchi\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYamashita\n\t\t\t\t\t\t\tT\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNikolcheva\n\t\t\t\t\t\t\tT\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGotoh\n\t\t\t\t\t\t\tY\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPeltz\n\t\t\t\t\t\t\tG\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGong\n\t\t\t\t\t\t\tL\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKawase\n\t\t\t\t\t\t\tT\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAlvarez-Buylla\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOkano\n\t\t\t\t\t\t\tH\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSawamoto\n\t\t\t\t\t\t\tK\n\t\t\t\t\t\t\n\t\t\t\t\tBeta-catenin signaling promotes proliferation of progenitor cells in the adult mouse subventricular zone. Stem Cells 2007\n\t\t\t\t\t25\n\t\t\t\t\t11\n\t\t\t\t\t2827\n\t\t\t\t\t36\n\t\t\t\t\n\t\t\t'},{id:"B95",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tQu\n\t\t\t\t\t\t\tQ\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSun\n\t\t\t\t\t\t\tG\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLi\n\t\t\t\t\t\t\tW\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYang\n\t\t\t\t\t\t\tS\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYe\n\t\t\t\t\t\t\tP\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZhao\n\t\t\t\t\t\t\tC\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYu\n\t\t\t\t\t\t\tR. T\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGage\n\t\t\t\t\t\t\tF. H\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tEvans\n\t\t\t\t\t\t\tR. M\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tShi\n\t\t\t\t\t\t\tY\n\t\t\t\t\t\t\n\t\t\t\t\tOrphan nuclear receptor TLX activates Wnt/beta-catenin signalling to stimulate neural stem cell proliferation and self-renewal. Nat Cell Biol 2010sup 1\n\t\t\t\t\t9\n\t\t\t\t\n\t\t\t'},{id:"B96",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGao\n\t\t\t\t\t\t\tZ\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tUre\n\t\t\t\t\t\t\tK\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAbles\n\t\t\t\t\t\t\tJ. L\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLagace\n\t\t\t\t\t\t\tD. C\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNave\n\t\t\t\t\t\t\tK. A\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGoebbels\n\t\t\t\t\t\t\tS\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tEisch\n\t\t\t\t\t\t\tA. J\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHsieh\n\t\t\t\t\t\t\tJ\n\t\t\t\t\t\t\n\t\t\t\t\tNeurod1 is essential for the survival and maturation of adult-born neurons. Nat Neurosci 2009\n\t\t\t\t\t12\n\t\t\t\t\t9\n\t\t\t\t\t1090\n\t\t\t\t\t2\n\t\t\t\t\n\t\t\t'},{id:"B97",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDeisseroth\n\t\t\t\t\t\t\tK\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSingla\n\t\t\t\t\t\t\tS\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tToda\n\t\t\t\t\t\t\tH\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMonje\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPalmer\n\t\t\t\t\t\t\tT. D\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMalenka\n\t\t\t\t\t\t\tR. C\n\t\t\t\t\t\t\n\t\t\t\t\tExcitation-neurogenesis coupling in adult neural stem/progenitor cells. Neuron 2004\n\t\t\t\t\t42\n\t\t\t\t\t4\n\t\t\t\t\t535\n\t\t\t\t\t52\n\t\t\t\t\n\t\t\t'},{id:"B98",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGe\n\t\t\t\t\t\t\tS\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGoh\n\t\t\t\t\t\t\tE. L\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSailor\n\t\t\t\t\t\t\tK. A\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKitabatake\n\t\t\t\t\t\t\tY\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMing\n\t\t\t\t\t\t\tG. L\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSong\n\t\t\t\t\t\t\tH\n\t\t\t\t\t\t\n\t\t\t\t\tGABA regulates synaptic integration of newly generated neurons in the adult brain. Nature 2006\n\t\t\t\t\t439\n\t\t\t\t\t7076\n\t\t\t\t\t589\n\t\t\t\t\t93\n\t\t\t\t\n\t\t\t'},{id:"B99",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJagasia\n\t\t\t\t\t\t\tR\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSteib\n\t\t\t\t\t\t\tK\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tEnglberger\n\t\t\t\t\t\t\tE\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHerold\n\t\t\t\t\t\t\tS\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFaus-kessler\n\t\t\t\t\t\t\tT\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSaxe\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGage\n\t\t\t\t\t\t\tF. H\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSong\n\t\t\t\t\t\t\tH\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLie\n\t\t\t\t\t\t\tD. C\n\t\t\t\t\t\t\n\t\t\t\t\tGABA-cAMP response element-binding protein signaling regulates maturation and survival of newly generated neurons in the adult hippocampus. J Neurosci 2009\n\t\t\t\t\t29\n\t\t\t\t\t25\n\t\t\t\t\t7966\n\t\t\t\t\t77\n\t\t\t\t\n\t\t\t'},{id:"B100",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTozuka\n\t\t\t\t\t\t\tY\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFukuda\n\t\t\t\t\t\t\tS\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNamba\n\t\t\t\t\t\t\tT\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSeki\n\t\t\t\t\t\t\tT\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHisatsune\n\t\t\t\t\t\t\tT\n\t\t\t\t\t\t\n\t\t\t\t\tGABAergic excitation promotes neuronal differentiation in adult hippocampal progenitor cells. Neuron 2005\n\t\t\t\t\t47\n\t\t\t\t\t6\n\t\t\t\t\t803\n\t\t\t\t\t15\n\t\t\t\t\n\t\t\t'},{id:"B101",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOkamoto\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tInoue\n\t\t\t\t\t\t\tK\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tIwamura\n\t\t\t\t\t\t\tH\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTerashima\n\t\t\t\t\t\t\tK\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSoya\n\t\t\t\t\t\t\tH\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAsashima\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKuwabara\n\t\t\t\t\t\t\tT\n\t\t\t\t\t\t\n\t\t\t\t\tReduction in paracrine Wnt3 factors during aging causes impaired adult neurogenesis. Faseb J 2011\n\t\t\t\t\t25\n\t\t\t\t\t10\n\t\t\t\t\t3570\n\t\t\t\t\t82\n\t\t\t\t\n\t\t\t'},{id:"B102",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKuhn\n\t\t\t\t\t\t\tH. G\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDickinson-anson\n\t\t\t\t\t\t\tH\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGage\n\t\t\t\t\t\t\tF. H\n\t\t\t\t\t\t\n\t\t\t\t\tNeurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J Neurosci 1996\n\t\t\t\t\t16\n\t\t\t\t\t6\n\t\t\t\t\t2027\n\t\t\t\t\t33\n\t\t\t\t\n\t\t\t'},{id:"B103",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVarela-Nallar\n\t\t\t\t\t\t\tL\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAranguiz\n\t\t\t\t\t\t\tF. C\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAbbott\n\t\t\t\t\t\t\tA. C\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSlater\n\t\t\t\t\t\t\tP. G\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tInestrosa\n\t\t\t\t\t\t\tN. C\n\t\t\t\t\t\t\n\t\t\t\t\tAdult hippocampal neurogenesis in aging and Alzheimer’s disease. Birth Defects Res C Embryo Today 2010\n\t\t\t\t\t90\n\t\t\t\t\t4\n\t\t\t\t\t284\n\t\t\t\t\t96\n\t\t\t\t\n\t\t\t'},{id:"B104",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVan Praag\n\t\t\t\t\t\t\tH\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKempermann\n\t\t\t\t\t\t\tG\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGage\n\t\t\t\t\t\t\tF. H\n\t\t\t\t\t\t\n\t\t\t\t\tRunning increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci 1999\n\t\t\t\t\t2\n\t\t\t\t\t3\n\t\t\t\t\t266\n\t\t\t\t\t70\n\t\t\t\t\n\t\t\t'},{id:"B105",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWexler\n\t\t\t\t\t\t\tE. M\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPaucer\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKornblum\n\t\t\t\t\t\t\tH. I\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPalmer\n\t\t\t\t\t\t\tT. D\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGeschwind\n\t\t\t\t\t\t\tD. H\n\t\t\t\t\t\t\n\t\t\t\t\tEndogenous Wnt signaling maintains neural progenitor cell potency. Stem Cells 2009\n\t\t\t\t\t27\n\t\t\t\t\t5\n\t\t\t\t\t1130\n\t\t\t\t\t41\n\t\t\t\t\n\t\t\t'},{id:"B106",body:'\n\t\t\t\tShi, Y. Chichung Lie, D, Taupin, P, Nakashima, K, Ray, J, Yu, R. T, Gage, F. H, & Evans, R. M. Expression and function of orphan nuclear receptor TLX in adult neural stem cells. Nature 2004\n\t\t\t\t\t427\n\t\t\t\t\t6969\n\t\t\t\t\t78\n\t\t\t\t\t83\n\t\t\t\t\n\t\t\t'},{id:"B107",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLi\n\t\t\t\t\t\t\tW\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSun\n\t\t\t\t\t\t\tG\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYang\n\t\t\t\t\t\t\tS\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tQu\n\t\t\t\t\t\t\tQ\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNakashima\n\t\t\t\t\t\t\tK\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tShi\n\t\t\t\t\t\t\tY\n\t\t\t\t\t\t\n\t\t\t\t\tNuclear receptor TLX regulates cell cycle progression in neural stem cells of the developing brain. Mol Endocrinol 2008\n\t\t\t\t\t22\n\t\t\t\t\t1\n\t\t\t\t\t56\n\t\t\t\t\t64\n\t\t\t\t\n\t\t\t'},{id:"B108",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLiu\n\t\t\t\t\t\t\tH. K\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBelz\n\t\t\t\t\t\t\tT\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBock\n\t\t\t\t\t\t\tD\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTakacs\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWu\n\t\t\t\t\t\t\tH\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLichter\n\t\t\t\t\t\t\tP\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChai\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSchutz\n\t\t\t\t\t\t\tG\n\t\t\t\t\t\t\n\t\t\t\t\tThe nuclear receptor tailless is required for neurogenesis in the adult subventricular zone. Genes Dev 2008\n\t\t\t\t\t22\n\t\t\t\t\t18\n\t\t\t\t\t2473\n\t\t\t\t\t8\n\t\t\t\t\n\t\t\t'},{id:"B109",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZhang\n\t\t\t\t\t\t\tC. L\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZou\n\t\t\t\t\t\t\tY\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHe\n\t\t\t\t\t\t\tW\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGage\n\t\t\t\t\t\t\tF. H\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tEvans\n\t\t\t\t\t\t\tR. M\n\t\t\t\t\t\t\n\t\t\t\t\tA role for adult TLX-positive neural stem cells in learning and behaviour. Nature 2008\n\t\t\t\t\t451\n\t\t\t\t\t7181\n\t\t\t\t\t1004\n\t\t\t\t\t7\n\t\t\t\t\n\t\t\t'},{id:"B110",body:'\n\t\t\t\tMazumdar , J, O\'Brien, W. T, Johnson, R. S, LaManna, J. C, Chavez, J. C, Klein, P. S, & Simon, M. C. O2 regulates stem cells through Wnt/beta-catenin signalling. Nat Cell Biol (2010). , 12(10), 1007-13.\n\t\t\t'},{id:"B111",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tToledo\n\t\t\t\t\t\t\tE. M\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tColombres\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tInestrosa\n\t\t\t\t\t\t\tN. C\n\t\t\t\t\t\t\n\t\t\t\t\tWnt signaling in neuroprotection and stem cell differentiation. Progress in neurobiology 2008\n\t\t\t\t\t86\n\t\t\t\t\t3\n\t\t\t\t\t281\n\t\t\t\t\t96\n\t\t\t\t\n\t\t\t'},{id:"B112",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDickson\n\t\t\t\t\t\t\tD. W\n\t\t\t\t\t\t\n\t\t\t\t\tApoptotic mechanisms in Alzheimer neurofibrillary degeneration: cause or effect? J Clin Invest 2004\n\t\t\t\t\t114\n\t\t\t\t\t1\n\t\t\t\t\t23\n\t\t\t\t\t7\n\t\t\t\t\n\t\t\t'},{id:"B113",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTakashima\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNoguchi\n\t\t\t\t\t\t\tK\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSato\n\t\t\t\t\t\t\tK\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHoshino\n\t\t\t\t\t\t\tT\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tImahori\n\t\t\t\t\t\t\tK\n\t\t\t\t\t\t\n\t\t\t\t\tTau protein kinase I is essential for amyloid beta-protein-induced neurotoxicity. Proc Natl Acad Sci U S A 1993\n\t\t\t\t\t90\n\t\t\t\t\t16\n\t\t\t\t\t7789\n\t\t\t\t\t93\n\t\t\t\t\n\t\t\t'},{id:"B114",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTsai\n\t\t\t\t\t\t\tL. H\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLee\n\t\t\t\t\t\t\tM. S\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCruz\n\t\t\t\t\t\t\tJ\n\t\t\t\t\t\t\n\t\t\t\t\tCdk5, a therapeutic target for Alzheimer’s disease? Biochim Biophys Acta (2004). , 1697(1-2), 137-42\n\t\t\t'},{id:"B115",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGarrido\n\t\t\t\t\t\t\tJ. L\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGodoy\n\t\t\t\t\t\t\tJ. A\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAlvarez\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBronfman\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tInestrosa\n\t\t\t\t\t\t\tN. C\n\t\t\t\t\t\t\n\t\t\t\t\tProtein kinase C inhibits amyloid beta peptide neurotoxicity by acting on members of the Wnt pathway. Faseb J 2002\n\t\t\t\t\t16\n\t\t\t\t\t14\n\t\t\t\t\t1982\n\t\t\t\t\t4\n\t\t\t\t\n\t\t\t'},{id:"B116",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tInestrosa\n\t\t\t\t\t\t\tN. C\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAlvarez\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGodoy\n\t\t\t\t\t\t\tJ\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tReyes\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDe Ferrari\n\t\t\t\t\t\t\tG. V\n\t\t\t\t\t\t\n\t\t\t\t\tAcetylcholinesterase-amyloid-beta-peptide interaction and Wnt signaling involvement in Abeta neurotoxicity. Acta Neurol Scand Suppl 2000\n\t\t\t\t\t53\n\t\t\t\t\t9\n\t\t\t\t\n\t\t\t'},{id:"B117",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDe Ferrari\n\t\t\t\t\t\t\tG. V\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChacon\n\t\t\t\t\t\t\tM. A\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBarria\n\t\t\t\t\t\t\tM. I\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGarrido\n\t\t\t\t\t\t\tJ. L\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGodoy\n\t\t\t\t\t\t\tJ. A\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOlivares\n\t\t\t\t\t\t\tG\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tReyes\n\t\t\t\t\t\t\tA. E\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAlvarez\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBronfman\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tInestrosa\n\t\t\t\t\t\t\tN. C\n\t\t\t\t\t\t\n\t\t\t\t\tActivation of Wnt signaling rescues neurodegeneration and behavioral impairments induced by beta-amyloid fibrils. Mol Psychiatry 2003\n\t\t\t\t\t8\n\t\t\t\t\t2\n\t\t\t\t\t195\n\t\t\t\t\t208\n\t\t\t\t\n\t\t\t'},{id:"B118",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tInestrosa\n\t\t\t\t\t\t\tN\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDe Ferrari\n\t\t\t\t\t\t\tG. V\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGarrido\n\t\t\t\t\t\t\tJ. L\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAlvarez\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOlivares\n\t\t\t\t\t\t\tG. H\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBarria\n\t\t\t\t\t\t\tM. I\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBronfman\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChacon\n\t\t\t\t\t\t\tM. A\n\t\t\t\t\t\t\n\t\t\t\t\tWnt signaling involvement in beta-amyloid-dependent neurodegeneration. Neurochem Int 2002\n\t\t\t\t\t41\n\t\t\t\t\t5\n\t\t\t\t\t341\n\t\t\t\t\t4\n\t\t\t\t\n\t\t\t'},{id:"B119",body:'\n\t\t\t\tDe Ferrari, G. V, Papassotiropoulos, A, Biechele, T, Wavrant De-Vrieze, F, Avila, M. E, Major, M. B, Myers, A, Sáez, K, Henríquez, J. P, Zhao, A, Wollmer, M. A, Nitsch, R. M, Hock, C, Morris, C. M, Hardy, J, & Moon, R. T. Common genetic variation within the low-density lipoprotein receptor-related protein 6 and late-onset Alzheimer’s disease. Proc Natl Acad Sci U S A 2007\n\t\t\t\t\t104\n\t\t\t\t\t22\n\t\t\t\t\t9434\n\t\t\t\t\t9\n\t\t\t\t\n\t\t\t'},{id:"B120",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAlvarez\n\t\t\t\t\t\t\tG\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMunoz-montano\n\t\t\t\t\t\t\tJ. R\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSatrustegui\n\t\t\t\t\t\t\tJ\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAvila\n\t\t\t\t\t\t\tJ\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBogonez\n\t\t\t\t\t\t\tE\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDiaz-nido\n\t\t\t\t\t\t\tJ\n\t\t\t\t\t\t\n\t\t\t\t\tRegulation of tau phosphorylation and protection against beta-amyloid-induced neurodegeneration by lithium. Possible implications for Alzheimer’s disease. Bipolar Disord 2002\n\t\t\t\t\t4\n\t\t\t\t\t3\n\t\t\t\t\t153\n\t\t\t\t\t65\n\t\t\t\t\n\t\t\t'},{id:"B121",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCaricasole\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCopani\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCaraci\n\t\t\t\t\t\t\tF\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAronica\n\t\t\t\t\t\t\tE\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRozemuller\n\t\t\t\t\t\t\tA. J\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCaruso\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tStorto\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGaviraghi\n\t\t\t\t\t\t\tG\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTerstappen\n\t\t\t\t\t\t\tG. C\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNicoletti\n\t\t\t\t\t\t\tF\n\t\t\t\t\t\t\n\t\t\t\t\tInduction of Dickkopf-1, a negative modulator of the Wnt pathway, is associated with neuronal degeneration in Alzheimer’s brain. J Neurosci 2004\n\t\t\t\t\t24\n\t\t\t\t\t26\n\t\t\t\t\t6021\n\t\t\t\t\t7\n\t\t\t\t\n\t\t\t'},{id:"B122",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGhanevati\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMiller\n\t\t\t\t\t\t\tC. A\n\t\t\t\t\t\t\n\t\t\t\t\tPhospho-beta-catenin accumulation in Alzheimer’s disease and in aggresomes attributable to proteasome dysfunction. J Mol Neurosci 2005\n\t\t\t\t\t25\n\t\t\t\t\t1\n\t\t\t\t\t79\n\t\t\t\t\t94\n\t\t\t\t\n\t\t\t'},{id:"B123",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTakashima\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMurayama\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMurayama\n\t\t\t\t\t\t\tO\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKohno\n\t\t\t\t\t\t\tT\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHonda\n\t\t\t\t\t\t\tT\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYasutake\n\t\t\t\t\t\t\tK\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNihonmatsu\n\t\t\t\t\t\t\tN\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMercken\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYamaguchi\n\t\t\t\t\t\t\tH\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSugihara\n\t\t\t\t\t\t\tS\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWolozin\n\t\t\t\t\t\t\tB\n\t\t\t\t\t\t\n\t\t\t\t\tPresenilin 1 associates with glycogen synthase kinase-3beta and its substrate tau. Proc Natl Acad Sci U S A 1998\n\t\t\t\t\t95\n\t\t\t\t\t16\n\t\t\t\t\t9637\n\t\t\t\t\t41\n\t\t\t\t\n\t\t\t'},{id:"B124",body:'\n\t\t\t\tZhang, Z, Hartmann, H, Do, V. M, Abramowski, D, Sturchler-Pierrat, C, Staufenbiel, M, Sommer, B, van de Wetering, M, Clevers, H, Saftig, P, De Strooper, B, He, X, & Yankner B. A. Destabilization of beta-catenin by mutations in presenilin-1 potentiates neuronal apoptosis. Nature 1998\n\t\t\t\t\t395\n\t\t\t\t\t6703\n\t\t\t\t\t698\n\t\t\t\t\t702\n\t\t\t\t\n\t\t\t'},{id:"B125",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMoon\n\t\t\t\t\t\t\tR. T\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKohn\n\t\t\t\t\t\t\tA. D\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDe Ferrari\n\t\t\t\t\t\t\tG. V\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKaykas\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\tWNT and beta-catenin signalling: diseases and therapies. Nat Rev Genet 2004\n\t\t\t\t\t5\n\t\t\t\t\t9\n\t\t\t\t\t691\n\t\t\t\t\t701\n\t\t\t\t\n\t\t\t'},{id:"B126",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRosi\n\t\t\t\t\t\t\tM. C\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLuccarini\n\t\t\t\t\t\t\tI\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGrossi\n\t\t\t\t\t\t\tC\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFiorentini\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSpillantini\n\t\t\t\t\t\t\tM. G\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPrisco\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tScali\n\t\t\t\t\t\t\tC\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGianfriddo\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCaricasole\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTerstappen\n\t\t\t\t\t\t\tG. C\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCasamenti\n\t\t\t\t\t\t\tF\n\t\t\t\t\t\t\n\t\t\t\t\tIncreased Dickkopf-1 expression in transgenic mouse models of neurodegenerative disease. J Neurochem 2010\n\t\t\t\t\t112\n\t\t\t\t\t6\n\t\t\t\t\t1539\n\t\t\t\t\t51\n\t\t\t\t\n\t\t\t'},{id:"B127",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCaruso\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMotolese\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tIacovelli\n\t\t\t\t\t\t\tL\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCaraci\n\t\t\t\t\t\t\tF\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCopani\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNicoletti\n\t\t\t\t\t\t\tF\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTerstappen\n\t\t\t\t\t\t\tG. C\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGaviraghi\n\t\t\t\t\t\t\tG\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCaricasole\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\tInhibition of the canonical Wnt signaling pathway by apolipoprotein E4 in PC12 cells. J Neurochem 2006\n\t\t\t\t\t98\n\t\t\t\t\t2\n\t\t\t\t\t364\n\t\t\t\t\t71\n\t\t\t\t\n\t\t\t'},{id:"B128",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMagdesian\n\t\t\t\t\t\t\tM. H\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCarvalho\n\t\t\t\t\t\t\tM. M\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMendes\n\t\t\t\t\t\t\tF. A\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSaraiva\n\t\t\t\t\t\t\tL. M\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJuliano\n\t\t\t\t\t\t\tM. A\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJuliano\n\t\t\t\t\t\t\tL\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGarcia-abreu\n\t\t\t\t\t\t\tJ\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFerreira\n\t\t\t\t\t\t\tS. T\n\t\t\t\t\t\t\n\t\t\t\t\tAmyloid-beta binds to the extracellular cysteine-rich domain of Frizzled and inhibits Wnt/beta-catenin signaling. J Biol Chem 2008\n\t\t\t\t\t283\n\t\t\t\t\t14\n\t\t\t\t\t9359\n\t\t\t\t\t68\n\t\t\t\t\n\t\t\t'},{id:"B129",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAlvarez\n\t\t\t\t\t\t\tA. R\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGodoy\n\t\t\t\t\t\t\tJ. A\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMullendorff\n\t\t\t\t\t\t\tK\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOlivares\n\t\t\t\t\t\t\tG. H\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBronfman\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tInestrosa\n\t\t\t\t\t\t\tN. C\n\t\t\t\t\t\t\n\t\t\t\t\tWnt-3a overcomes beta-amyloid toxicity in rat hippocampal neurons. Exp Cell Res 2004\n\t\t\t\t\t297\n\t\t\t\t\t1\n\t\t\t\t\t186\n\t\t\t\t\t96\n\t\t\t\t\n\t\t\t'},{id:"B130",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPurro\n\t\t\t\t\t\t\tS. A\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDickins\n\t\t\t\t\t\t\tE. M\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSalinas\n\t\t\t\t\t\t\tP. C\n\t\t\t\t\t\t\n\t\t\t\t\tThe secreted Wnt antagonist Dickkopf-1 is required for amyloid beta-mediated synaptic loss. J Neurosci 2010\n\t\t\t\t\t32\n\t\t\t\t\t10\n\t\t\t\t\t3492\n\t\t\t\t\t8\n\t\t\t\t\n\t\t\t'},{id:"B131",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBallard\n\t\t\t\t\t\t\tC\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGauthier\n\t\t\t\t\t\t\tS\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCorbett\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBrayne\n\t\t\t\t\t\t\tC\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAarsland\n\t\t\t\t\t\t\tD\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJones\n\t\t\t\t\t\t\tE\n\t\t\t\t\t\t\n\t\t\t\t\tAlzheimer’s disease. Lancet 2011\n\t\t\t\t\t377\n\t\t\t\t\t9770\n\t\t\t\t\t1019\n\t\t\t\t\t31\n\t\t\t\t\n\t\t\t'},{id:"B132",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChurcher\n\t\t\t\t\t\t\tI\n\t\t\t\t\t\t\n\t\t\t\t\tTau therapeutic strategies for the treatment of Alzheimer’s disease. Curr Top Med Chem 2006\n\t\t\t\t\t6\n\t\t\t\t\t6\n\t\t\t\t\t579\n\t\t\t\t\t95\n\t\t\t\t\n\t\t\t'},{id:"B133",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHooper\n\t\t\t\t\t\t\tC\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKillick\n\t\t\t\t\t\t\tR\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLovestone\n\t\t\t\t\t\t\tS\n\t\t\t\t\t\t\n\t\t\t\t\tThe GSK3 hypothesis of Alzheimer’s disease. J Neurochem 2008\n\t\t\t\t\t104\n\t\t\t\t\t6\n\t\t\t\t\t1433\n\t\t\t\t\t9\n\t\t\t\t\n\t\t\t'},{id:"B134",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTakashima\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNoguchi\n\t\t\t\t\t\t\tK\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMichel\n\t\t\t\t\t\t\tG\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMercken\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHoshi\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tIshiguro\n\t\t\t\t\t\t\tK\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tImahori\n\t\t\t\t\t\t\tK\n\t\t\t\t\t\t\n\t\t\t\t\tExposure of rat hippocampal neurons to amyloid beta peptide (25-35) induces the inactivation of phosphatidyl inositol-3 kinase and the activation of tau protein kinase I/glycogen synthase kinase-3 beta. Neurosci Lett 1996\n\t\t\t\t\t203\n\t\t\t\t\t1\n\t\t\t\t\t33\n\t\t\t\t\t6\n\t\t\t\t\n\t\t\t'},{id:"B135",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTakashima\n\t\t\t\t\t\t\tA\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHonda\n\t\t\t\t\t\t\tT\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYasutake\n\t\t\t\t\t\t\tK\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMichel\n\t\t\t\t\t\t\tG\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMurayama\n\t\t\t\t\t\t\tO\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMurayama\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tIshiguro\n\t\t\t\t\t\t\tK\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYamaguchi\n\t\t\t\t\t\t\tH\n\t\t\t\t\t\t\n\t\t\t\t\tActivation of tau protein kinase I/glycogen synthase kinase-3beta by amyloid beta peptide (25-35) enhances phosphorylation of tau in hippocampal neurons. Neurosci Res 1998\n\t\t\t\t\t31\n\t\t\t\t\t4\n\t\t\t\t\t317\n\t\t\t\t\t23\n\t\t\t\t\n\t\t\t'},{id:"B136",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPei\n\t\t\t\t\t\t\tJ. J\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBraak\n\t\t\t\t\t\t\tE\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBraak\n\t\t\t\t\t\t\tH\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGrundke-iqbal\n\t\t\t\t\t\t\tI\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tIqbal\n\t\t\t\t\t\t\tK\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWinblad\n\t\t\t\t\t\t\tB\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCowburn\n\t\t\t\t\t\t\tR. F\n\t\t\t\t\t\t\n\t\t\t\t\tDistribution of active glycogen synthase kinase 3beta (GSK-3beta) in brains staged for Alzheimer disease neurofibrillary changes. J Neuropathol Exp Neurol 1999\n\t\t\t\t\t58\n\t\t\t\t\t9\n\t\t\t\t\t1010\n\t\t\t\t\t9\n\t\t\t\t\n\t\t\t'},{id:"B137",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHernandez\n\t\t\t\t\t\t\tF\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBorrell\n\t\t\t\t\t\t\tJ\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGuaza\n\t\t\t\t\t\t\tC\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAvila\n\t\t\t\t\t\t\tJ\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLucas\n\t\t\t\t\t\t\tJ. J\n\t\t\t\t\t\t\n\t\t\t\t\tSpatial learning deficit in transgenic mice that conditionally over-express GSK-3beta in the brain but do not form tau filaments. J Neurochem 2002\n\t\t\t\t\t83\n\t\t\t\t\t6\n\t\t\t\t\t1529\n\t\t\t\t\t33\n\t\t\t\t\n\t\t\t'},{id:"B138",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLucas\n\t\t\t\t\t\t\tJ. J\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHernandez\n\t\t\t\t\t\t\tF\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGomez-Ramos\n\t\t\t\t\t\t\tP\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMoran\n\t\t\t\t\t\t\tM. A\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHen\n\t\t\t\t\t\t\tR\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAvila\n\t\t\t\t\t\t\tJ\n\t\t\t\t\t\t\n\t\t\t\t\tDecreased nuclear beta-catenin, tau hyperphosphorylation and neurodegeneration in GSK-3beta conditional transgenic mice. EMBO J (2001). , 20(1-2), 27-39.\n\t\t\t'},{id:"B139",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLi\n\t\t\t\t\t\t\tH. L\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWang\n\t\t\t\t\t\t\tH. H\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLiu\n\t\t\t\t\t\t\tS. J\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDeng\n\t\t\t\t\t\t\tY. Q\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZhang\n\t\t\t\t\t\t\tY. J\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTian\n\t\t\t\t\t\t\tQ\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWang\n\t\t\t\t\t\t\tX. C\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChen\n\t\t\t\t\t\t\tX. Q\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYang\n\t\t\t\t\t\t\tY\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZhang\n\t\t\t\t\t\t\tJ. Y\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWang\n\t\t\t\t\t\t\tQ\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tXu\n\t\t\t\t\t\t\tH\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLiao\n\t\t\t\t\t\t\tF. F\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWang\n\t\t\t\t\t\t\tJ. Z\n\t\t\t\t\t\t\n\t\t\t\t\tPhosphorylation of tau antagonizes apoptosis by stabilizing beta-catenin, a mechanism involved in Alzheimer’s neurodegeneration. Proc Natl Acad Sci U S A 2007\n\t\t\t\t\t104\n\t\t\t\t\t9\n\t\t\t\t\t3591\n\t\t\t\t\t6\n\t\t\t\t\n\t\t\t'},{id:"B140",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGarcia-Alloza\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRobbins\n\t\t\t\t\t\t\tE. M\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZhang-nunes\n\t\t\t\t\t\t\tS. X\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPurcell\n\t\t\t\t\t\t\tS. M\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBetensky\n\t\t\t\t\t\t\tR. A\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRaju\n\t\t\t\t\t\t\tS\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPrada\n\t\t\t\t\t\t\tC\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGreenberg\n\t\t\t\t\t\t\tS. M\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBacskai\n\t\t\t\t\t\t\tB. J\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFrosch\n\t\t\t\t\t\t\tM. P\n\t\t\t\t\t\t\n\t\t\t\t\tCharacterization of amyloid deposition in the APPswe/PS1dE9 mouse model of Alzheimer disease. Neurobiol Dis 2006\n\t\t\t\t\t24\n\t\t\t\t\t3\n\t\t\t\t\t516\n\t\t\t\t\t24\n\t\t\t\t\n\t\t\t'},{id:"B141",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tToledo\n\t\t\t\t\t\t\tE. M\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tInestrosa\n\t\t\t\t\t\t\tN. C\n\t\t\t\t\t\t\n\t\t\t\t\tActivation of Wnt signaling by lithium and rosiglitazone reduced spatial memory impairment and neurodegeneration in brains of an APPswe/PSEN1DeltaE9 mouse model of Alzheimer’s disease. Molecular psychiatry 2010\n\t\t\t\t\t15\n\t\t\t\t\t3\n\t\t\t\t\t272\n\t\t\t\t\t85\n\t\t\t\t\n\t\t\t'},{id:"B142",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHu\n\t\t\t\t\t\t\tY. S\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tXu\n\t\t\t\t\t\t\tP\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPigino\n\t\t\t\t\t\t\tG\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBrady\n\t\t\t\t\t\t\tS. T\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLarson\n\t\t\t\t\t\t\tJ\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLazarov\n\t\t\t\t\t\t\tO\n\t\t\t\t\t\t\n\t\t\t\t\tComplex environment experience rescues impaired neurogenesis, enhances synaptic plasticity, and attenuates neuropathology in familial Alzheimer’s disease-linked APPswe/PS1DeltaE9 mice. FASEB J 2010\n\t\t\t\t\t24\n\t\t\t\t\t6\n\t\t\t\t\t1667\n\t\t\t\t\t81\n\t\t\t\t\n\t\t\t'},{id:"B143",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCerpa\n\t\t\t\t\t\t\tW\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFarias\n\t\t\t\t\t\t\tG. G\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGodoy\n\t\t\t\t\t\t\tJ. A\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFuenzalida\n\t\t\t\t\t\t\tM\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBonansco\n\t\t\t\t\t\t\tC\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tInestrosa\n\t\t\t\t\t\t\tN. C\n\t\t\t\t\t\t\n\t\t\t\t\tWnt-5a occludes Abeta oligomer-induced depression of glutamatergic transmission in hippocampal neurons. Mol Neurodegener (2010). , 5, 3.\n\t\t\t'},{id:"B144",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSelkoe\n\t\t\t\t\t\t\tD. J\n\t\t\t\t\t\t\n\t\t\t\t\tAlzheimer’s disease is a synaptic failure. Science (New York, N.Y.) (2002). 298\n\t\t\t\t\t5594\n\t\t\t\t\t789\n\t\t\t\t\t91\n\t\t\t\t\n\t\t\t'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Nibaldo C. Inestrosa ",address:null,affiliation:'
Center for Aging and Regeneration (CARE), Department of Cell and Molecular Biology, Faculty of Biological Sciences, Pontifical Catholic University of Chile, Santiago, Chile
Center for Aging and Regeneration (CARE), Department of Cell and Molecular Biology, Faculty of Biological Sciences, Pontifical Catholic University of Chile, Santiago, Chile
'}],corrections:null},book:{id:"3148",title:"Trends in Cell Signaling Pathways in Neuronal Fate Decision",subtitle:null,fullTitle:"Trends in Cell Signaling Pathways in Neuronal Fate Decision",slug:"trends-in-cell-signaling-pathways-in-neuronal-fate-decision",publishedDate:"March 27th 2013",bookSignature:"Sabine Wislet-Gendebien",coverURL:"https://cdn.intechopen.com/books/images_new/3148.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"65329",title:"Dr.",name:"Sabine",middleName:null,surname:"Wislet",slug:"sabine-wislet",fullName:"Sabine Wislet"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},chapters:[{id:"42065",title:"Role of TGF-β Signaling in Neurogenic Regions After Brain Injury",slug:"role-of-tgf-signaling-in-neurogenic-regions-after-brain-injury",totalDownloads:4376,totalCrossrefCites:3,signatures:"Sonia Villapol, Trevor T. Logan and Aviva J. 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1. Introduction
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Pectin is the major constituent of all plants and makes up approximately two-third of the dry mass of plant primary cell walls. It provides structural integrity, strength, and flexibility to the cell wall and acts as barrier to the external environment [1]. Pectin is also a natural component of all omnivorous diet and is an important source of dietary fiber. Due to the resistant in digestive system and lack of pectin digestive enzymes, human beings are not able to digest pectin directly but microorganism present in large intestine can easily assimilate the pectin and convert it into soluble fibers. These oligosaccharides promote beneficial microbiota in gut and also help in lipid and fat metabolism, glycemic regulation, etc. [2]. Being complex and highly diverse in structure, role of pectin is not only limited to the biological and physiological functions, but it has tremendous potential and contributes substantially in other applications ranging from food processing to pharmaceuticals. Pectin is a water-soluble fiber and used in various food as emulsifier, stabilizer, gelling, and thickening agent.
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Commercial pectins are extracted from citrus and apple fruit. On the basis of dry mass, apple pomace contains 10–15% pectin, whereas citrus peel possesses 20–30% pectin. However, pectin has also been extracted in higher amount from several other fruits and their by-products, such as sunflower head, mango peal, soybean hull [3], passion fruit peel [4], sugar beet pulp [5], Akebia trifoliata peel [6], peach pomace [7], banana peel [8], chickpea husk [9], and many more [10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23]. Table 1 summarizes the different types of pectin extracted from various horticultural crops. But detection and extraction of pectin in higher concentration is not sufficient to qualify that fruit as a source of commercial pectin because of the structural variation and modification in side-chain sugars, and also that pectin from different sources has different gelling properties.
Pectin is a highly complex plant cell wall polysaccharide that plays a significant role in plant growth and development. It is predominantly present in fruits and vegetables and constitutes approximately 35–40% of the primary cell wall in all the dicot plants [24]. The composition and structure of pectin is influenced by the developmental stages of plants [25, 26]. Structural analysis of pectin revealed that it is a polymer comprised of chain-like configuration of approximately 100–1000 saccharide units; therefore, it does not possess a defined structure. In general, pectin is illustrated as a heteropolysaccharide of three components namely, homogalacturonan (HG), rhamnogalacturonan-I (RGI), and rhamnogalacturonan-II (RGII) [28, 29]. The Backbone structure may branch with other neutral sugar chains such as arabinan, xylogalacturonan (XGA), arabinogalactan I (AG-I), and arabinogalactan II (AG-II).
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Homogalacturonan (HG) is a polymer of galacturonic acid (GalA), in which Gal A residues are linked together by α-1-4 glycosidic bond and the number of GalA residues in HG may vary from 72 to 100% depending on the source of pectin [30]. For instance, the HG backbone of cashew apple pectin, C. maxima pectin, sunflower pectin, citrus pectin, comprises of 69.9–85%, 71–75%, 77–85%, 80–95%, GalA residues, respectively. Amaranth pectin contains more than 80% GalA residues in HG backbone structure. Furthermore, it was also observed that HG may be methoxy-esterified at C-6 and/or O-acetylated at the O-2 and/or O-3. Some exception has also been reported in the detailed structural analysis of HG region of pectin such as C-3 substitution of the galacturonic acids of HG with xylose in pea, apple, carrot, duck weed, etc. [31], and C-2 or C-3 with apiose in duck weeds (Lemna minor) [32]. HG is susceptible to both mechanical and enzymatic deesterification and degradation.
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Rhamnogalacturonan I represents approximately 20–35% of the pectin polysaccharides. It is the highly branched and heterogeneous polysaccharide which is characterized as repeating units of α-(1 → 2)-linked rhamnose and α-(1 → 4)-linked GalA residues. It can be O-acetylated at O-2 and/or O-3 positions of GalA residues [33, 34]. Pectin from citrus peels, mung bean, kidney bean, apple fruit, and flax hypocotyls has been reported 100% methyl esterified in the RGI region [35, 36]. The composition of RGI varies in pectin extracted from different sources. In sugar beet pectin, 80 repeating units of [→2] –α-L-Rha-(1–4)- α-D-GalA-(1→) comprised the backbone of rhamnogalacturonan I (RG-I), whereas citrus pectin contains only 15–40 repeating units [37]. The polymeric side chains of galactans and arabinans are substituted at the O-4 position of RG-I backbone. Arabinogalactan I (AG-I) and arabinogalactan II (AG-II) are also reported to be present as polymeric side chains [38, 39, 40]. The side chains are often referred to as “hairs” and believed to play an important role in pectin functionality. The loss of side chains may increase the solubility of the pectin [41]. PGI is prone to enzymatic depolymerization. However, protease and acid-catalyzed cleavage of RGI has also been reported [28, 42, 43].
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The highly conserved polysaccharide of pectin is rhamnogalacturonan II which constitutes about 10% of the pectin polymer [44]. This polysaccharide is made up of (1 → 4)-linked-α-D-GalA units containing 12 monosaccharide such as apiose, acetic acid, 3-deoxy-manno-2-octulosonic acid (KDO), and 3-deoxy-lyxo-2-heptulosaric acid (DHA) as side chains [30, 39]. GalA present in backbone of rhamnogalacturonan II (RG-II) may be methyl esterified at the C-6 position. The percentage of esterified GalA and acetylated groups in HG chain is termed as the DE and DAc, respectively. It is proposed that in the early developmental stages of plants, highly esterified pectin is formed that undergoes some deesterification in the cell wall or middle lamella. In general, tissue pectin ranges from 60 to 90% DE [45]. Both the DE and the DAc of pectin may vary depending on the method of extraction and plant origin [30, 46]. The functional properties of the pectin are determined by the amount and the distribution of esterified GalA residues in the linear backbone. Presence and distribution of esterified and nonmethylated GalA in pectin define the charge on pectin molecules. Based on their degree of esterification (DE), pectins are classified as high methoxy pectins (HMP) or low methoxy pectins (LMP). DE values of HM pectin range from 60 to 75%, whereas pectin with 20–40% of DE is referred as LM pectin. It was also observed that solubility, viscosity, and gelation properties of pectin are correlated and highly dependent on structural features [47, 48]. Pectin and monovalent salts of pectins are generally soluble in water but di- and trivalent ions are insoluble. The solubility of pectin in water increases with decrease in polymer size and increase in methoxy contents. Pectin powder gets hydrated very fast in water and forms clumps. The solubility of these clumps is very slow. As the pectin molecules come in contact with water, deesterification and depolymerization of pectins start spontaneously. The rate of decomposition of pectin depends on pH and temperature of the solution. As the pH of the solution decreased, with elevated temperature, ionization of carboxylate groups also reduced, which suppresses the hydration and repulsion between the polysaccharide molecules and results in the association of molecules in the form of gels. During thermal processing, solubilization of pectin is affected by β-elimination which depolymerized the pectin molecule and reduced its chain length. Small polymers have poor affinity with cell wall framework and solubilize easily. However, preheating, as well as reduced moisture contents in thermal processing, adversely affects the solubility of pectin in water [49, 50].
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3. Pectin as food emulsifier
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Food additives that are used in food processing to blend two immiscible liquids to produce a desirable product are known as food emulsifier or emulgent. These additives act as surface-active agents on the border of immiscible layers and reduce oil crystallization and prevent water separation. Emulsifiers are used in large number of food products such as ice creams, low-fat spreads, yoghurts, margarine, salad dressings, salty spreads, bakery products, and many other creamy sauces, to keep them in stable emulsion [27]. Emulsifiers increase the whip-ability of batters, enhance mouthfeel of the products, and improve texture and shape of the dough. Moreover, emulsions also help to encapsulate the bioactives [51]. Based on the disperse phase, there are two types of emulsion: oil in water (O/W) and water in oil (W/O). Milk, mayonnaise, dressings, and various beverages are some examples of O/W emulsion, whereas butter and margarine are the typical examples of W/O emulsion. Progress in hydrocolloid chemistry has resulted in the development of multitype emulsion such as O/W/O and O/W/O type emulsion (Figure 1). These emulsions are very important for fat reduction or encapsulation of bioactives and are used in preparation and stabilization of various low-fat creams, seasoning, and flavoring of sauces [52].
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Figure 1.
Types of emulsions.
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Commonly used emulsifiers in food processing are (i) small-molecular surfactant such as lectithins, derivatives of mono- and diglycerides prepared by mixing edible oils with glycerin or ethylene oxide, fatty acid derivatives such as glycol esters, sorbitan esters, polysorbates and (ii) macromolecular emulsifiers that include proteins and plant-based polymers such as soy polysaccharide, guar gum, modified starch, pectin, etc. [53]. As far as the properties of food emulsifier are concern, a good emulsifier should be low in molecular weight, capable to reduce the surface tension rapidly at interface, and should be soluble in continuous phase [54]. Research on food additives revealed the adverse effect of synthetic food additives on human being. Chassaing et al. found that polysorbate 80(P80) or carboxy methyl cellulose (CMC) had adverse effects on gut microbiota and their continuous use triggered the weight gain and metabolic syndrome after 12 weeks of administration in mouse [55]. A recent research carried out on mice shows that regular use of P80 and CMC triggers low-grade intestinal inflammation which may ultimately lead to the development of colon cancer [56]. Therefore, safety issues with the synthetic food additives and consumer’s demand for all natural food ingredients have necessitated the use of plant-based emulsifiers and stabilizers in food.
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Pectin is a natural hydrocolloid which exhibits wide spectrum of functional properties. Because of the gelling ability of pectin, it is used as viscosity enhancer. During emulsification process, pectin molecules adsorb at the fine oil droplets from at O/W interface and protect the droplet from coalescing with adjacent drops (short-term stability). The quality of emulsifier is defined by its ability to provide long-term stability against flocculation and coalescence [27]. Figure 2 depicts the stages in long-term emulsion formation using pectin as emulgent. When the viscosity of the continuous phase is increased, the movements of oil droplets become restricted which improves the shelf life of emulsion [57]. In the past decade, some pectin has also been reported to exhibit surface active behavior in oil-water interface and thereby stabilizing the fine oil droplets in emulsion [42, 58]. These functions of pectin are determined by its source, structural modification during processing, distribution of functional groups in pectin backbone, and also by various extrinsic factors such as pH, temperature, ionic strength, cosolute concentration, etc. The emulsification or surface active properties of pectin, i.e., formation of fine oil droplets, are mainly contributed due to the high hydrophobicity of protein residue present in pectin [46, 59] and also by hydrophobic nature of acetyl, methyl, and feruloyl esters [42, 60], whereas emulsion-stabilizing ability is attributed to the carbohydrate moieties and their conformational features [61].
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Figure 2.
Emulsion formation and stabilization using polymer as emulgent.
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3.1 Mechanism of emulsion formation and stabilization
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The mechanism of emulsion formation is shown in Figure 3. Different models explain the emulsion formation as covalently bound protein moieties in pectin are adsorbed onto the oil-water interface [46], form anchor points at the interface, and reduce the interfacial tension while the charged carbohydrate units extend into the aqueous phase [62] and stabilize by steric and viscosity effects in the aqueous phase(Figure 3a). Now, it is a well-established fact that pectin from different source shows variability in structure and protein contents. Leroux et al. identified many anchor points in sugar beet pectin (SBP) molecules [46], and proposed a loop-and-tail model (Figure 3b). According to the authors, only a limited amount of protein is adsorbed at the oil surface and acts as main moiety in the stabilization of the emulsion. This model was further confirmed by Siew and others [62]. The study was carried out to measure the thickness of the adsorbed SBP on oil-water interface layer, proposed a multilayer adsorption model (Figure 3c). Electrostatic interactions between the positively charged protein moiety and the negatively charged carbohydrate moiety were also reported.
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Figure 3.
Different models showing pectin adsorption at oil/water interface during emulsion formation.
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Pectin O/W emulsion is generally stabilized through steric and electrostatic interaction. The carbohydrate moieties and neutral sugar side chains of RG I region of pectin confer the stability to the pectin emulsions through steric properties of the adsorbed polymers, when pectin is used as monoemulsifiers. In addition, pectin reversible association with galactan/arabinogalactan prior to emulsification also improves the emulsion stability [42, 63]. Electrostatic stabilization of emulsion is ascribed to sugar moieties and structural features of the HG units of pectin. If the pH of dispersion medium is above 3.5, nonmethylated carboxylic group of HG region gets ionized and confers charge on the pectin surface. Interaction of an ionic surfactant with oil droplets results in electrostatic stabilization [64]. Pectin viscosity also plays an important role in controlling the emulsion stability. HG region-rich pectin shows higher intrinsic viscosity ([η]); therefore, HG and RG ratio of pectin and molecular interactions that improve the intrinsic viscosity ([η]) of pectin solution also contributes in shelf life of emulsion [65, 66]. It has also observed that structural features of pectin such as pectin protein content, molecular mass, and presence of ferulic acid, and acetyl group in carbohydrate moieties of pectin also affect pectin’s emulsifying and emulsion stabilization properties [15]. Williams et al. showed that ferulic acid-rich pectin did not show significant difference in emulsifying ability of pectin when compared with pectin poor in ferulic acid [67]. Digestion of sugar beet pectin(SBP) with acidic proteases resulted in formation of larger size of oil droplet, lower creaming stability, and loss of emulsifying activity of SBP which confirms that protein contents of SBP play an important role in emulsifying ability of the polymer [42]. Nevertheless, in other research, it was also found that protein-rich fractions of SBP did not necessarily displayed better emulsifying ability; therefore, it was concluded that both protein with carbohydrate moiety together help in controlling emulsifying ability of SBP. Castellani et al. further suggest that both the carbohydrate and protein moieties function together as unit and affect the hydrophilic-hydrophobic equilibrium of the SBP molecule [68]. Therefore, when SBP is digested with proteases or other enzyme, a single moiety may function differently. Furthermore, it was also proposed that protein folding may also mask the hydrophobic effect of protein and thus affect the overall properties of the polymers [69].
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Molecular weight of pectin has also been reported to affect the emulsifying capacity of pectin. Pectin with low molecular weight was more efficient in stabilizing small emulsion droplets than high-molecular weight pectin. However, very small size of citrus pectin had negative effect on emulsion-stabilizing ability of pectin. It could be due to the poor steric stabilization of depolymerized polymer [59].
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3.2 Pectin-containing emulsion-based food
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Emulsion-based food products can be defined as a network of pectin-protein molecules entrapping the oil droplet in between. Nowadays, a large number of pectin- and polysaccharide-based emulsified low-fat dairy products, meat products, spreads or desserts, bakery products, sauces, etc., are available in market. Low-fat and low-cholesterol mayonnaise, low-fat cottage cheese, low-fat drinking yogurt, and flavored oil-containing acidified milk drinks are the few examples of pectin-based emulsified products. These products are prepared by replacing full-fat milk from skimmed milk, emulsified oil, and whey proteins [70, 71]. A low-fat cheese was prepared using skimmed milk and water-in-oil-in-water (W1/O/W2) emulsified canola oil. Different emulsifiers such as amidated low-methoxyl pectins (LMP), gum arabic (GA), carboxymethylcellulose (CMC), and combinations of GA-CMC or GA-LMP were used to stabilize the emulsion. Textural characteristics and sensory evaluation of low-fat cheese show that polymers used to stabilize the emulsion affected both microcrystalline structure and organoleptic properties. The cheese prepared using GA and LMP was almost similar in textural characteristics to the full-fat milk cheese [72]. In another study, Liu et al. compared the textural and structural features and sensory quality of full-fat and low-fat cheese analogs prepared with or without the incorporation of pectin [71]. Microstructure analysis using scanning electron microscopy revealed that full-fat cheese was denser and contained higher concentration of fat globules than low-fat cheese made with or without pectin. Comparison within the low-fat cheese analogs showed clear difference in their hardness, gumminess, chewiness, and adhesiveness. Addition of pectin had positive effect on textural and sensory attribute and scored better in mouthfeel also.
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Low-fat (Lf) mayonnaise was prepared by partial replacement of egg yolk and incorporation of pectin as emulsifier [73, 74]. Pectin weak gel, pectin microencapsulation, and whey protein isolate were used in preparation of low-fat (Lf) mayonnaise. Physicochemical and sensory properties of Lf mayonnaise were compared with full-fat (Ff) mayonnaise; Lf mayonnaise had low energy and more water contents than Ff. Textural features and rheological properties of the Lf and Ff mayonnaise were similar and both displayed thixotropic shear thinning behavior and categorized as weak gels. Moreover, Lf mayonnaise prepared using pectin had better acceptability than whey protein incorporation [75]. Emulsified oil is used as an effective delivery system of active compound in functional foods, and also serves as milk fat replacer in fat-free dairy products. To improve the nutritional value of food, low-fat dairy products are produced, whereas saturated milk fat is generally replaced with emulsified-unsaturated vegetable oils [76].
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In recent year, pectin in combination with inulin has been reported to prepare low-fat meat batter. Méndez-Zamora et al. studied the effect of substitution of animal fat with different formulations of pectin and inulin on chemical composition, textural, and sensory properties of frankfurter sausages [77]. Finding of the research showed that fracturability, gumminess, and chewiness of the low-fat sauces were slightly lower than those of the control. However, addition of 15% inulin improves the sensory properties. In a similar work, replacement of pork back fat with 15% pectin and 15% inulin was found effective in maintaining the physicochemical properties and emulsion stability of the low-fat meat batter [78].
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4. Pectin as gelling agent
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The use of pectin in food products as a gelling agent is a long tradition. Later on, it was discovered that pectin forms different types of viscoelastic solution under suitable conditions. This property of pectin is commercially exploited in preparation of jams, jellies, and marmalades. Rheological behaviors of pectin depend on pectin source, its degree of methylation, distribution of nonmethylated GalA unit on pectin backbone, and degree of acetylation, and also on various extrinsic factors such as temperature, pH, concentration, and presence of divalent ions. At a constant pH, the setting time of pectin increases with decreasing DM and degree of blockiness (DB) in the absence of bivalent ions [79]. Therefore, on the basis of gelling process, pectin is classified as rapid, medium, and slow set pectin [80].
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Gelling process of pectin and its stabilization follows different mechanisms for different types of pectin. HMP form gels in a narrow pH range (2.0–3.5) in the presence of sucrose at a concentration higher than 55% w/v in medium. During the gelatin process of HMP, junction zones are formed due to the cross-linking of two or more pectin molecules. These junctions are stabilized by weak molecular interaction such as hydrogen and hydrophobic bonds between polar and nonpolar methyl-esterified groups and require high sugar concentration and low pH [81]. These gels are thermally reversible. LMP can form gel over a wide pH range (2.0–6.0) independent of sucrose, but requires divalent ion, such as calcium [82, 83]. LMP follow the eggbox model for its gelation, where positively charged calcium ions (Ca2+) are entrapped in between the negatively charged carboxylic group of pectin. The zigzag network of Ca2+ ion and GalA molecules looks like eggbox, and therefore, model is named as eggbox model [80]. These gels are stabilized by electrostatic bonds. In the presence of Ca2+, calcium bridges are formed with pectin molecules that make the solution more viscous. At the higher pH, the ionic strength of the solution is increased and thus more Ca2+ is needed for gelation. In case of highly acetylated pectin such as sugar beet, acetyl groups cause steric hindrances and interfere with the Ca2+ ion and GalA bond formation, thus preventing gel formation. Kuuva et al. [84] reported that enzymatic modification in pectin structure, i.e., removal of acetyl groups using α-arabinofuranosidase (α-Afases) and acetyl esterase enzymes, can improve the gelling property of acetylated pectin.
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HMP are generally used in preparation of standard jams where sugar contents are above 55%, high-quality, tender confectionary jellies, fruit pastes, etc. LMP do not require sugar for its gelatin and therefore preferred choice for the production of low-calorie food products such as milk desserts, jams, jellies, and preserves, [28, 85]. LM pectins are more stable in low pH and high temperature conditions as compare to HM pectins and can be stored for more than a year.
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5. Pectin in food packaging
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Food packaging is one of the fastest growing segments of food industry. Traditionally, packaging system was limited to the containers and packaging material to transport the food items from manufacturer to the retail market and then to the consumers. Such type of packaging was unable to contribute in the extension of the shelf life and maintenance of the quality of the products. Due to the globalization of food market and increasing demand of shelf-stable processed food that retains the natural properties of food, the need of functional/active packaging material is increasing. To meet the industrial demand, a number of polymers are being synthesized and used in food packaging because of their flexibility, versatility, and cost effectiveness. Although, synthetic materials are able to fulfill all the industrial needs and keep food fresh and safe by protecting them from abiotic factors such as moisture, heat, oxygen, unpleasant odor, and biotic components such as micro- and macroorganisms. But, disposal of nonbiodegradable packaging material is a serious problem which poses a threat to the environment. Therefore, more research has been focused on the development of biodegradable packaging for food packaging applications using poly(lactic acid) (PLA), poly(hydroxyalkanoates) (PHAs), starch, etc. [86]. Among all the natural polymers, polysaccharides are gaining more attention as they are versatile in nature and easily available in relatively low cost.
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A variety of natural polysaccharides, such as pectin, chitosan derivatives, alginate, cellulose, seaweed extract, and starch are usually used in the preparation of edible films and coatings [87]. Pectin is one of the most significant renewable natural polymers which are the main component of all the biomass and ubiquitous in nature. Being flexible in nature, pectin and its derivatives are used in many biodegradable packaging materials that serve as moisture, oil, and aroma barrier, reduce respiration rate and oxidation of food [88]. Pectin along with food grade emulsifiers is also used in the preparation of edible films. These films are used in fresh and minimally processed, fruits and vegetables, foods and food products as pectin is the main component of the omnivorous diet and can be metabolized. Edible coating protects the nutritional properties of the food and also saves highly perishable food from the enzymatic browning, off-flavor development, aroma loss, retards lipid migration, and reduces pathogen attack during storage.
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At low pH, LM pectins are cross-linked with calcium cations and form hard gels. These gels have highly stable structure and act as water barriers. Because of these properties, LM pectin films are used as edible coatings [88, 89]. Extension of shelf life of avocado fruits was also reported to over a month at 10°C by using edible pectin films. It was found that when avocados were coated with edible pectin films and stored at 10°C, rate of oxygen absorption and rate of respiration decreased which results in delaying of texture and color change of fruits [90]. Oms-Oliu et al. used calcium chloride and sunflower oil cross-linked with LM pectin films onto fresh-cut melon to see the effect on extension of shelf life of cut fruits [91]. It was observed that edible pectin films maintained the initial firmness, decrease the wounding stress of fresh-cut fruits, and prevent the dehydration during storage up to 15 days at 4°C but could not reduce the microbial growth onto the fresh melon. It has been observed that to reduce the respiration rate and to prevent the off-flavor development, different pectin and emulsifier formations are required for different fruits. Edible coating film formulation consisted on pectin, sorbitol, and bee wax was successfully used by Moalemiyan et al. to keep the fresh-cut mangoes in original state for over 2 weeks [92]. Whereas in a similar study, pectin coating containing sucrose and calcium lactate was able to prevent the fruits’ respiration rate and maintain sensory properties in fresh melon fruits for up to 14 days storage at 5°C. In a similar study [93], pectin edible coating solution containing pectin (3%), glycerol (2.5%), polyvinyl alcohol (1.25%), and citric acid (1%) was prepared and applied on sapota fruits by dipping method and uncoated sapota fruits were used as control. Both the treated and control fruits were stored at 30 ± 3°C. Physicochemical parameters namely, weight, color, firmness, acidity, TSS, pH, and ascorbic acid contents of both the coated and control fruits were measured at regular interval up to 11th day of the storage at 30 ± 3°C. Reduced rate of change in weight loss and other parameters were reported in pectin-coated sapota as compared to control fruits and it was observed that pectin film formulation was able to maintain good quality attributes and extend the shelf life of pectin-coated sapota fruits up to 11 days of storage at room temperature, whereas control fruits were edible up to 6 days. Furthermore, it was also observed that sapota fruits dipped in sodium alginate containing 2% pectin solution for 2 min were more effective in maintaining the organoleptic properties up to 30 days of refrigerated storage as compared to sapota fruits dipped for 4 min and untreated sapota fruits [94]. Bayarri et al. developed antimicrobial films using lysozyme and LM pectin complex. The main purpose of the study was to control the release of lysozyme in packaged food and to target lysozyme-sensitive bacteria such as Bacillus and Clostridium. It was observed that in the presence of fungal pectinase, due to the dissociation of pectin linkage, lysozyme activity of films increased remarkably. Many food-contaminating bacteria are pectinase producing and such type of films may be used to control food contaminants. These results have opened new avenues for custom-made biodegradable film [95].
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In last few years, some researchers have focused on pectin-based coating containing edible essential to improve the antimicrobial properties and to enhance the efficiency of the pectin films. Edible coating formulation containing sodium alginate and pectin (PE) enriched with eugenol (Eug) and citral (Cit) essential oil at different concentrations was used to increase the shelf life of strawberries. Physical and organoleptic parameters of coated fruits stored at 10°C for 14 days show that formulation containing PE 2% + Eug 0.1%; PE 2% + Cit 0.15% was more suitable than sodium alginate-based formulations [96]. Pectin coating containing lemon and orange peel essential oils was reported to increase the shelf life and quality attributes of the strawberry fruits up to 12 days when stored at 5°C. It was also observed that fruits coated with pectin + 1% orange essence showed less weight loss and soluble solids as compare to their control during the storage [97]. Sanchís et al. studied the combined effect of edible pectin coating with active modified atmospheric packaging on fresh-cut “Rojo Brillante” persimmon. Persimmon fruit slices were coated by dipping in the pectin-based emulsion or in water as control. Both the treated and control slices were packed under 5 kPa O2 (MAP) or under ambient atmosphere for up to 9 days at 5°C. Various parameters, such as package gas composition, color and firmness of slice, polyphenol oxidase activity, were measured during storage. It was observed that edible coating along with MAP significantly reduced the CO2 emission and O2 consumption in the packaged fruits. Furthermore, coating was also effective in controlling microbial growth and reducing enzymatic browning and maintains good sensory parameters up to 10 days on storage [98].
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Drying is the traditional and oldest method of fruit and vegetable preservation. It decreases the enzymatic activity, reduces the moisture contents, and protects the food from microbial attack. However, drying results in loss of nutrients, vitamins, heat-labile enzymes, modifies the texture, color, and organoleptic quality of dried fruits and vegetables and therefore diminishes the market value also. Pretreatment of food products with pectin coatings containing other bioactive compound such as ascorbic acid, CaCl2, edible gum, etc., before drying or blanching has been proposed as an effective method to preserve the nutritional as well as organoleptic quality of dried food [99]. Recent researches have shown that application of pectin coating could protect the moisture and vitamin C loss in pretreated papaya slice and osmotic dehydrated pineapple. In one of the research [100], pineapple slice was pretreated with pectin coating formulation containing (50%)/calcium lactate (4%)/ascorbic acid (2%) solutions and then dried by hot-air-drying method. Physicochemical analysis of dried product showed less reduction in vitamin C contents as compared to untreated pineapple slice. In a similar work, pectin coating supplement with vitamin C (1%) was used for precoating of papaya slice. It was found that incorporation of vitamin C did not affect the drying process. However, significant increase in vitamin C content was observed in final product [101].
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Frying is a method of cooking that causes changes in chemical and physical parameters of food and enhances the taste. However, high temperature vaporizes the water of food and affects the nutritional properties due to protein denaturation and starch gelatinization. The oil uptake during frying is affected by various parameters such as type of oil used, frying temperature and duration, product moisture content, shape, porosity, prefrying treatment, etc. [102]. Surface area and pretreatment of products are the major factors that determine the oil absorbed. Edible coating has also been used successfully, to reduce the oil uptake during frying in various deep-fried products. Reduction in oil uptake and improvement of texture and quality of potato slices was reported by Daraei Garmakhany et al. in 2008. Authors found that coating of potato slices with pectin, guar, and CMC solutions can reduce the oil uptake when compared with nontreated potato chips [103]. Similar results were also obtained by Khalil, where a combination of pectin or sodium alginate with calcium chlorides significantly reduces the oil uptake of French fries. Coating formulation of 0.5% calcium chloride and 5% pectin was most effective in reducing the oil uptake [104]. Kizito et al. used different edible coatings (pectin, carboxy methyl cellulose, agar, and chitosan) at a concentration of 1–2% for pretreatment of potato chips, followed by deep frying of chips. Fried chips were analyzed biochemically and organoleptically to investigate the quality attributes of the products. It was revealed that all the coating polymers were successful in reducing the oil uptake but pectin was most effective and reduced oil uptake up to 12.93%, followed by CMC (11.71%), chitosan (8.28%), and agar (5.25%) and significantly improved moisture retention of strips (p < 0.05) [105].
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6. Conclusion
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The application of natural polymers in food industry is increasing day by day. Researchers are focusing more and more toward the pectin because of the ease-of-availability, structural flexibility, and versatile composition. Pectin can be sourced from a number of easily available horticulture crops (Table 1). Pectin is a hydrocolloid which is used as a food emulsifier, gelling agent, thickener, and stabilizer. It is the preferred choice of most of the food processors as fat or sugar replacer in low-calorie foods. In the recent years, increasing demand of ready-to-serve foods, fresh-cut fruits, and vegetable has opened a new market for edible films. Being biodegradable and recyclable, a lot of research is being done on pectin-based edible film formulations. These films reduce the exchange of moisture, gases, lipids, and volatiles between food and environment, and also serve as protective barrier for microorganisms.
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Even though a lot of information is available regarding pectin structure and many pectin-based products are available in market, role of many carbohydrate moieties and their effect on various function of pectin are not yet well defined. Therefore, it is necessary to understand the structural-function relationship of pectin and its interactions for developing functional food products.
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Acknowledgments
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The authors thank Director, CSIR-CFTRI for the encouragement.
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Conflict of interest
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The authors declare no conflict of interest.
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\n',keywords:"pectin, pectin oligosaccharide, food emulsifier, edible films, functional food, food stabilizer, emulsified food",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/65793.pdf",chapterXML:"https://mts.intechopen.com/source/xml/65793.xml",downloadPdfUrl:"/chapter/pdf-download/65793",previewPdfUrl:"/chapter/pdf-preview/65793",totalDownloads:1784,totalViews:0,totalCrossrefCites:4,dateSubmitted:"October 31st 2018",dateReviewed:"December 20th 2018",datePrePublished:"February 22nd 2019",datePublished:null,dateFinished:null,readingETA:"0",abstract:"Pectin is a branched heteropolysaccharide consisting of long-chain galacturonan segments and other neutral sugars such as rhamnose, arabinose, galactose, and xylose. It forms a matrix with celluloses and hemicelluloses and contributes to the cell structure. Due to the presence of several sugar moieties and different levels of methyl esterification, pectin does not have defined molecular weight like other polysaccharides. Pectin has wide applications. It is used as emulsifier, gelling agent, thickener, stabilizer, and fat or sugar replacer in low-calorie foods. Pectin and pectin-derived oligosaccharides can also be used as an important ingredient in functional foods. In recent past, a new application envisaged for pectin polymers as edible films or coating. These films act as natural barrier for exchange of moisture, gases, lipids, and volatiles between food and environment, and protect fruits and vegetable from microbial contamination. The degree of esterification of pectin and other structural modifications defines the functional properties. Herein, various functional properties of pectin in relation to food processing and packaging are discussed.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/65793",risUrl:"/chapter/ris/65793",signatures:"Thiraviam Vanitha and Mahejibin Khan",book:{id:"8504",title:"Pectins",subtitle:"Extraction, Purification, Characterization and Applications",fullTitle:"Pectins - Extraction, Purification, Characterization and Applications",slug:"pectins-extraction-purification-characterization-and-applications",publishedDate:"January 22nd 2020",bookSignature:"Martin Masuelli",coverURL:"https://cdn.intechopen.com/books/images_new/8504.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"99994",title:"Dr.",name:"Martin",middleName:"Alberto",surname:"Masuelli",slug:"martin-masuelli",fullName:"Martin Masuelli"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Pectin structure",level:"1"},{id:"sec_3",title:"3. Pectin as food emulsifier",level:"1"},{id:"sec_3_2",title:"3.1 Mechanism of emulsion formation and stabilization",level:"2"},{id:"sec_4_2",title:"3.2 Pectin-containing emulsion-based food",level:"2"},{id:"sec_6",title:"4. Pectin as gelling agent",level:"1"},{id:"sec_7",title:"5. Pectin in food packaging",level:"1"},{id:"sec_8",title:"6. Conclusion",level:"1"},{id:"sec_9",title:"Acknowledgments",level:"1"},{id:"sec_9",title:"Conflict of interest",level:"1"}],chapterReferences:[{id:"B1",body:'Talbott LD, Ray PM. Molecular size and separability features of pea cell wall polysaccharides. Plant Physiology. 1992;92:357-368. DOI: 10.1104/pp.98.1.357'},{id:"B2",body:'Khan M, Ekambaram N, Umesh-Kumar S. Potential application of pectinase in developing functional foods. Annual Review of Food Science and Technology. 2013;4:21-34. DOI: 10.1146/annurev-food-030212-182525'},{id:"B3",body:'Monsoor MA, Proctor A. Preparation and functional properties of soy hull pectin. Journal of the American Oil Chemists\' Society. 2001;78(7):709-713. DOI: 10.1007/s11746-001-0330-z'},{id:"B4",body:'Kulkarni SG, Vijayanand P. Effect of extraction conditions on the quality characteristics of pectin from passion fruit peel (Passiflora edulis f. flavicarpa L.). LWT- Food Science and Technology. 2010;43:1026-1031. DOI: 10.1016/j.lwt.2009.11.006'},{id:"B5",body:'Levigne S, Ralet MC, Thibault JF. Characterization of pectins extracted from fresh sugar beet under different conditions using an experimental design. Carbohydrate Polymers. 2002;49:145-153. DOI: 10.1016/S0144-8617(01)00314-9'},{id:"B6",body:'Jiang YDY, Zhu X, Xiong H, Woo MW, Hu J. Physicochemical and comparative properties of pectins extracted from Akebia trifoliata var. australis peel. Carbohydrate Polymers. 2012;87:1663-1669. DOI: 10.1016/j.carbpol.2011.09.064'},{id:"B7",body:'Faravash RS, Ashtiani FZ. The influence of acid volume, ethanolto- extracts ratio and acid-washing time on the yield of pectic substances extraction from peach pomace. Food Hydrocolloids. 2008;22:196-202. DOI: 10.1016/j.foodhyd.2007.04.003'},{id:"B8",body:'HappiEmaga T, Ronkart SN, Robert C, Wathelet B, Paquot M. Characterisation of pectins extracted from banana peels (Musa AAA) under different conditions using an experimental design. Food Chemistry. 2008;108:463-471. DOI: 10.1016/j.foodchem.2007.10.078'},{id:"B9",body:'Urias-Orona V, Rascon-Chu A, Lizardi-Mendoza J, Carvajal-Millan E, Gardea A, Ramírez-Wong B. A novel pectin material: Extraction, characterization and gelling properties. International Journal of Molecular Sciences. 2010;11:3686-3695. DOI: 10.3390/ijms11103686'},{id:"B10",body:'Pagán J, Ibarz A, Llorca M, Pagán A, Barbosa-Cánovas GV. Extraction and characterization of pectin from stored peach pomace. Foodservice Research International. 2001;34:605-612. DOI: 10.1016/S0963-9969(01)00078-3'},{id:"B11",body:'Singthong J, Cui SW, Ningsanond S, Douglas Goff H. Structural characterization, degree of esterification and some gelling properties of Krueo Ma Noy (Cissampelos pareira) pectin. Carbohydrate Polymers. 2004;58:391-400. DOI: 10.1016/j.carbpol.2004.07.018'},{id:"B12",body:'Yapo BM. Pectin quantity, composition and physicochemical behaviour as influenced by the purification process. Food Research International. 2009;42:1197-1202. DOI: 10.1016/j.foodres. 2009.06.002'},{id:"B13",body:'Wai WW, Alkarkhi AFM, Azh Easa AM. Effect of extraction conditions on yield and degree of esterification of durian rind pectin: An experimental design. Food and Bioproducts Processing. 2010;88:209-214. DOI: 10.1016/j.fbp.2010.01.010'},{id:"B14",body:'Liu H, Xu XM, Guo SD. Comparison of full-fat and low-fat cheese analogues with or without pectin gel through microstructure, texture, rheology, thermal and sensory analysis. International Journal of Food Science and Technology. 2008;43:1581-1592. DOI: 10.1111/j.1365-2621.2007.01616.x'},{id:"B15",body:'Karnik D, Wicker L. Emulsion stability of sugar beet pectin fractions obtained by isopropanol fractionation. Food Hydrocolloids. 2017;74. DOI: 10.1016/j.foodhyd.2017.07.041'},{id:"B16",body:'Lim J, Yoo J, Ko S, Lee S. Extraction and characterization of pectin from Yuza (Citrus junos) pomace: A comparison of conventional-chemical and combined physical-enzymatic extractions. Food Hydrocolloids. 2012;29:160-165. DOI: 10.1016/j.foodhyd.2012.02.018'},{id:"B17",body:'Yapo BM, Koffi KL. Extraction and characterization of gelling and emulsifying pectin fractions from cacao pod husk. Journal of Food and Nutrition Research. 2013;1(4):46-51. DOI: 10.12691/jfnr-1-4-3'},{id:"B18",body:'Yapo BM, Koffi KL. Extraction and characterization of highly gelling low methoxy pectin from cashew apple pomace. Food. 2014;3(1):1-12. DOI: 10.3390/foods3010001'},{id:"B19",body:'Mackaman P, Tangsuphoom N, Chavasit V. Effect of extraction condition on the chemical and emulsifying properties of pectin from Cyclea barbata Miers leaves. International Food Research Journal. 2014;21(2):799-806'},{id:"B20",body:'Rahmati S, Abdullah A, Momeny E, Kang OL. Optimization studies on microwave assisted extraction of dragon fruit (Hylocereus polyrhizus) peel pectin using response surface methodology. International Food Research Journal. 2015;22(1):233-239'},{id:"B21",body:'Maskey B, Dhakal D, Pradhananga M, Shrestha NK. Extraction and process optimization of bael fruit pectin. Food Science & Nutrition. 2018;6:1927-1932. DOI: 10.1002/fsn3.761'},{id:"B22",body:'Xu SY, Liu JP, Huang X, Du LP, Shia FL, Dong R, et al. Ultrasonic-microwave assisted extraction, characterization and biological activity of pectin from jackfruit peel. LWT- Food Science and Technology. 2018;90:577-582. DOI: 10.1016/j.lwt.2018. 01.007'},{id:"B23",body:'Yang JS, Mu TH, Ma MM. Extraction, structure, and emulsifying properties of pectin from potato pulp. Food Chemistry. 2018;244:197-205. DOI: 10.1016/j.foodchem.2017.10.059'},{id:"B24",body:'Van Buggenhout S, Sila DN, Duvetter t VLA, Autio K, Hendrickx M. Pectins in processed fruits and vegetables: Part III—Texture engineering. Comprehensive Reviews in Food Science and Food Safety. 2009;8:105-117. DOI: 10.1111/j.1541-4337.2009.00072.x'},{id:"B25",body:'Huyskens-Keil S, Prono-Widayat H, Lüdders P, Schreiner M. Post-harvest quality of Pepino (Solanum muricatum ait.) fruit in controlled atmosphere storage. Journal of Food Engineering. 2006;77:628-634. DOI: 10.1016/j.jfoodeng.2005.07.028'},{id:"B26",body:'Van Linden V, Sila DN, Duvetter T, De Baerdemaeker J, Hendrickx M. Effect of mechanical impact-bruising on polygalacturonase and pectinmethylesterase activity and pectic cell wall components in tomato fruit. Postharvest Biology and Technology. 2008;47:98-106. DOI: 10.1016/j.postharvbio.2007.06.006'},{id:"B27",body:'ED Ngouémazong, Christiaens S, Shpigelman A, Van Loey AM, Hendrickx ME. The emulsifying and emulsion-stabilizing properties of pectin: A review. Comprehensive Reviews in Food Science and Food Safety. 2015;14:705e718. DOI: 10.1111/1541-4337.12160'},{id:"B28",body:'Thibault J, Renard C, Axelos M, Roger P, Crepeau M. Studies of the length of homogalacturonic regions in pectins by acid hydrolysis. Carbohydrate Research. 1993;238:271-286. DOI: 10.1016/0008-6215(93)87019-O'},{id:"B29",body:'Zhan D, Janssen P, Mort A. Scarcity or complete lack of single rhamnose residues interspersed within the homogalacturonan regions of citrus pectin. Carbohydrate Research. 1998;308:373-380. DOI: 10.1016/S0008-6215(98)00096-2'},{id:"B30",body:'Voragen AGJ, Coenen GJ, Verhoef RP, Schols HA. Pectin, a versatile polysaccharide present in plant cell walls. Structural Chemistry. 2009;20:263-275. DOI: 10.1007/s11224-009-9442-z'},{id:"B31",body:'Renard CM, Weightman RM, Thibault J. Xylose-rich pectins from pea hulls. International Journal of Biological Macromolecules. 1997;21:155-162. DOI: 10.1016/S0141-8130(97)00055-X'},{id:"B32",body:'Longland J, Fry SC, Trewavas A. Developmental control of apiogalacturonan biosynthesis and UDP-apiose production in duck weed. Plant Physiology. 1989;90:972-976. DOI: 10.1104/pp.90.3.972'},{id:"B33",body:'Komalavilas P, Mort AJ. The acetylation of O-3 of galacturonic acid in the rhamnose-rich portion of pectins. Carbohydrate Research. 1989;189:261-272. DOI: 10.1016/0008-6215(89)84102-3'},{id:"B34",body:'Vincken J, Schols H, Oomen R, McCann M, Ulvskov P, Voragen A, et al. If homogalacturonan were a side chain of rhamnogalacturonan I. implications of cell wall architecture. Plant Physiology. 2003;132:1781-1789. DOI: 10.1104/pp.103.022350'},{id:"B35",body:'Ridley BL, O’Neil MA, Mohnen D. Pectins: Structure, biosynthesis and oligogalacturonide-related signalling. Phytochemistry. 2001;57:929-967. DOI: 10.1016/S0031-9422(01)00113-3'},{id:"B36",body:'O’Neill MA, York WS. The composition and structure of plant primary cell walls. In: Rose JKC, editor. The Plant Cell Wall. Boca Raton, Fla.: Blackwell/CRC; 2003. pp. 1-54. DOI: 10.1093/aob/mch185'},{id:"B37",body:'Yapo BM. Rhamnogalacturonan-I: A structurally puzzling and functionally versatile polysaccharide from plant cell walls and mucilages. Polymer Reviews. 2011;51:391-413. DOI: 10.1080/15583724.2011.615 962'},{id:"B38",body:'Coenen GJ, Bakx EJ, Verhoef RP, Schols HA, Voragen AGJ. Identification of the connecting linkage between homo- or xylogalacturonan and rhamnogalacturonan type I. Carbohydrate Polymers. 2007;70:224-235. DOI: 10.1016/j.carbpol.2007.04.007'},{id:"B39",body:'Seymour GB, Knox JP. Pectins and their Manipulation. Oxford: Blackwell Publishing Ltd; 2002'},{id:"B40",body:'Yapo BM. Pectic substances: From simple pectic polysaccharides to complex pectins—A new hypothetical model. Carbohydrate Polymers. 2011b;86:373-385. DOI: 10.1016/j.carbpol.2011.05.065'},{id:"B41",body:'Alistair MS, Glyn OP, Peter AW. Food Polysaccharides and their Applications. Florida: CRC Press; 2014. pp. 357-364'},{id:"B42",body:'Funami T, Zhang G, Hiroe M, Noda S, Nakauma M, Asai I, et al. Effects of the proteinaceous moiety on the emulsifying properties of sugar beet pectin. Food Hydrocolloids. 2007;21:1319-1329. DOI: 10.1016/j.foodhyd.2006.10.009'},{id:"B43",body:'Gullon B. Gómez B, Martínez-Sabajanes M, Yáñez R, Parajó JC, Alonso JL. Pectic oligosaccharides: manufacture and functional properties. Trends in Food Science and Technology. 2013;30:153-161. DOI: 10.1016/j.tifs.2013.01.006'},{id:"B44",body:'Mohnen D. Pectin structure and biosynthesis. Current Opinion in Plant Biology. 2008;11:266-277. DOI: 10.1016/j.pbi.2008.03.006'},{id:"B45",body:'de Vries JA, Hansen M, Soderberg J, Glahn PE, Pederson JK. Distribution of methoxyl groups in pectins. Carbohydrate Polymers. 1986;6:165. DOI: 10.1016/0144-8617(86)90017-2'},{id:"B46",body:'Leroux J, Langendorff V, Schick G, Vaishnav V, Mazoyer J. Emulsion stabilizing properties of pectin. Food Hydrocolloids. 2003;17:455-462. DOI: 10.1016/S0268-005X(03)00027-4'},{id:"B47",body:'Willats WGT, McCartney L, Mackie W, Knox JP. Pectin: Cell biology and prospects for functional analysis. Plant Molecular Biology. 2001;47:9-27. DOI: 10.1023/A:101066291'},{id:"B48",body:'ED Ngouémazong, Jolie RP, Cardinaels R, Fraeye I, VanLoey A, Moldenaers P, et al. Stiffness of Ca2+pectin gels: Combined effects of degree and pattern of methyl esterification for various Ca2+ concentrations. Carbohydrate Research. 2012;348:69-76. DOI: 10.1016/j.carres.2011.11.011'},{id:"B49",body:'Georget D, Ng A, Smith A, Waldron K. The thermo mechanical properties of carrot cell wall material. Journal of the Science of Food and Agriculture. 1998;78:73-80. DOI: 10.1016/S0040-6031(98)00276-7'},{id:"B50",body:'Sila DN, Doungla E, Smout C, Van Loey A, Hendrickx M. Pectin fractions inter conversions: Insight into understanding texture evolution of thermally processed carrot. Journal of Agricultural and Food Chemistry. 2006;54(22):8471-8479. DOI: 10.1021/jf0613379'},{id:"B51",body:'Frank K, Köhler K, Schuchmann HP. Formulation of labile hydrophilic ingredients in multiple emulsions: Influence of the formulation’s composition on the emulsion’s stability and on the stability of entrapped bioactives. Journal of Dispersion Science and Technology. 2011;32:1753-1758. DOI: 10.1080/01932691 .2011.616147'},{id:"B52",body:'Mcclements DJ, Decker EA, Weiss J. Emulsion-based delivery systems for lipophilic bioactive components. Journal of Food Science. 2007;72:R109-R124. DOI: 10.1111/j.1750-3841.2007.00507.x'},{id:"B53",body:'Nakamura A, Takahash T, Yoshida R, Maeda H, Corredig M. Emulsifying properties of soybean soluble polysaccharide. Food Hydrocolloids. 2004;18:795-803. DOI: 10.1016/j.foodhyd.2003.12.005'},{id:"B54",body:'Surh J, Decker E, McClements D. Influence of pH and pectin type on properties and stability of sodium-caseinate stabilized oil-in-water emulsions. Food Hydrocolloids. 2006;20:607-618. DOI: 10.1016/j.foodhyd.2005.07.004'},{id:"B55",body:'Chassaing K, Koren O, Goodrich JK, Poole AC, Srinivasan S, Ley RE, et al. Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome. Nature. 2015, 2015;519(7541):92-96. DOI: 10.1038/nature14232'},{id:"B56",body:'Viennois E, Merlin D, Gewirtz A, Chassaing B. Dietary emulsifier-induced low-grade inflammation promotes colon carcinogenesis. Cancer Research. 2017;77(1):27-40. DOI: 10.1158/0008-5472.CAN-16-1359'},{id:"B57",body:'Dickinson E. Hydrocolloids at interfaces and the influence on the properties of dispersed systems. Food Hydrocolloids. 2003;17:25-39. DOI: 10.1016/S0268-005X(01)00120-5'},{id:"B58",body:'Thakur BR, Singh RK, Handa AK. Chemistry and uses of pectin - a review. Critical Reviews in Food Science and Nutrition. 1997;37:47-73. DOI: 10.1080/10408399709527767'},{id:"B59",body:'Akhtar K, Dickinson E, Mazoyer J, Langendorff V. Emulsion stabilizing properties of depolymerized pectin. Food Hydrocolloids. 2002;16:249-256. DOI: 10.1016/S0268-005X(01)00095-9'},{id:"B60",body:'Dickinson E. Hydrocolloids as emulsifiers and emulsion stabilizers. Food Hydrocolloids. 2009;23:1473-1482. DOI: 10.1016/j.foodhyd.2008.08.005'},{id:"B61",body:'Jung J, Wicker L. Laccase-mediated conjugation of sugar beet pectin and the effect on emulsion stability. Food Hydrocolloids. 2012;28:168-173. DOI: 10.1016/j.foodhyd.2011.12.021'},{id:"B62",body:'Siew CK, Williams PA, Cui SW, Wang Q. Characterization of the surface-active components of sugar beet pectin and the hydrodynamic thickness of the adsorbed pectin layer. Journal of Agricultural and Food Chemistry. 2008;56:8111-8120. DOI: 10.1021/jf801588a'},{id:"B63",body:'Funami T, Nakauma M, Ishihara S, Tanaka R, Inoue T, Phillips GO. Structural modifications of sugar beet pectin and the relationship of structure to functionality. Food Hydrocolloids. 2011;25:221-229. DOI: 10.1016/j.foodhyd.2009.11.017'},{id:"B64",body:'McClements DJ. Protein-stabilized emulsions. Current Opinion in Colloid & Interface Science. 2004;9:305-313. DOI: 10.1016/j.cocis.2004.09.003'},{id:"B65",body:'Yoo S-H, Fishman ML, Hotchkiss AT Jr, Lee HG. Viscometric behavior of high-methoxy and low-methoxy pectin solutions. Food Hydrocolloids. 2006;20:62-67. DOI: 10.1016/ j.foodhyd. 2005.03.003'},{id:"B66",body:'Lutz R, Aserin A, Wicker L, Garti N. Structure and physical properties of pectins with block-wise distribution of carboxylic acid groups. Food Hydrocolloids. 2009;23:786-794. DOI: 10.1016/j.foodhyd.2008.04.009'},{id:"B67",body:'Williams PA, Sayers C, Viebke C, Senan C, Mazoyer J, Boulenguer P. Elucidation of the emulsification properties of sugar beet pectin. Journal of Agricultural and Food Chemistry. 2005;53:3592-3597. DOI: 10.1021/jf0404142'},{id:"B68",body:'Castellani O, Al-Assaf S, Axelos M, Phillips GO, Anton M. Hydrocolloids with emulsifying capacity. Part 2- adsorption properties at the n-hexadecane-water interface. Food Hydrocolloids. 2010;24:121-130. DOI: 10.1016/j.foodhyd.2009.07.006'},{id:"B69",body:'Nakai S. Structure-function relationships of food proteins with an emphasis on the importance of protein hydrophobicity. Journal of Agricultural and Food Chemistry. 1983;31:676-683. DOI: 10.1021/jf00118a001'},{id:"B70",body:'Lobato-Calleros C, Recillas-Mota MT, Espinosa-Solares T, Alvarez-Ramirez J, Vernon-Carter EJ. Microstructural and rheological properties of low-fat stirred yoghurts made with skim milk and multiple emulsions. Journal of Texture Studies. 2009;40:657-675. DOI: 10.1111/j.1745-4603.2009.00204.x'},{id:"B71",body:'Liu H, Xu XM, Guo SD. Comparison of full-fat and low-fat cheese analogues with or without pectin gel through microstructure, texture, rheology, thermal and sensory analysis. International Journal of Food Science and Technology. 2008;43:1581-1592. DOI: 10.1111/j.1365-2621.2007.01616.x'},{id:"B72",body:'Lobato-Calleros C, Sosa-Pérez A, Rodríguez-Tafoya J, Sandoval-Castilla O, Pérez-Alonso C, Vernon-Carter EJ. Structural and textural characteristics of reduced-fat cheese-like products made from W1/O/W2 emulsions and skim milk. LWT- Food Science and Technology. 2008;41:1847-1856. DOI: 10.1016/j.lwt.2008.01.006'},{id:"B73",body:'Pedersen A, Christian H: No and low fat mayonnaise compositions. United States of American Patent No. 5641533; 1997'},{id:"B74",body:'Endress H-U, Mattes F, Norz K. Pectins. In: Hui YH, editor. Handbook of Science, Technology and Engineering. London: CRC Taylor & Francis; 2006. pp. 1401-1435'},{id:"B75",body:'Liu H, Xu XM, Guo SD. Rheological, texture and sensory properties of low-fat mayonnaise with different fat mimetics. Food Science and Technology. 2007;40:946-954. DOI: 10.1016/j.lwt.2006.11.007'},{id:"B76",body:'Yashodhara BM, Umakanth S, Pappachan JM, Bhat SK, Kamath R, Choo BH. Omega-3 fatty acids: A comprehensive review of their role in health and disease. Postgraduate Medical Journal. 2009;85:84-90. DOI: 10.1136/pgmj.2008.073338'},{id:"B77",body:'Méndez-Zamora G, García-Macías JA, Santellano-Estrada E, Chávez Martínez A, Durán-Meléndez LA, Silva-Vázquez R, et al. Fat reduction in the formulation of frankfurter sausages using inulin and pectin. Food Science and Technology (Campinas). 2015;35:25-31. DOI: 10.1590/1678-457X.6417'},{id:"B78",body:'Silva-Vazquez R, Flores-Giron E, Quintero-Ramos A, Hume ME, Mendez-Zamora G. Effect of inulin and pectin on physicochemical characteristics and emulsion stability of meat batters. Cyta – Journal of Food. 2018;16:306-310. DOI: 10.1080/19476337.2017.1403490'},{id:"B79",body:'Löfgren C, Guillotin S, Evenbratt H, Schols HA, Hermansson AM. Effects of calcium, pH, and blockiness on kinetic rheological behavior and microstructure of HM pectin gels. Biomacromolecules. 2005;6(2):646-652. DOI: 10.1021/bm049619+'},{id:"B80",body:'Williams PA. Renewable Resources for Functional Polymers and Biomaterials: Polysaccharides, Proteins and Polyesters. Cambridge, UK: Royal Society of Chemistry; 2011. DOI: 10.1039/9781849733519'},{id:"B81",body:'McClements DJ. Food Emulsions: Principles, Practice, and Techniques. Boca Raton, USA: CRC Press; 2016. https://doi.org/10.1201/b18868'},{id:"B82",body:'Neirynck N, Van der Meeren P, Gorbe BS, Dierckx S, Dewettinck K. Improved emulsion stabilizing properties of whey protein isolate by conjugation with pectins. Food Hydrocolloids. 2004;18:949-957. DOI: 10.1016/j.foodhyd.2004.03.004'},{id:"B83",body:'Kjøniksen AL, Hiorth M, Nyström B. Association under shear flow in aqueous solutions of pectin. European Polymer Journal. 2005;41:761. DOI: 10.1016/j.eurpolymj.2004.11.006'},{id:"B84",body:'Kuuva T, Lantto R, Reinikainen T, Buchert J, Autio K. Rheological properties of laccase-induced sugar beet pectin gels. Food Hydrocolloids. 2003;17:679-684. DOI: 10.1016 /S0268-005X(03)00034-1'},{id:"B85",body:'Acosta O. Víquez F, Cubero E: Optimisation of low-calorie mixed fruit jelly by response surface methodology. Food Quality and Preference. 2008;19(1):79-85. DOI: 10.1016/j.foodqual.2007.06.010'},{id:"B86",body:'Valdés A, Burgos N, Jiménez A, Garrigós MC. Natural pectin polysaccharides as edible coatings. Coatings. 2015;5(4):865-886. DOI: 10.3390/coatings5040865'},{id:"B87",body:'Bourtoom T. Edible films and coatings: Characteristics and properties. International Food Research Journal. 2008;15:237-248'},{id:"B88",body:'Ciolacu L, Nicolau AI, Hoorfar J. Global Safety of Fresh Produce. A Handbook of Best Practice, Innovative Commercial Solutions and Case Studies. Sawston, UK: Woodhead Publishing Limited; 2014'},{id:"B89",body:'Zhang Y, Rempel C, McLaren D. Edible coating and film materials: Carbohydrates. In: Innovations in Food Packaging. 2nd ed. Amsterdam, The Netherlands: Elsevier; 2014. pp. 305-323. DOI: 10.1016/B978-0-12-394601-0.00012-6'},{id:"B90",body:'Maftoonazad N, Ramaswamy HS. Effect of pectin-based coating on the kinetics of quality change associated with stored avocados. Journal of Food Processing & Preservation. 2008;32:621-643. DOI: 10.1111/j.1745-4549.2008.00203.x'},{id:"B91",body:'Oms-Oliu G, Soliva-Fortuny R, Martín-Belloso O. Using polysaccharide-based edible coatings to enhance quality and antioxidant properties of fresh-cut melon. LWT - Food Science and Technology. 2008;41:1862-1870. DOI: 10.1016/j.lwt.2008.01.007'},{id:"B92",body:'Moalemiyan M, Ramaswamy HS, Maftoonazad N. Pectin-based edible coating for shelf-life extension of ataulfo mango. Journal of Food Process Engineering. 2012;35:572-600. DOI: 10.1111/j.1745-4530.2010.00609.x'},{id:"B93",body:'Menezes J, Athmaselvi KA. Polysaccharide based edible coating on sapota fruit. International Agrophysics. 2016;30:551-557. DOI: 10.1515/intag-2016-0019'},{id:"B94",body:'Menezes J, Athmaselvi KA. Study on effect of pectin based edible coating on the shelf life of sapota fruits. Biosciences, Biotechnology Research Asia. 2016;13(2). DOI: 10.13005/bbra/2152'},{id:"B95",body:'Bayarri M, Oulahal N, Degraeve P, Gharsallaoui A. Properties of lysozyme/low methoxyl (LM) pectin complexes for antimicrobial edible food packaging. Journal of Food Engineering. 2014;131:18-25. DOI: 10.1016/j.jfoodeng.2014.01.013'},{id:"B96",body:'Guerreiro AC, Gago CML, Faleiro ML, Miguel MGC, Antunes MDC. The use of polysaccharide-based edible coatings enriched with essential oils to improve shelf-life of strawberries. Postharvest Biology and Technology. 2015;110:51-60. DOI: 10.1016/j.postharvbio.2015.06.019'},{id:"B97",body:'Abdi S, Roein Z, Erfanimoghadam J, Aziznia S. Application of pectin coating containing essential oil for increasing quality of strawberry fruit. Journal of Postharvest Technology. 2017;5(4):83-94'},{id:"B98",body:'Sanchís E, Ghidelli C, Sheth CC, Mateos M, Palou L, Pérez-Gago MB. Integration of antimicrobial pectin-based edible coating and active modified atmosphere packaging to preserve the quality and microbial safety of fresh-cut persimmon (Diospyros kaki Thunb. cv. Rojo Brillante). Journal of the Science of Food and Agriculture. 2017;97(1):252-260. DOI: 10.1002/jsfa.7722'},{id:"B99",body:'Oliveira SM, Brandão TRS, Silva CLM. Influence of drying processes and pretreatments on nutritional and bioactive characteristics of dried vegetables: A review. Food Engineering Reviews. 2015;8:134163. DOI: 10.1007/s1239 3-015-9124-0'},{id:"B100",body:'Silva KS, Garcia CC, Amado LR, Mauro MA. Effects of edible coatings on convective drying and characteristics of the dried pineapple. Food and Bioprocess Technology. 2015;8:1465-1475. DOI: 10.1007/s11947-015-1495-y'},{id:"B101",body:'Canizares D, Mauro MA. Enhancement of quality and stability of dried papaya by pectin-based coatings as air-drying pretreatment. Food and Bioprocess Technology. 2015;8:1187-1197'},{id:"B102",body:'Pinthus EJ, Saguy IS. Initial interfacial tension and oil uptake by deep-fat fried foods. Journal of Food Science. 1994;59:804, 823-807. DOI: 10.1111/j.1365-2621.1994.tb08132.x'},{id:"B103",body:'Daraei Garmakhany A, Mirzaei HO, Kashani Nejad M, Maghsudlo Y. Study of oil uptake and some quality attributes of potato chips affected by hydrocolloids. European Journal of Lipid Science and Technology. 2008;110:1045-1049. DOI: 10.1002/ejlt.200700255'},{id:"B104",body:'Khalil AH. Quality of french fried potatoes as influenced by coating with hydrocolloids. Food Chemistry. 1999;66:201-206. DOI: 10.1016/S0308-8146(99)00045-X'},{id:"B105",body:'Kizito KF, Abdel-Aal MH, Ragab MH, Youssef MM. Quality attributes of French fries as affected by different coatings, frozen storage and frying conditions. Journal of Agricultural Science and Botany. 2017;1(1):23-29'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Thiraviam Vanitha",address:null,affiliation:'
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