\r\n\t• Role of technological innovation and corporate risk management \r\n\t• Challenges for corporate governance while launching corporate environmental management among emerging economies \r\n\t• Demonstrating the relationship between environmental risk management and sustainable management \r\n\t• Contemplating strategic corporate environmental responsibility under the influence of cultural barriers \r\n\t• Risk management in different countries – the international management dimension \r\n\t• Global Standardization vs local adaptation of corporate environmental risk management in multinational corporations. \r\n\t• Is there a transnational approach to environmental risk management? \r\n\t• Approaches towards Risk management strategies in the short-term and long-term.
",isbn:"978-1-83968-906-2",printIsbn:"978-1-83968-905-5",pdfIsbn:"978-1-83968-907-9",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,hash:"9b65afaff43ec930bc6ee52c4aa1f78f",bookSignature:"Dr. Muddassar Sarfraz and Prof. Larisa Ivascu",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/10226.jpg",keywords:"Global Risk Management, Risk Assessment, Climate Risk, Environmental Management, International Business, Business Sustainability, Corporate Governance, Financial Market, Financial Risks, Sustainable Economic Environment, Business Valuation, Organizational Behavior",numberOfDownloads:102,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"September 24th 2020",dateEndSecondStepPublish:"October 22nd 2020",dateEndThirdStepPublish:"December 21st 2020",dateEndFourthStepPublish:"March 11th 2021",dateEndFifthStepPublish:"May 10th 2021",remainingDaysToSecondStep:"4 months",secondStepPassed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"Dr. Muddassar Sarfraz focuses on corporate social responsibility, human resource management, strategic management, and business management. 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He is an Editorial Board Member of the International Journal of Human Resource as well as a member of the British Academy of Management (UK), Chinese Economists Society (USA), World Economic Association (UK), American Economic Association (USA), and an Ambassador of the International MBA program of Chongqing University, PR China, for Pakistan. \nHis research focuses on corporate social responsibility, human resource management, strategic management, and business management.",institutionString:"Binjiang College, Nanjing University of Information Science &Technology, Wuxi, Jiangsu",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"1",institution:null}],coeditorOne:{id:"288698",title:"Prof.",name:"Larisa",middleName:null,surname:"Ivascu",slug:"larisa-ivascu",fullName:"Larisa Ivascu",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRfMOQA0/Profile_Picture_1594716735521",biography:"Dr Larisa IVAȘCU is currently an associate professor at the Politehnica University of Timisoara. 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1. Introduction
Neurodegeneration refers to a progressive structural and functional loss of neurons causing heterogeneous clinical and pathological expressions followed by deterioration of functional anatomy [1]. This progressive neuronal cell death often leads to various neurodegenerative disorders (NDDs) such as Parkinson’s disease (PD), Huntington’s disease (HD), Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), brain trauma (BT), prion disease (PrD), progressive supranuclear palsy (PSP), and spinocerebellar ataxias (SCA), etc., which can be differentiated based on their different pathological mechanistic pathways. It includes associated neuropathology, disease based anatomical vulnerability, and aggregation of some major selective proteins during disease conditions [2]. In the last few decades, several approaches have been taken to understand the mechanisms of neuronal cell death [3]. The oxidative and nitrosative stress due to the overproduction of reactive oxygen species (ROS) and reactive nitrogen species (RNS) with the deterioration of cellular antioxidant defense systems are found to be the major reasons behind this neuronal cell damage which might further lead to NDDs [4]. In this context, it is obvious to mention that the oxidoreductase enzymes which are responsible to increase the oxidant level in the cellular microenvironment are one of the major culprits of these sophisticated diseases [4, 5, 6]. These pathways and mechanisms of these biochemical processes leading towards the cell deaths are found to be different for various neurodegenerative diseases as observed by their symptoms and exacerbations [4, 5, 6]. The common neuropathological hallmarks of such diseases are (a) stress-induced generation of free radicals (b) abnormal protein dynamics, their degradation, and aggregation (c) mitochondrial dysfunctions and (d) neuroinflammation [2] (Figure 1). Advanced immunohistochemical and biochemical methods are now able to identify the specific protein abnormalities, related to each of the classes of NDDs [7]. These proteins mostly follow the brain region-specific sequential distribution patterns, suggesting a cell-to-cell propagation [7, 8]. Recently, it is also found that some of the neurodegeneration associated proteins can be detected in peripheral organs and may also present concomitantly in the brain and peripheral tissues [9]. These identified molecular pathological backgrounds of the disease-associated proteins along with the inconsistent clinical symptoms of NDDs create a necessity of proper neuropathological examinations like developments of biomarkers, clinical and neuroimaging studies which finally lead to the accurate diagnosis [9]. The treatment of these neurodegenerative diseases are mostly symptomatic such as dopaminergic treatment for PD and movement disorders, anti-inflammatory and analgesic for neuronal infections and pain, cholinesterase for cognitive disorders, antipsychotic for dementia, etc. though, further progress in therapeutic management is needed to treat many other progressive and serious symptoms of the diseases [10, 11, 12]. Integrative treatments along with medicinal therapies are also in the frontline of research to improve the endogenous antioxidant systems targeting the oxidoreductase enzymes and thereby the activity of daily life of the neurodegenerative patients. These integrated treatments act by protecting against oxidative and nitrosative stress related neuropsychiatric disorders, sensory and other symptoms of non-motor fluctuations, fatigue, etc. [11]. In this chapter, the diagnostic classification of NDDs, their preventive strategy, and treatment with a special emphasis on the oxidoreductase enzymes are summarized to understand the current progress in the field of NDDs.
Figure 1.
Schematic presentation of possible steps for the action of different factors involve in the development of neurodegeneration.
2. Role of oxidative stress in neurodegenerations
While aging is the key contributor to most of the NDDs, oxidative stress is the main factor for functional impairment during aging due to the oxidation of lipids, deoxyribonucleic acid (DNA), and proteins in presence of reactive oxygen or nitrogen species (ROS or RNS). Thus, it is not unreasonable to assume that enhancement in level(s) of ROS and/or RNS increase(s) the senescence of cells by secreting pro-inflammatory factors and enzymes followed by cellular degradation [13] (Figure 1). S-Nitrosylation reaction plays a crucial role in nitric oxide (NO) bioactivity and is shown to have neuroprotective as well as a neurotoxic role based on the targeted protein [14]. An increase in level of nitrosative stress may affect mitochondrial respiration by inhibiting its complexes I and IV and disrupts the mitochondrial dynamics followed by synaptic injury and neuronal damage [15]. Thus, it may be corroborated that this RNS mediated protein modification is associated with AD pathology, as AD can be characterized by increasing mitochondrial dysfunction [16, 17]. On the other hand, an increase in the level of amyloid-beta (Aβ) and aging aggravate the senescent phenotype and endothelial cell dysfunction and can be characterized by oxidative stress [13]. It is well proved that reduction in oxidative stress can reduce the cognitive impairment and inflammatory processes as oxidative stress enhances the loss of homeostasis [6]. Increased level of oxidative stress also enhances the production of the inflammatory cytokine and finally both affect the cognitive performance in aged individuals [4]. In this context, it is obvious to mention that the involvement of oxidoreductases in oxidative stress is a well-accepted logic-based fact in NDDs [18, 19].
2.1 Role of oxidoreductase in NDDs
Oxidoreductases are the enzymes that catalyze the oxidation–reduction reactions by transferring electrons from oxidant to reductant. It can be classified as oxidases, dehydrogenases, peroxidases, hydroxylases, oxygenases, and reductases. It has been found that increased levels of oxidative stress biomarker glutathione peroxidase (GSH-Px) and reduction in its (GSH-Px) activity are associated with an increase in inflammatory cytokines and both of them has a correlation with the cognitive impairment of elderly individuals [4]. Increased expression of nuclear factor erythroid2-related factor 2 (Nrf2) and reduced level of superoxide dismutase 1 mRNA are associated with cognitive impairments [20]. Nrf2 is the main controller of oxidative response and toxic insults to cells and modulate the expression of the inflammatory, metabolism-related gene [21]. Signaling pathways such as glycogen synthase kinase 3 (GSK-3), nuclear factor kappa light chain enhancer of activated B cells (NF-κB), NOTCH, and adenosine monophosphate kinase (AMP kinase) and Kelch ECH associating protein 1 (Keap1) regulates the Nrf2 activity [6, 22]. It has been observed that Nrf2 deficiency along with amyloidopathy and tauopathy induce neuroinflammation and oxidative stress providing a direct connection between neurodegeneration and oxidoreductase system [23]. Harada et al. [18] have shown a positive association of the NQO2 (dihydronicotonamide riboside (NRH): quinone oxidoreductase 2, or QR2) and PD as the deletion of 29-bp nucleotides in the promoter region of the NQO2 gene associates with the development of PD. In presence of catechol quinones, the over-expression of NQO2 in brain cells leads to the production of ROS (via the rapid conversion of superoxide radicals into hydrogen peroxide and then into highly reactive hydroxyl radicals)-induced neuronal cell death or neurodegeneration [5]. The other isoform of NAD(P)H:quinone acceptor oxidoreductase (NQO), the NQO1, or NADH quinone oxidoreductase of mitochondria carries the most common Leber’s hereditary optic neuropathy (LHON) mutants [24]. The protein disulfide isomerase (PDI) enzyme is another potent oxidoreductase resides in the endoplasmic reticulum, has the ability to catalyze the oxidative folding reactions requires for the maturation of disulfide-bond-containing proteins. It is found to regulate the molecular trafficking along the secretory pathway to prevent the protein misfolding which can mitigate the proteinopathy-induced neurodegenerative diseases (e.g., AD, PD). Monoamine oxidase (MAO) is another oxidoreductase which is predominantly found in the brain regional and platelet mitochondrial outer membrane catalyzes the amine (-NH2) compound (monoamine neurotransmitters e.g., serotonin (5-HT), dopamine) and formaldehyde and hydrogen peroxide (H2O2) as byproducts. During aging the MAO-A activity has been found to be increased in cerebral cortex, hippocampus, hypothalamus, and pons-medulla [25, 26] whereas, decrease in blood platelets [27]. Very limited information are available there about the aldo-keto oxidoreductase (aldehyde dehydrogenase or ALDH, aldose reductase, aldehyde reductase, alcohol dehydrogenase) which can detoxify the reactive aldehyde and ketone bodies in the brain bearing a protective role from the development of aging-induced neurodegenerative diseases, especially AD. The oxidative damage to the polyunsaturated fatty acids (PUFA) generates the 4-hydroxy-trans-2- nonenal (HNE) and its related carbonyl, which creates immunoreactivity. Their elevated levels are found in the brain as well as in cerebrospinal fluid (CSF) of AD, PD, and ALS patients [28]. It (reactive aldehydes) inhibits mitochondrial functions, disrupts cytoskeleton, inhibits glutamate transporters, and also modifies tubulin structure [29, 30]. The aldo-keto oxidoreductases have the ability to detoxify these reactive aldehydes in brain by converting those into corresponding acid or alcohol [31, 32]. The ALDH has been found in the cerebral cortex, hippocampus, basal ganglia, and midbrain, and aldose reductase in the pyramidal cells of cerebral cortex and hippocampal CA1 region, while all of these oxidoreductases are present in cerebellum [19] providing and strengthening the evidence of the fact that cerebellum is less vulnerable in the proteinopathy related NDDs. The xanthine oxidoreductase which converts hypoxanthine to xanthine and thereby to uric acid-producing H2O2 as a byproduct can generate superoxide via NADH oxidase activity and similar to ALDH, manganese superoxide dismutase (Mn-SOD) and heme-oxygenase-1 (HO-1) are promptly expressed in reactive astrocytes and found to be present in healthy pyramidal neurons [33, 34].
3. Types of neurodegeneration
NDDs often overlap with each other based on pathology and symptoms especially in multisystem atrophy where several areas get affected at a time making it difficult to analyze clinically [35]. Based on the predominant pathological features and topography of the central nervous system (CNS) during the diseased condition, NDDs have been classified into three major aspects:
3.1 Anatomical classification
The anatomical positions (such as cerebral cortex, basal ganglia, brainstem, cerebellum, spinal cord) in relation to the disease condition (Table 1) can be used as a component to identify the disease and also for its classification [7]. For example, dementia is a pathological condition due to neurodegeneration in the cerebral cortex as observed in AD patients. Similarly abnormal motor functions as observed in PD are associated with degenerations involving basal ganglia including nucleus putamen, globus pallidus, substantia nigra, subthalamic nucleus, red nucleus, and some thalamic and brainstem nuclei, etc. (Table 1) [7].
Disease
Main anatomic vulnerability
Symptoms
Main neuropathology
Protein aggregate(s)
Diagnostic approaches
Therapeutic strategies
References
Alzheimer’s disease
Basal forebrain, Frontal and Temporal lobes, Limbic structures, Locus coeruleus and Olfactory bulb
Cognitive and functional impairment, Dementia like memory loss, Problems with abstract thinking, Planning, Flexibility, Motor tasks, Neuropsychiatric manifestations and Language problem
Neurofibrillary tangles (NFTs), Neuropil threads, Neuritic and amyloid plaques and Amyloid angiopathy
Aβ 3R+ 4R tau
Anatomical distribution of (a) neuronal tau pathology, (b)extracellular Aβ deposits and (c) CAA
iAβ5 (Chaperon) for inhibiting protein aggregates, Donepezil and Rivastigmine drug therapy, APP regulation by latrepirdine and treatment with cholinesterase inhibitors and HDACi
Finkel, 2004 [36]; Desai and Grossberg; 2005 [10]; Okun et al., 2004 [37]
Parkinson’s disease
Substantia nigra pars compacta, Trans-entorhinal region, Motor and Sensory cortex, Prefrontal cortex, Dorsal motor nuclei of the medulla oblongata, Raphe nucleus and Locus coeruleus of the brainstem
Motor symptoms: Tremor (resting), Muscle rigidity, Postural instability, Coordination problem, Slow movements, Bradykinesia and Loss of physical movement, Non motor symptoms: High-level cognitive dysfunction, Psychiatric and emotional changes, Depression, Difficulty in swallowing and speaking, Sensory symptoms and Constipation and/or Urinary problems
Neuronal degeneration of dopaminergic neurons
α-synuclein
Estimation of the activity of terminal dopa decarboxylase (DDC), Evaluation of the availability of presynaptic dopamine transporters (DAT) and Vesicular monoamine transporter 2 (VMAT2) density measurements in dopamine terminals.
Combination of Levodopa and Carbidopa, Inducers of Hsp104 chaperones, Targeting of α- synuclein misfolding with Hsp 70, Treatments with anti-inflammatory drugs against Methyl-4-phenylpyridinium induced autophagy and Knockdown of Sirt2 by siRNA
Dementia, Difficulties in walking and speaking, Fatigue, Muscle stiffness, Hallucination and Confusion
Spongiform changes and Prion protein (PrP) accumulation
PrP
Morphology of PrP deposition, Glycosylation pattern and electrophoretic mobility of PK-resistant PrP by using western blot technique, Codon 129 polymorphism and Aetiology if known
RNAi-mediated silencing of host-encoded cellular prion protein (PrPC)
Superior medial frontal cortex, Superior dorsolateral frontal cortex, Medial occipital lobe, Lateral occipital cortex, Deep inferior parietal white matter, and Pons
Depression, Fatigue, Anxiety, Personality change, Tremor, Unilateral loss of vision, Pain, Bladder problems, Constipation and Impaired hearing
Inflammation and Demyelination
TDP-43, SOD1, FUS and DPRs
Morphological, subcellular and anatomical distribution of protein deposits
Immunomodulation by beta-interferon, Ocrelizumab etc and Hormonal replacement therapy
3.2 Based on conformational and biochemical modifications of proteins
Some proteins and their cellular aggregation as identified, are associated with NDDs and found to undergo conformational and biochemical modifications during disease pathology [7]. Proteins such as microtubule-associated protein Tau encoded by MAPT on 17q21 chromosome, Aβ transcript encoded by AβPP gene on chromosome 21q21.3, α- Synuclein encoded by a gene (SNCA) on chromosome 4, prion protein (PrP), encoded by a gene (PRNP) on chromosome 20, Transactive response (TAR) DNA-binding protein 43 (TDP-43) encoded by the TARDBP gene on chromosome 1, etc. are few of the examples. Some hereditary associated proteins encoded by genes that are associated with neurological trinucleotide repeat disorders like ataxins, huntingtin, atrophin-1 are also found as a biomarker of disease identification [44]. Protein deposition pattern in CNS during NDDs are classified into several proteinopathies such as cerebral amyloidoses, tauopathies, α-synucleinopathies, prion diseases, trinucleotide repeat diseases, TDP-43 proteinopathies, FUS/FET proteinopathies, neuroserpinopathy, etc. [7, 44, 45, 46, 47]. Only a few numbers of modifications are so far included in the classification and pathological subtyping of the NDDs, e.g. Aβ modification is not included in the classification of AD but the biochemical steps of Aβ aggregation and a different variant of Aβ aggregates have implemented to interpret the early and late phases of AD pathology [48]. Similarly, recent neuropathological studies have revealed that the biochemical classification of tauopathies by analyzing the insoluble and trypsin-resistant tau with varying C-terminal fragments [49]. Tauopathies can be further distinguished by the presence of different ratios of the repeat (R)- and 4R-tau and two or three major phospho-tau bands (60, 64, and 68 kDa) [50]. Other major protein modifications are shown in Table 2.
Proteinopathies
Proteins
Biochemical characteristics
References
Amyloidoses
Amyloid-beta (Aβ)
Produced by proteases mediated the sequential cleavage
Most abundant component of Aβ deposit is Aβ 1–40/1–42 peptides along with other available species such as (Aβ 1–37/38/39)
Disease-associated PrPSc is detergent-insoluble and resistance to protease K treatment but not the physiological cellular form of PrP (PrPC)
PrP can be differentiated based on electrophoretic mobility and N-terminal sequence of the core fragments, and the most common PrPres species is PrP27–30.
Other fragments forms are PrP 11, PrP7–8, PrP14, PrP-CTF12/13, PrP16–17, and PrP17.5–18
Kovacs and Budka, 2009 [8]; Duyckaerts et al., 2009 [45]
Tauopathies
Tau
Most common modification is hyperphosphorylation
Ratio between 3R- and 4R-tau, and two or three major phospho-tau bands (60, 64, and 68 kDa) in Western blot of sarkosyl-insoluble fractions are the major factors for distinguishing tauopathies.
Distinct feature of taupathies are N- and C-terminal truncation, glycation, nitration of tyrosine residues, glycosylation, transglutamination, deamidation; acetylation; oligomer; the banding patterns of C-terminal fragments of tau and the trypsin-resistant band patterns etc.
Lee et al., 2001 [50]; Taniguchi-Watanabe et al., 2015 [49]
Synucleinopathies
α-Synuclein
Modification occur: phosphorylation at serine 87 and 129 and at tyrosine 125 residue
Various conformation and oligomeric states of synuclein are in dynamic equilibrium state.
Biochemical characteristics of some major proteins related to neurodegenerative proteinopathies.
Aβ 1–40/1–42/1–37/38/39 are different amyloids oligomers consisting different numbers of residue-long proteolytic fragments; PrP27–30,PrP 11, PrP7–8, PrP14, PrP-CTF12/13, PrP16–17, and PrP17.5–18 are different fragments of prion protein consisting of different size (Kda) of fragments; Prp-CFT: C-terminal fragments of PrP; PrPSc: abnormal or scrapie isoform of PrP; 3R- and 4R- Tau: 3 or 4C-terminal microtubule binding repeats in Tau protein.
3.3 Cellular pathology
Neurodegenerative diseases can be characterized by the presence of misfolded proteins within or outside of the neurons [51]. Cellular pathology is also an important aspect to distinguish the location of protein deposition at the subcellular level such as nuclear, neuritic (axons or dendrites), cytoplasmic, mitochondria, myelin, lysosomes or in astrocytes, etc. [7]. Charcot–Marie–Tooth neuropathy type 1B (CMT-1B), a hereditary motor and sensory neuropathy, is one such example as it can be identified by the accumulation of misfolded myelin protein zero (mpz) in the endoplasmic reticulum [51]. In superoxide dismutase 1 (SOD1) associated ALS, misfolded SOD1 mutant is found in the cytosol [51]. An aggregate of huntingtin with an expandable polyQ track in the cytosolic and nuclear space of the neuronal cells is a characteristic of HD [52]. α-synuclein, a soluble protein marker of PD is available predominantly in the presynaptic zone of neuronal cells. The complex mechanism of AD consists of binding of Aβ oligomers with several receptors intracellularly. Accumulation of Aβ in the lysosomal compartment followed by a change in its membrane permeability is also identified in AD pathological. Aβ-induced mitochondrial dysfunction by the deregulation of enzymatic activities of the electron transport chain is also identified in AD pathology [52].
4. Diagnosis of NDDs
The NDDs can be largely differentiated by the anatomical regions showing neuronal dysfunction, biochemical and conformational changes in protein markers and neuronal cell pathologies including the deposition of protein(s), and alteration in genetics and epigenetics [53]. Structural neuroimaging techniques such as computed tomography (CT), magnetic resonance imaging (MRI) are used for diagnosis but due to very low specificity, they have been replaced by new neuroimaging techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) [54]. The functional magnetic resonance imaging (fMRI), another new generation diagnostic approach, identify the correlation of different physiological functions during NDDs rather than direct imagining of neuronal activities [55]. The focus of the new diagnostic researches is to establish easily detectable biomarkers from blood or saliva to distinguish the different forms of neuronal disorders [56]. It has been observed by using fluorodeoxyglucose-PET that the earliest sign of AD is metabolic decline. Detection and identification of small molecule metabolites in the biological samples are called metabolomics, which is another newest cutting edge approach for the diagnosis of neurodegenaration associated metabolic disorders [57]. Genetic markers associated with familiar neurodegenerative diseases are already identified for a different type of disorders such as for diagnosis of AD amyloid precursor protein, presenilin gene mutations and apolipoprotein E (APOE) polymorphism are some of the known genetic markers whereas for PD, α-synuclein protein or PrP gene mutation for the familiar type of prion diseases, etc. have been identified, although their sensitivity and specificity are still questionable [58].
4.1 Application of neuro-imaging in the diagnosis of major diseases due to neurodegenerations
The most frequent CNS diseases are diagnosed by using the following functional neuroimaging techniques:
4.1.1 Parkinson’s disease (PD)
PD is known to be progressive as well as a degenerative disorder associated with a loss of dopamine-producing neurons of the substantia nigra and other brain regions [38]. Pathophysiology, progression, and complications of this disease are well understood and identified by neuroimaging techniques. Neuroimaging deals with the detection of the changes in brain structure as well as its region(s) on the basis of changes in brain glucose, oxygen and dopamine metabolism, and receptor binding of dopamine [38]. The functional markers such as (a) the activity of dopa decarboxylase (DDC) terminal, (b) presynaptic dopamine transporters (DAT) availability, and (c) vesicle monoamine transporter density in dopamine terminals (VMAT2) are implemented for neuroimaging (in both PET/SPECT) [38]. DDC works as a catalyst for L-Dopa decarboxylation to Dopamine. Using 6-[18F]-L-dopa PET the activity of DDC can be measured by measuring neuronal loss. 18F-Dopa transfer into 18F-dopamine by amino acid decarboxylase and trapped in synaptic vesicles, whose uptake depends on the presence or loss of nigrostriatal postsynaptic dopamine cell [39, 59]. Similarly, DAT, which helps to clears dopamine after its release in the synaptic cleft, can be used for PD diagnosis. D2–dopamine receptor binding tracers 11C-raclopride-PET and 123I-iodobenzamide (IBZM)-SPECT have been used for the assessment of D2 receptor density and gives good results to evaluate PD patients [38, 39, 59]. VMAT2 is an integral membrane protein which especially transports dopamine like monoamines into synaptic vesicles. 11C-dihydro-tetrabenazine-PET can be used for its test [38]. In PD loss of 5-HT concentration is observed by 11C-WAY100635-PET and the measurement of 5-HT1A receptor by evaluating the functional integrity of serotonergic neurons [59]. fMRI analysis of PD patients has shown the distinct variation in covariance patterns of the region-based resting-state activity in functional brain regional networks in comparison to the normal brain. The detrimental effect of dopamine replacement on non-motor brain functions due to the alteration of the physiological pattern of dopamine signaling can also be proved by fMRI studies [60]. This suggests functional changes between the three different brain-related disorders. PD can be characterized by the activation of the neuroimmune system in microglia followed by a loss of neurons in substantia nigra [61]. 11C-PK11195 is known to enable the detection of increased signals in substantia nigra which reflect local degeneration as a consequence of PD [38]. In addition, the significant reduction in metabolomes like catecholamines [homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC), L-dopa, etc.) has also been observed during PD [62]. NMR metabolomics based study has helped to differentiate PD from non-PD patients by detecting the presence of metabolomes (like creatinine, glucose, lactate, 3-hydroxyisobutyric acid and 3-hydroxyisovaleric acid etc.) in CSF [62]. The presence of kynurenine in the blood of PD is proved to be potential biomarker candidates [62].
4.1.2 Alzheimer’s disease (AD)
Structural neuroimaging with CT and volumetric MRI has an application on AD related cerebral atrophy and measurement of cerebral blood flow or regional glucose and oxygen metabolism [63]. MRI helps to measure the memory forming zone of CNS i.e. hippocampus and cortex-structures in the temporal lobe and further helps to differentiate between AD and other dementia [64, 65]. By using magnetic resonance spectroscopy (MRS) the information about concentrations of tissue substrate or metabolite during AD and MCI (mild cognitive impairment) can be identified by using N-acetyl aspartate as a marker [64, 66]. Quantification of amyloid deposition by tracing the amounts of radioligands in vivo is also possible by PET and SPECT. PET usually detect the metabolic uptake of fluorine 18 [18F]-labeled 2 fluorodeoxyglucose (2-deoxy-2-[18F]- fluoro-D-glucose- FDG) and blood flow in patients with dementia [64, 67]. The fMRI techniques in AD diagnosis is implemented in cerebral blood flow (CBF) and cerebral vasomotor regulation (CVR) mapping. This limitation in CVR has been observed in the APOEε4 gene carrying early-onset AD patients with vascular dysfunction, which occur due to the astrocytic end-feet swelling, degeneration of pericyte, hypertrophy of basement-membrane as well as due to the abnormalities in the endothelial-cell metabolic. Non-invasive fMRI is a major tool for the diagnosis of AD by identifying such changes in CVR mapping [55]. In the AD brain, the most characteristic feature and useful biomarker are amyloid plaques consisting of Aβ protein, dystrophic neuritis, inflammatory factors, and cellular material inside and outside of the neurons [68]. Tau tangles are also associated with AD and composed of paired helical filaments (PHF) derived from abnormally hyperphosphorylated microtubule-associated protein tau [69]. Radiotracers such as [18F]-BAY94–9172, an Aβ ligand, have been used with PET to differentiate between AD and frontotemporal dementia patients [66, 70]. PET studies with the application of [11C] PIB, a derivative of thioflavin-T amyloid dye that binds to Aβ plaques but not tangles, show more retention in the cortical zone of frontotemporal dementic brain when compared to AD brain [64, 65]. 18F-DDNP – PET scanning helps to compare AD, MCI, and controls having intact cognitive functions [71, 72]. The plasma metabolomics biomarkers including glycerophosphatidylcholines, asparagine, acylcarnitines, and asymmetric dimethylarginine (ADMA) are identified as a predictive marker of plasma which can predict the risk of conversion from cognitively normal individuals to AD [57]. Reduction in N-acetyl aspartate in the brain can be correlated with neuronal and mitochondrial dysfunction during AD. Acylcarnitine, sphingomyelins, glycerophospholipids found to be increased significantly in the CSF of AD patients in comparison to normal patients [57].
4.1.3 Huntington’s disease (HD)
HD is a dominantly inherited, autosomal, NDD characterized by motor, cognitive, and emotional abnormalities [42]. In the early course of HD, no structural changes of the brain can be observed by CT and MRI while only in later stage atrophy has been observed in the caudate and frontal cortex [73]. PET study can provide information by diagnosing HD as early as 9 to 11 years before the first symptoms appear [74]. PET with 2-deoxy-2-[fluorine-18]fluoro-D-glucose (18F-FDG-PET) is also used to detect the reduced striatal glucose metabolism in early HD which further causes bradykinesia, dementia, and putamen hypometabolism connects with chorea and eye-movement abnormalities [42, 75]. HD has also been found to be associated with structural loss of dopamine (D1, D2) receptor-expressing medium spiny neurons from the striatum. The damage can be estimated by using radiolabelled dopamine antagonists [11C] raclopride and by observing the binding potential (BP) of dopamine receptors which help to assess the neuronal damage [42]. Further, PET study using [11C] diprenorphine as a tracer has shown a mild loss of opioid receptors in the striatum in HD patients [42]. The accumulation of active microglia due to neuronal loss can be seen with the help of 11C-(R)-PK11195 as a tracer in the striatum, globus pallidus, and frontal cortex in HD patients [76]. fMRI has applied to diagnosed HD by various cognitive paradigm including maze learning, serial reaction time, working memory etc. fMRI blood-oxygen-level-dependent (BOLD) signal response is also applied for correlation between different regions in HD patients [74]. HD is associated with metabolic and energy pathways alterations. After studying various metabolomics Mastrokolias et al. [77] have found that the deregulation of phosphatidylcholine metabolism is a prominent plasma biomarker of HD.
4.1.4 Amyotrophic lateral sclerosis (ALS)
ALS is a motor neuron disease (MND) associated with progressive deterioration of the corticospinal tract, brainstem, and anterior horn cells of the spinal cord [78]. Cortical atrophy is observed in late ALS which can be assessed by structural MRI of ALS patients’ CT studies. The increased population of microglia during ALS can be observed by radiolabelled PET ligand [11C] (R)- PK11195 which selectively binds with the peripheral benzodiazepine binding site (PBBS) of microglia [79]. ALS can be also diagnosed by the measurement of postsynaptic dopamine D2 receptor binding abilities. 123I-benzamide (123I-IBZM), a specific binding substance with D2 receptors shows less receptor binding during ALS when investigated using SPECT [80, 81]. PET studies show a decrease in 11C-flumazenil (a radiolabelled antagonist of benzodiazepine receptor) binding in the primary sensory, premotor, prefrontal, thalamic, and parietal regions during ALS [78, 82]. Both 123I-N-isopropyl-p-iodoamphetamine (123I-IMP) and 99mTc-hexamethyl propylene amine oxime ([99mTc] –D, L- HMPAO) are markers which have been used to determine reduced fronto-temporal blood flow as well as glucose metabolism by SPECT studies [41].
4.1.5 Multiple sclerosis (MS)
MS is characterized by demyelination of neurons in the CNS, with the formation of plaques or lesions [43]. MRI studies show these lesions are dynamic in different stages of the disease. Neuronal loss and brain atrophy are not visible in the early stage of MS by MRI scans [83]. Decreased regional and global CBF and cerebral metabolic rate of glucose (CMRglc) can be observed by PET imaging using 18FDG as a detection agent. Although the differentiation between acute and chronic MS is tough for the SPECT study with the help of Tc-99 m-MIBI as a radiopharmaceutical, which in fact shows multiple accumulation points in acute MS but not in chronic MS [84]. Binding potential of microglial peripheral benzodiazepine binding sites (PBBS) towards [11C] (R)-PK11195 can be applied as a determinant factor of MS, like other neurodegenerative diseases [83, 85]. Application of fMRI in MS has been recently applied to assess MS-associated modification of cervical cord in the patient. This study also helps to identify the brain regions involved in the tactile and proprioceptive stimulation during AD pathology [86]. Mangalam et al. [87] have performed a study to find out the MS-based untargeted metabolic alterations in bile acid biosynthesis as well as the metabolism of histidine, taurine, tryptophan linoleic acid, and d-arginine.
4.2 Anatomical identifications of neuronal losses in relation to clinical symptoms
Identification of anatomical positions is needed for understanding the early symptoms. For example, brain regions such as the entorhinal cortex, neocortex, hippocampus, limbic system are responsible for symptoms like cognitive decline, dementia, and other high-order brain functions alterations whereas basal ganglia, thalamus, brain stem, and motor cortical areas are mostly responsible for disturbance in body movements. Combinations of these types of symptoms are mostly observed during the progression of diseases following region-specific neurodegenerations [7]. One of the conventional approaches to understand neuroanatomy is brain mapping which helps to localize the disease-related changes [88, 89]. Characterization of brain regional anatomical changes in diseased conditions is a fascinating and advanced approach of current neuroscience research [90]. Earlier the identification of neurofibrillary tangles in the cortex and the hippocampus due to Alzheimer’s were studied by region-of-interest technique (ROI). These techniques (ROI) can be implemented to compute the overall volume for a particular brain structure, based on the manual or automatic positioning of the sections’ MRI serially for a subject by using already existing anatomical protocols [91]. Though the prior knowledge of anatomical structures makes ROI-based analysis a strong and useful approach, the lack of detailing in the investigation of the underlying complex structure makes this method less advantageous for diagnosis [92]. Like in AD patient ROI technique is capable of establishing the hippocampus and entorhinal cortex as most prominent imaging biomarkers but this technique is not useful to investigate the underlying complex structure of the hippocampus for further diagnosis [91, 92, 93]. Another newer image analysis technique is Voxel-based morphometry (VBM) able to identify cortical and subcortical degeneration simultaneously, providing significant insight changes in gray matter in AD and MCI [94]. VBM can be implemented to classify MRI maps into individual maps of gray matter, white matter, and CSF tissue classes followed by creating an alignment of gray matter maps and then smoothened it with the help of filters. The corresponding cognitive score has been statistically assessed using multiple regression analysis. The general linear model used to fit with gray matter density at each image location or voxel related to diagnosis, cognitive scores, etc. [95, 96]. Several brain regional gray matter atrophy such as temporal, posterior cingulated, precorneal cortex in AD and normal aged persons has been documented by using VBM studies [97]. The application of VBM has also been observed to investigate the effect of aging and gender on spatial profiling in normal subjects [96] as well as in the frontotemporal zone of PD, and Lewy body dementia, and also in herpes simplex encephalitis [98, 99, 100].
The limitation of VBM is inherently low spatial resolution due to spatial smoothening to achieve inter-individual cortical variability [101]. VBM study is also not optimal for analysis of gray matter atrophy as highly convoluted features that appeared for the Gyral and sulcal region cannot be readily distinguished leading to a lack of detecting and localizing the subtle cortical differences [89].
4.3 Brain mapping: a diagnostic tool for neurodegenerative diseases
Brain mapping techniques rely on a mathematical computation of anatomy where brain surface and its volumes are represented as 3D complex geometrical patterns mesh models, averaged, combined across subjects and can be statistically defined [89]. The technique implies transformable and deformable templates which can be transformed into brain shape for studies by constraining surface landmarks (e.g., sulci) or alignment of surface-specific geometrical patterns (e.g., gyri) and helps to co-localized cortical and subcortical regions along with cortical thickness, gray matter density, functional activations, etc. by improving the identification of cortical and subcortical changes associated to the diseases [102]. Localization of changes by cross-sectional and longitudinal imaging is done by tensor-based morphometry (TBM), a newer approach to map the changes in the brain over time. This method has been found to be sensitive, with high throughput, and attractive for gauging brain changes in larger study populations. In cross-sectional studies, where many individual images are matched to a common brain template to compare the systematic volume and shape between control and diseased individuals, TMB has been found to be effective and helps to clinically correlate the different disease conditions like Fragile X syndrome 56 and Williams syndrome, etc. [103]. TBM can detect and visualize subcortical nuclear as well as structural gray and white matter by using newer statistical methods [103].
4.3.1 Application of brain mapping in AD
Radial atrophy mapping of the hippocampus has been first applied by Thompson et al. [104] for the diagnosis of AD and has shown distinct differences between normal elderly and AD patients. Later on, Frisoni et al. [105] have demonstrated that the CA1 area and parts of the subiculum using the same technique and showed AD cases have 15–20% atrophy in relation to the normal controls. Apostolova et al. [88] have shown that patients with MCI have more severe involvement of CA1 and subiculum atrophy which are likely to convert into AD at a later age. Apolipoprotein E4 (APOE ε4) a prominent genetic risk factor for sporadic AD carriers, has a higher hippocampal atrophy rate than non-carriers as observed by longitudinal MRI study. Further, Bookheimer et al. [106] by cortical thickness study have shown that cognitively normal APOE ε4 carriers have a significantly thinner entorhinal cortex and focal hippocampal atrophy in comparison to normal non-carriers. Thompson et al. [104] have also reported based on the comparison of baseline grey matter density map a significant atrophy in lateral, temporal, parietal, and parieto-occipital cortices in AD patients. Brain mapping by computational anatomy techniques has significantly improved sensitivity for the detection of differences in the disease-induced groups. The study between amnestic MCI and mild AD subjects has shown a highly significant greater cortical atrophy in AD patient despite a small cognitive difference between these two groups [88]. It has also been observed that in sporadic early-onset of AD (EOAD; <65 years of age) and late-onset of AD (LOAD; >65 years of age), subjects can also be differentiated by severity and localization of cortical atrophy. While EOAD shows widespread atrophic changes, LOAD subjects show lower rate and more focal pattern of entorhinal, para-hippocampal, inferior temporal, posterior cingulate/precuneal, and lateral temporal changes, suggesting younger AD subjects have displayed higher cognitive reserve and tolerance to pathological burden as cortical neurodegeneration correlates with cognitive declines [105].
4.3.2 Application of brain mapping in dementia
Dementia with Lewy bodies (DLB) is associated with some of the features such as cognitive decline, early-onset hallucinations and delusions, Parkinsonism, and a fluctuating course. Pathologically hallmarks for DLB are synuclein-rich intracellular deposits known as Lewy bodies is often observed as a hallmark of DLB in patients as well as in few cases of AD. It has been observed that a distinct cortical atrophy pattern i.e. hippocampal and inferior temporal preservation along with midbrain atrophy occurs in DLB but not in AD when studied by VBM [100]. Ballmeier et al. [107] have mentioned that the preservation of the temporal and orbitofrontal cortices in demented subjects is also a distinct feature of DLB.
5. Preventive measures for neurodegenerative diseases
The estimated number of total dementia cases globally is around 50 million among which 60% of the cases are from low or middle-income countries and also 10 million new cases are reported globally every year as per the recent report of WHO. Hence, the demands of health care and social services are huge and need constant surveillance to decrease the rate of incidence of this type of life-threatening diseases as well as its associated expenses. It has been observed that up to 10 years before the diagnosis of dementia, cognitive impairment is likely to appear in individuals and it declines sharply in the final stage of 3 years [108]. Individuals with deficits in vitamin B12, folate, and thyroid-stimulating hormones (TSH) are found to involve with poorer cognitive performances [109]. Elevated levels of serum-homocysteine and cardiovascular diseases are also responsible for cognitive impairments [110]. Depressed mood, hip fracture, polypharmacy, history of psychoses are the reasons behind cognitive impairment without dementia (CIND) in older age and the low education, depression, APOE ε4 allele, medicated hypertension, midlife elevated serum cholesterol, and high diastolic pressure, as well as diabetes and anticholinergic medication, are responsible factors for mild cognitive impairment (MCI) [111, 112]. The strongest risk factor of dementia and AD is age and lifetime cumulative multiple risk factors like genetic susceptibility, environmental exposure, and biological factors etc. are also needed to be considered for identification of preventive measures [113, 114]. For example, genetic and environmental factors are responsible for Familial AD as reported by many and found to be happening in 58% of AD cases [114, 115]. The involvement of APOE ε4 allele as a genetic factor as well as some other genes in AD is well established and, APOE polymorphism can partially explain the familial aggregation of AD in 15–20% of AD cases which generally affect 75 years or older patients [116, 117]. Vascular risk factors and AD or dementia are also found to be associated and the control of amendable vascular disease-associated risk factors has found to offer preventive measures for AD [118]. Such as controlling high blood pressure, diabetics, and mid-life obesity are important interventions and found to show a better score in cognitive tests and reduce the risk of dementia and AD in very old individuals [118]. One more important aspect is psychosocial factors and it has been reported that attending higher education in early-life, work complexity in adult life, intellectually stimulating activities are also found to help in delaying the onset of dementia [119]. Physical activities have a beneficial effect on mental health [120]. It has been reported by Alzheimer’s associations [120] that mentally, physically and socially active lives have the potential to postpone the onset of clinical dementia by 5 years and substantially decrease the number of dementia cases in the community.
5.1 Role of diets and micronutrients in the prevention of neurodegenerative diseases
Dietary components are found to be effective in the prevention of neurodegenerative diseases [121]. It has been observed that docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid, enriched diet such as fish (fatty or blue species), shellfish, and algae [122] plays a relevant role in the preservation of histopathology of the neuronal tissue and helps in memory and learning maintenance [123]. Apart from that, polyphenols, curcumin like food components have neuroprotective properties [124, 125]. Polyphenols are a natural antioxidant and show activities on chelation, scavenging free radicals, survival gene activations, cell signaling pathways, and also regulating mitochondrial function by the ubiquitin-proteasome system [124]. On the other hand, curcumin is an anti-amyloid drug and responsible for reducing oxidation of protein and also reduce pro-inflammatory cytokines interleukin-1beta in AD-induced transgenic mice brains [125]. Deficiency of vitamin B, C, and E are associated with AD development [126]. Some mixed results in this regard have been observed in several clinical studies [127, 128]. As reported, a lower level of dietary and supplemented folic acid is associated with AD pathology and lack of folic acid due to malabsorption and malnutrition can increase the chance of AD by two folds in the elderly [127, 129]. Some studies have found no significant role of Vitamin B9, B12, C, E in AD pathology, whereas the other study gives evidence that Vitamin C and E have a neuroprotective effect on AD [128]. It has also been studied that while sufficient intake of vitamin E, omega-3 fatty acid and omega-6 fatty acid, vitamins A, C, and whole grains increase neuronal activation, food component like saturated fatty acids, cholesterol and sodium significantly lower the neuronal activation and gray matter volume [130]. One more significant effect of diet on neuronal health is observed when a calorie-restricted diet is consumed by aged individuals [131]. It has observed that calorie restriction augments brain-derived neurotrophic factor (BDNF), induces sirtuins a silent information regulator proteins responsible for the regulation of life span, repair, and protection of DNA, etc. [132]. While some dietary components’ actually have the preventive function on neurodegeneration on the other hand some obesity-induced dietary components act oppositely and increase the risk of AD, PD, and neuroinflammatory disease [133].
5.2 Physical exercise for prevention of neurodegenerative diseases
Physical exercise for short term or long term has been found to be beneficial on neurodegenerations and cerebrovascular diseases as observed in both animal and human model [134]. Physical exercise and the expression of different neurotrophic factors [like BDNF, insulin like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF)] are found to be associated, and hence promote neural plasticity and neurogenesis in the hippocampus [135]. It has also been observed that upregulation of BDNF in circulation as well as in the brain can be induced by exercise which can be corroborated with an increase in cognitive function [135]. Due to exercise metabolite-like ketone bodies accumulates in the hippocampal region of the brain which alters BDNF promoter and promotes BDNF expression [136]. BDNF expression is regulated by various genetic factors and pathways like Val66Met mutation [137], PGC-1α/FNDC5 pathway [138], APOEε4 allele carriers [139] and methyl CpG binding protein 2, etc. [140]. Reports are also available on the effect of exercise-induced increase level of VEGF in relation to the reduction in ischemic injury and improvement in cognitive performance. This may be due to an increase in progenitor cell proliferation and all the cell differentiation in ischemic penumbra [141]. Some data has depicted that exercise-induced muscular VEGF increases the level of VEGF in the hippocampus. However, this VEGF helps in neurogenesis and angiogenesis in the ischemic brain followed by improved cognitive activity [142]. The muscle-derived IGF-1 has been found to increase IGF-1 permeability via BBB by increasing the IGF-1 receptor expression in BBB followed by IGF-1 concentration in the hippocampus possibly by regulating IGF binding proteins (IGF-BPs) [143]. Alteration of cytokine production by exercise can also restore the IGF-1 level followed by a reduction in neurodegeneration [143]. Physical exercise, as reported, when used as an adjuvant therapy of psychotropic drugs gives better anti-depressant and anti-anxiety outcome and also effectively reduces dementia [144]. Production of several myokines in muscles (like PGC-1α, Irisin and Cathepsin B, etc.) is promoted by exercise. Myokines that are beneficial for the brain (fibroblast growth factor 21 (FGF-21) and SPARC etc.) also generate after exercise. Serotonin (5-HT) concentration generally increases after exercise in serum, whole blood, and also in urine [145]. This peripheral 5HT level is found to be correlated with an increased level of 5-HT in the brain [146]. Exercise is also associated with a decrease in AD specific deposition of Aβ and tau pathology in the brain [147]. High-intensity exercise provides an improvement in PD associated impaired motor functions [148]. Exercise can also reduce the loss of dopaminergic neurons and fibers and decrease α-synuclein in the nigrostriatal region as observed in animals [149].
6. Therapeutic strategies
Conventional therapies such as cholinesterase inhibitors for AD or Levo-dopa for PD provide symptomatic relief but not on effective disease progression. Advancement in the knowledge of the neuro-molecular mechanism of NDDs has helped to develop new drugs to counteract pathological aggregation of the protein [150]. The prevention of abnormal protein aggregation or targeting of misfolded proteins for their degradation by new therapeutic agents is a potential field of recent researches [151]. Reports are also available on the inhibition of fibril formation by several compounds like antibodies, molecular chaperones, nanoparticles of polyphenols, metal chelators, and tetracyclines nanoparticles by inhibiting the aggregating pathways of different amyloidogenic proteins, such as Aβ, α-synuclein, PrP protein, etc. [152]. But the most challenging part of therapeutic strategies are (a) prevention of the formation of oligomers or converting aggregation process into alternative non-toxic pathways (b) transporting the therapeutic agents through the blood–brain-barrier (BBB) and (c) delivery of nanoparticulate drugs to the targeted neuron to reduce dose-dependent toxicities and side effects.
6.1 Available treatment paradigm
Among the few food and drug administration (FDA) approved drug regimen Donepezil and Rivastigmine like acetylcholine esterase inhibitors are used as palliative treatment which help to reduce the progression of AD but not for the long-term [36, 153]. A combination of levodopa and carbidopa has been successfully delivered via the BBB to treat PD patients. The drugs act by converting into dopamine after decarboxylation in the substantia nigra of the PD patient and increase the level of dopamine in that zone for the first few years of treatment after consecutive consumption [40]. Dopamine agonists such as Pergolide, Bromocriptine Parlodel also have therapeutic efficacy but show cardiovascular and endocrinological problems [154]. In HD, reserpine, or dopamine receptor blockers (i.e. phenothiazines) are used to impair dopamine transport and to reduce overactivity in dopaminergic nigrostriatal pathways [155]. In MS, the preventive measures taken to combat the relapse are prednisone to reduce inflammation, beta-interferon, Ocrelizumab, glatiramer acetate, alemtuzumab, mitoxantrone for immunomodulation, and Ocrelizumab for reducing the primary progression [156].
6.2 Future strategies
Effective treatment of NDDs needs identification and mitigation of risks, complete cure, or at least a long term relief from the symptoms that need to be achieved despite all the advancement of genetic, biomolecular, and pharmaceutical sciences. Some of the strategies are designed or may execute in lower animals but clinical trials and human applications are yet to be achieved. Some novel therapeutic strategies are summarized below.
6.2.1 Inhibition of disease-associated protein deposition
Protein misfolding are occurred due to gene mutations, oxidative stress, aging, altered cellular temperature, pH, etc. [157]. The misfolded proteins are often partially unfolded by molecular chaperones and then go through a self-rearrangement to form oligomeric aggregates that are finally converted into amyloid fibrils [158]. Accumulations of such protein aggregates are often found to be in relation to amyloidosis of the CNS as well as symptoms of neurodegeneration [159]. Synthetic chaperons or short peptides with a recognition motif of misfolded proteins have therapeutic potential to disaggregate this protein aggregation during amyloidosis. Heat shock protein 104 (Hsp104) one of the major molecular chaperones, has been found to be efficacious to disaggregate proteins aggregates in yeast cells [160]. Hsp104 has shown to eliminate various amyloid conformations and reduce deposits of pre-amyloid oligomers by binding with the protein fibril and blocking the aggregation process [160]. One variant of Hsp104 has properties to dissolve α- synuclein aggregates in the PD model. Hsp70 and its related compound also have neuroprotective roles as found by in-vitro and in-vivo studies (Figure 2) [160]. Hsp70 is also responsible for restoring Tau homeostatic [161]. In-vitro and in-vivo studies have revealed that Hsp70 and related compounds help to clear Aβ depositions and restore Tau homeostasis [160, 161]. The proposed therapeutic strategies are tabulated in Figure 2. HD is associated with polyQ induced misfolding of mHTT mutant Huntington which can be the target and inhibit by Hsp70 [162]. Curcumin or epigallocatechin gallate have Hsp70 simulating properties resulting in a reduced level of neuronal death followed by improved cognitive and motor deficits [163]. On the other hand, α-synuclein misfolded protein aggregation is associated with PD, and Hsp70 can bind with α-synuclein and halt the further misfolding of α- synuclein followed by refolding [164]. In this context, it may be mentioned that specific Hsp and related chaperones significantly contribute to targeting protein aggregates (mHTT, α-synuclein, etc.) specific to NDDs, and the development of these Hsp stimulant can be beneficial for future therapies [165].
Figure 2.
Different strategies for inducing Hsp 70 as molecular chaperone in AD brain.
6.2.2 Neuroimmunomodulatory therapies
Neuronal death and neurodegeneration are in connection with the vicious cycle of inflammation especially when inflammatory mediators stay in the tissue for a longer period. AD, PD, and HD cases express higher plasma and CSF concentrations of proinflammatory cytokines, such as IL-6, TNF-α, IL-1β, IL-2, IL-6, and cyclooxygenase-1/2, etc. [166] whereas, anti-inflammatory cytokines and growth factors (IL-10, TGF-β, CD206, etc.) producing microglia becomes lower in number in such patients [167]. The monocytes isolated from the carriers of the HD gene, express the mutant Huntingtin protein and show hyperactivity to lipopolysaccharide stimulations [168]. Thus, it may be concluded that the hyperactive immune system is an important feature of HD pathogenesis and its associated immunomodulators can be used for potential HD treatment. The presence of CD8+ and CD4+ peripheral lymphocytes in substantia nigra has been found in post mortem brains of PD patients [169]. Anti-inflammatory drugs such as minocycline, resveratrol, tanshinone, and silymarin have therapeutic promises against PD by blocking the activation of NADPH oxidase and microglial activation and pro-inflammatory cytokine release [12, 157]. Apart from that, it has also been investigated that the monoclonal antibodies against the α-synuclein not only reduced protein propagation and amyloid formation [170] but also ameliorated dopaminergic neuronal cell loss and improved PD-like pathologies, followed by improving motor deficits in PD induced mouse [170].
6.2.3 Autophagy
Neuronal cells are subjected to autophagy but they have a very strong lysosomal system which is effective for the removal of protein aggregates and dysfunctional mitochondria as well as the rapid removal of the autophagosomes [171]. The autophagy regulating gene mutation often leads to NDDs like AD, ALS, and PD as a consequence of large gathering of the debris of dysfunctional organelles and undiluted waste proteins [172]. The factors responsible for the suppression of autophagy followed by suppressing neuronal functions and plasticity are stress signals, hypoxia, mechanical damages, decreased level of amino acids, etc. [173]. Mutation of autophagy-related genes has shown neurodegeneration in lower animals like mice and flies [174, 175]. A promising therapeutic strategy is a drug-induced autophagy in neurogenerative patients for the removal of abnormal proteins as observed in animal models. One of the recent examples of such drug-induced autophagy is methyl-4-phenylpyridinium (MPP+) which induces apoptosis in dopaminergic neurons by disrupting the complex I of the electron transport chain of mitochondria of mouse Parkinson’s Models [176]. Similarly, the antihistaminic drug, Latrepirdine shows a regulation of APP in the AD mice model [177]. Drugs like calcium channel blockers and USFDA approved rapamycin show potential to stimulate the autophagic process followed by the clearance of mutant huntingtin protein in lower animals [178]. Rapamycin is also able to reduce Aβ-induced cognitive deficits of AD by activation of the AMPK-mTOR signaling pathway in aged as well as Type 2 Diabetes Mellitus-induced AD cases [179]. mTOR signaling has the ability to form autophagic vacuoles, mitigating tau and Aβ deposition and controlling the apoptotic pathways. Metformin has been found to involve in autophagy by AMPK-dependent mechanism of HD as well as dephosphorylates neurofibrillary tangles of tau in AD and is established as a potential therapeutic agent for NDDs [177].
6.2.4 Neurotrophic factors and possible strategies for neurogenesis
Dysregulation of the neurotrophic factors which are the molecular aids of neuronal functions such as differentiation, growth, etc., is associated with NDDs [180]. The affected region of the brain starts losing neurons and glia in absence of functional regulation of these molecules [181]. Some Factors such as nerve growth factors (NGF), BDNF have the ability to bind with tyrosine receptor kinases, inhibit apoptotic signals, and promotes cell survival by promoting tissue growth by cell proliferation [182] and also their absence play a prominent role in neurodegenerative diseases [183]. A decreased level of NGF in AD patients induces cellular death followed by loss of neuronal functions whereas a decrease of BDNF in substantia nigra does the similar in PD patients due to degeneration of synaptic connections [184]. An increase in the level of these neurotrophic factors in the degenerated brain regions could be a possible therapeutic strategy although their larger size and polar nature make them unsuitable for transport through BBB and difficult to target [185] although gene delivery injection and neurotrophin mimetics are already under investigations [183]. Another important marker of NDDs is the deficiency of neurosteroids during AD [37], PD [37], HD [186], and MS [187] which can be defended by hormonal replacement therapy and found to be beneficial in AD, PD, HD, and MS patients [188].
6.2.5 Insulin associated neurodegeneration
Insulin signaling in CNS is responsible for differentiation, proliferation, neurite growth, and shows neuroprotective as well as anti-apoptotic activity [189]. The structural and functional integrity of synapses, neurons, and neuronal circuits followed by memory and learning are depend partially on Insulin and affected by diabetes mellitus and metabolic syndromes [189]. Insulin resistance in the brain is also associated with an increased level of phospho-Tau and Aβ42 [189]. Evidence is there of decrease in levels of insulin in the brain and CSF during AD with an increase in Aβ42 and advanced glycation [189]. Insulin administration enhances Aβ42 clearance and improves working memory and cognition [189]. Insulin receptor-associated genes IRS-1 pSer616 and IRS-1 pSer636/639 have been identified in relation to Aβ oligomer levels and function as a biomarker for AD [190]. Antidiabetic drug Metformin is reported to inhibit cognitive decline which may have some connection with the insulin signaling pathway in CNS although needs further investigation [191].
6.2.6 Cholinergic system in AD
The connection between the cholinergic system and AD has been hypothesized as presynaptic cholinergic markers are found to be depleted in the cerebral cortex during AD pathology [192], nucleus basalis of Meynert (nbM) in the basal forebrain undergoes severe degeneration in AD [193], and memory gets weaken by the cholinergic antagonist while agonists have the opposite effect [194]. Cholinesterase inhibitors such as donepezil, rivastigmine, and galantamine have been found to improve significantly the cognitive activity related to AD [195].
6.2.7 Targeting oxidoreductases
A very limited information are available about targeting oxidoreductases to inhibit the proteinopathies and consequent neurodegeneration. Among the free radical generator, the NOX bears a significant role in oxidative stress-induced neurodegeneration. The pharmacological NOX inhibitors have been found to improve different NDDs and it is well-reviewed by Barua et al. [196]. The PDI, as discussed before is associated with different proteinopathies (like AD and PD) and its attenuation could be a promising approach to counteract the proteinopathy-induced neurodegeneration. Polyphenols curcumin, from a turmeric (Curcuma longa) spice and masoprocol (from Larrea tridentata), have found to restore the ROS-induced chaperone damage, protein misfolding, and thereby neurodegenerative disease, sustaining traffic along the ER’s secretory pathway by preserving functional integrity of PDI [197].Nrf-2 also an important transcription factor, associated with the oxidoreductase system is also a crucial target to deal with. Naringin (4′,5,7-trihydroxy flavonone 7-rhamnoglucoside), the flavonone found in grapefruit and related citrus species has been found to upregulate the Nrf-2 and its consequent cytoprotective genes to act as a neuroprotective molecule [198]. Carnosine, an endogenous dipeptide biomolecule has been recently found to be a potent inhibitor of aging-induced increase in brain regional monoamine oxidase-A activity [26] and it can also reduce and restore the aging-induced deposition of amyloid-beta plaque quantitatively as well as qualitatively [199, 200]. Interestingly, the inhalation of patchouli oil (extracted from the leaf of Pogostemon cablin) has also the ability to modulate the blood platelet MAO-A activity and thereby in mood behavior [201].
6.2.8 Epigenetic modulations
Epigenetic markers such as histone deacetylases have been proved to be involved with AD. Treatment with HDACi (histone deacetylase inhibitors) such as sodium butyrate, phenylbutyrate, suberoylanilide hydroxamic acid, resveratrol induces phosphorylation of tau protein, reduces the amyloidogenic processing of APP followed by restoration of learning and memory deficits in AD patients [202]. PD is also associated with epigenetic modulation. Where sporadic PD patients are linked with α-synuclein hypomethylation in dopaminergic neurons, the familial PD patients show a decrease in histone acetylation followed by an increase in α-synuclein levels [203]. α-synuclein-mediated neurotoxicity has been found to reduce by the treatment with Sirt2 siRNA [204]. A decrease in PD symptoms with the administration of dopamine may also be correlated with the deacetylation of histone H4 lysine 5 (H4K5), histone H4 lysine 12 (H4K12), and histone H4 lysine 16 (H4K16) [205].
7. Conclusion
The NDDs are progressive neuronal cell deaths due to environmental, biochemical, genetic and epigenetic factors. Generation of free radicals due to the oxidoreductase activity and deterioration of antioxidant system are found to trigger the aggregation of misfolded proteins in CNS causes mitochondrial dysfunctions and neuro-inflammations which finally leads to NDDs (Figure 3) [2]. Based on the predominant pathological features, NDDs can be classified in three different way, i.e. (a) anatomical, (b) the proteins undergoing conformational and biochemical modifications and (c) cellular pathology. Protein deposition pattern in CNS during NDDs are classified into several proteinopathies such as (a) cerebral amyloidoses, (b) tauopathies, (c) α-synucleinopathies, (d) prion diseases, (e) trinucleotide repeat diseases, (f) TDP-43 proteinopathies, (g) FUS/FET proteinopathies, (h) neuroserpinopathy, etc. depending upon the major protein aggregates [8, 44, 45, 46]. The diagnosis of neurodegenerative diseases is mostly associated with quantification of their specific receptor binding, changes in cellular metabolism or in anatomical structure. The neuroimaging techniques such as PET, SPECT, fMRI etc. have been extensively used to diagnosed receptor activities and metabolic faith of damaged neuronal cells during diseased condition by using radio labeled tracers. Applications of metabolomics is another newer approach for the diagnosis and prognosis of NDDs. On the other hand, the characterization of brain regional anatomical changes in diseased conditions can be performed by brain mapping techniques. These advancements of technologies made the diagnosis of neurodegeneration much easier and an early diagnosis is also possible to some extent for most of the major NDDs. Although complete cure from NDDs/neurodegenerative disease(s) is not yet achieved but therapies that can prevent the early occurrence of NDDs are investigated. Individuals’ deficits of vitamin B12, folate, and thyroid-stimulating hormones (TSH), cardio vascular and metabolic disorders, genetic and environmental factors are few of the reason behind NDDs and can be prevented by taking proper measure from the early life. Physical exercise, calorie restriction and few dietary components like DHA, polyphenols have neuroprotective effect and found to be beneficial for NDDs. Apart from prevention, there are limited medicated therapies are available in the market for the treatment of NDDs. But many strategies like inhibition of disease-associated protein deposition, immuno- modulatory therapy, treatment with neurotrophic factor, epigenetic regulation, targeting oxidoreductases, and insulin therapy are under investigations and clinical trials. The current advancement in biochemical, pathological and pharmaceutical researches may ensure a better future of global neuronal health but it needs adaptation of a healthier lifestyle from the early day of life to avoid the occurrence of such NDDs.
Figure 3.
Schematic representation of overall causes, diagnosis, prevention and therapy of NDDs. The preventive measures are able to prevent the early causes of NDDs, while the diagnosis and therapy at later stage target and try to control the diseased condition due to NDDs. ROS: Reactive oxygen species; RNS: Reactive nitrogen species; PET: Positron emission tomography; SPECT: Single photon emission computed tomography; ROI: Region of interest; VBM: Voxel-based morphometry. + and - indicate activation and inhibition respectively.
Acknowledgments
The authors are thankful to the Department of Pharmaceutical Technology, Jadavpur University, Kolkata; University Grants Commission (UGC), New Delhi; Science and Engineering Research Board (SERB), Govt. of India; Indian Council of Medical Research (ICMR), New Delhi, India; Department of Psychology, Neuroscience Program, Central Michigan University, Mount Pleasant, Michigan, USA for their support to prepare the present work.
Conflict of interest
There is no conflict of interest to declare.
\n',keywords:"neurodegenerative disorders, proteinopathies, oxidoreductase, neuroimaging, brain mapping, neurotrophic factors, neuroinflammations, epigenetic modulations",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/74857.pdf",chapterXML:"https://mts.intechopen.com/source/xml/74857.xml",downloadPdfUrl:"/chapter/pdf-download/74857",previewPdfUrl:"/chapter/pdf-preview/74857",totalDownloads:52,totalViews:0,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,dateSubmitted:"September 6th 2020",dateReviewed:"November 9th 2020",datePrePublished:"January 27th 2021",datePublished:"February 17th 2021",dateFinished:"January 18th 2021",readingETA:"0",abstract:"Neurodegenerative disorders (NDDs) are a broad range of pathological conditions which target the neurons, creating problems in movements and mental functions. The NDDs have drawn a lot of attention among the diseases because of its complexity in causes and symptoms, lack of proper effective treatment(s), no report of irreversibility, and poor impact on social and financial aspects. Individual’s vulnerability towards the stress-related biochemical alterations including increase in oxidase enzymes’ activities and generation of free radicals, abnormal protein dynamics, mitochondrial dysfunctions, and neuroinflammation often lead to degeneration of neuronal cells. Some advanced techniques are now able to detect the development and progression of different NDDs’ complications. The current focus of research on NDDs is to establish convenient therapeutic strategies by targeting different aspects including upliftment of cellular defense mechanisms, especially oxidoreductases as a protective tool. This chapter focused on those updated information on the development, diagnosis, prevention, and therapeutic strategies of NDDs.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/74857",risUrl:"/chapter/ris/74857",book:{slug:"oxidoreductase"},signatures:"Mrinal K. Poddar, Apala Chakraborty and Soumyabrata Banerjee",authors:[{id:"318618",title:"Emeritus Prof.",name:"Mrinal K.",middleName:"Kanti",surname:"Poddar",fullName:"Mrinal K. Poddar",slug:"mrinal-k.-poddar",email:"mrinalkp@yahoo.com",position:null,institution:null},{id:"318620",title:"Dr.",name:"Soumyabrata",middleName:null,surname:"Banerjee",fullName:"Soumyabrata Banerjee",slug:"soumyabrata-banerjee",email:"soumyabrata29@gmail.com",position:null,institution:null},{id:"338670",title:"Ms.",name:"Apala",middleName:null,surname:"Chakraborty",fullName:"Apala Chakraborty",slug:"apala-chakraborty",email:"apala3pharma@gmail.com",position:null,institution:{name:"Jadavpur University",institutionURL:null,country:{name:"India"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Role of oxidative stress in neurodegenerations",level:"1"},{id:"sec_2_2",title:"2.1 Role of oxidoreductase in NDDs",level:"2"},{id:"sec_4",title:"3. Types of neurodegeneration",level:"1"},{id:"sec_4_2",title:"3.1 Anatomical classification",level:"2"},{id:"sec_5_2",title:"3.2 Based on conformational and biochemical modifications of proteins",level:"2"},{id:"sec_6_2",title:"3.3 Cellular pathology",level:"2"},{id:"sec_8",title:"4. Diagnosis of NDDs",level:"1"},{id:"sec_8_2",title:"4.1 Application of neuro-imaging in the diagnosis of major diseases due to neurodegenerations",level:"2"},{id:"sec_8_3",title:"4.1.1 Parkinson’s disease (PD)",level:"3"},{id:"sec_9_3",title:"4.1.2 Alzheimer’s disease (AD)",level:"3"},{id:"sec_10_3",title:"4.1.3 Huntington’s disease (HD)",level:"3"},{id:"sec_11_3",title:"4.1.4 Amyotrophic lateral sclerosis (ALS)",level:"3"},{id:"sec_12_3",title:"4.1.5 Multiple sclerosis (MS)",level:"3"},{id:"sec_14_2",title:"4.2 Anatomical identifications of neuronal losses in relation to clinical symptoms",level:"2"},{id:"sec_15_2",title:"4.3 Brain mapping: a diagnostic tool for neurodegenerative diseases",level:"2"},{id:"sec_15_3",title:"4.3.1 Application of brain mapping in AD",level:"3"},{id:"sec_16_3",title:"4.3.2 Application of brain mapping in dementia",level:"3"},{id:"sec_19",title:"5. Preventive measures for neurodegenerative diseases",level:"1"},{id:"sec_19_2",title:"5.1 Role of diets and micronutrients in the prevention of neurodegenerative diseases",level:"2"},{id:"sec_20_2",title:"5.2 Physical exercise for prevention of neurodegenerative diseases",level:"2"},{id:"sec_22",title:"6. Therapeutic strategies",level:"1"},{id:"sec_22_2",title:"6.1 Available treatment paradigm",level:"2"},{id:"sec_23_2",title:"6.2 Future strategies",level:"2"},{id:"sec_23_3",title:"6.2.1 Inhibition of disease-associated protein deposition",level:"3"},{id:"sec_24_3",title:"6.2.2 Neuroimmunomodulatory therapies",level:"3"},{id:"sec_25_3",title:"6.2.3 Autophagy",level:"3"},{id:"sec_26_3",title:"6.2.4 Neurotrophic factors and possible strategies for neurogenesis",level:"3"},{id:"sec_27_3",title:"6.2.5 Insulin associated neurodegeneration",level:"3"},{id:"sec_28_3",title:"6.2.6 Cholinergic system in AD",level:"3"},{id:"sec_29_3",title:"6.2.7 Targeting oxidoreductases",level:"3"},{id:"sec_30_3",title:"6.2.8 Epigenetic modulations",level:"3"},{id:"sec_33",title:"7. Conclusion",level:"1"},{id:"sec_34",title:"Acknowledgments",level:"1"},{id:"sec_37",title:"Conflict of interest",level:"1"}],chapterReferences:[{id:"B1",body:'Przedborski S, Vila M, Jackson-Lewis V. Neurodegeneration: What is it and where are we? J. Clin. Invest. (2003) 111:3-10'},{id:"B2",body:'Jellinker KA. Basic mechanisms of neurodegeneration: acritical update. J Cell Mol Med. (2010) 14:457-487'},{id:"B3",body:'Hengartner MO. The biochemistry of apoptosis. Nature (2000) 407:770-776'},{id:"B4",body:'Melo A, Monteiro L, Lima RMF, de Oliveira DM, de Cerqueira MD et al. Oxidative stress in neurodegenerative diseases: mechanism and therapeutic perspectives. Oxid Med Cell Longev. (2011) 2011:467180'},{id:"B5",body:'Cassagnes L-E, Chhour M, Pério P, Sudor J, Gayon R, Ferry G, Boutin JA, Nepveu F, Reybier K. Oxidative stress and neurodegeneration: The possible contribution of quinone reductase 2. Free Rad Biol Med (2018) 120: 56-61'},{id:"B6",body:'Morroni F, Sita G, Graziosi A, Ravegnini G, Molteni R, et al. PQM130, a novel feruloyl-donepezil hybrid compound, effectively ameliorates the cognitive impairments and pathology in a mouse model of Alzheimer’s disease. Front Pharmacol. (2019) 10:658'},{id:"B7",body:'Kovacs G. Molecular pathological classification of neurodegenerative diseases: turning towards precision medicine. Int J Mol Sci. (2016) 17:189'},{id:"B8",body:'Kovacs GG, Budka H. Molecular pathology of human prion diseases. Int J Mol Sci. (2009) 10:976-999'},{id:"B9",body:'Dugger BN, Hoffman BR, Scroggins A, Serrano GE, Adler CH et Al. tau immunoreactivity in peripheral tissues of human aging and select tauopathies. Neurosci Lett. (2019) 696:132-139'},{id:"B10",body:'Desai AK, Grossberg GT. Diagnosis and treatment of Alzheimer’s disease. Neurology (2005) 64:S34–S39'},{id:"B11",body:'Chaudhuri KR, Schapira AHV. Non-motor symptoms of Parkinson’s disease: dopaminergic pathophysiology and treatment. Lancet Neurol. (2009) 8:464-474'},{id:"B12",body:'Rees K, Stowe R, Patel S, Ives N, Breen K et al. Non-steroidal anti-inflammatory drugs as disease-modifying agents for Parkinson’s disease: Evidence from observational studies. Cochrane Database Syst Rev. (2011): Cd008454'},{id:"B13",body:'Liguori I, Russo G, Curcio F, Bulli G, Aran L, et al. Oxidative stress, aging, and diseases. Clin Interv Aging. (2018) 13:757-772'},{id:"B14",body:'Nakamura T and Lipton SA. S-Nitrosylation of critical protein thiols mediates protein misfolding and mitochondrial dysfunction in neurodegenerative diseases. Antioxid Redox Sign. (2011) 14:1479-1492'},{id:"B15",body:'Cho D-H, Nakamura T, Fang J, Cieplak P, Godzik A, et al. S-Nitrosylation of Drp1 mediates beta-amyloid-related mitochondrial fission and neuronal injury. Science. (2009) 324:102-105'},{id:"B16",body:'Abtahi SL, Masoudi R, Haddadi M. The distinctive role of Tau and amyloid beta in mitochondrial dysfunction through alteration in Mfn2 and Drp1 mRNA levels: a comparative study in Drosophila melanogaster. Gene (2020) 754:144854'},{id:"B17",body:'Wang W, Zhao F, Ma X, Perry G, Zhu X. Mitochondria dysfunction in the pathogenesis of Alzheimer’s disease: recent advances. Mol Neurodegener. (2020) 15:30'},{id:"B18",body:'Harada S, Fujii C, Hayashi A, Ohkoshi N. An Association between Idiopathic Parkinson’s Disease and Polymorphisms of Phase II Detoxification Enzymes: Glutathione S-Transferase M1 and Quinone Oxidoreductase 1 and 2. Biochem Biophys Res Commun. (2001) 288: 887-892'},{id:"B19",body:'Picklo Sr MJ, Olson SJ, Markesbery WR, Montine TJ. Expression and Activities of Aldo-Keto Oxidoreductases in Alzheimer Disease. J Neuropathol Exp Neurol (2001) 60: 686-695'},{id:"B20",body:'Mota SI, Costa RO, Ferreira IL, Santana I, Caldeira GL et al. Oxidative stress involving changes in Nrf2 and ER stress in early stages of Alzheimer\'s disease. Biochim Biophys Acta. (2015) 1852:1428-1441'},{id:"B21",body:'Butterfield DA, Keller JN. Antioxidants and antioxidant treatment in disease. Biochim Biophys Acta Mol Basis Dis. (2012) 1822:615'},{id:"B22",body:'Deshmukh P, Unni S, Krishnappa G, Padmanabhan B. The Keap 1–Nrf2 pathway: promising therapeutic target to counteract ROS-mediated damage in cancers and neurodegenerative diseases. Biophys Rev. (2017) 9:41-56'},{id:"B23",body:'Rojo AI, Pajares M, Rada P, Nuñez A, Nevado-Holgado AJ, et al. NRF2 deficiency replicates transcriptomic changes in Alzheimer\'s patients and worsens APP and TAU pathology. Redox Biology. (2017) 13:444-451'},{id:"B24",body:'Carelli V, Rugolo M, Sgarbi G, Ghelli A, Zanna C, Baracca A, Lenaz G, Napoli E, Martinuzzi A, Solaini G. Bioenergetics shapes cellular death pathways in Leber’s hereditary optic neuropathy: a model of mitochondrial neurodegeneration. Biochim Biophys Acta. (2004) 1658: 172-179'},{id:"B25",body:'Adolfson R, Gottfries CG, Oreland L, Wiberg A, Winblad B. Increasedactivity of brain and platelet monoamine oxidase in dementia of Alzheimer type. Life Sci. (1980) 27: 1029-1034'},{id:"B26",body:'Banerjee S, Poddar MK. Carnosine: effect on aging-induced increase in brain regional monoamine oxidase-A activity. Neurosci Res (2015) 92: 62-70'},{id:"B27",body:'Banerjee S, Poddar MK Platelet monoamine oxidase-A activity and aging: effect of carnosine. J Physiol Sci (2013) 63:279-285'},{id:"B28",body:'Witz G. Biological interactions of α,β-unsaturated aldehydes. Free Rad Biol Med (1989) 7: 333-349'},{id:"B29",body:'Keller JN, Mark RJ, Bruce AJ, et al. 4-Hydroxynonenal, an aldehydic product of membrane lipid peroxidation, impairs glutamate transport and mitochondrial function in synaptosomes. Neurosci (1997) 80: 685-696'},{id:"B30",body:'Neely MD, Sidell KR, Graham DG, Montine TJ. The lipid peroxidation product 4-hydroxynonenal inhibits neurite outgrowth, disrupts neuronal microtubules, and modifies cellular tubulin. J Neurochem (1999) 72: 2323-2333'},{id:"B31",body:'Mitchell D, Petersen D. The oxidation of α,β unsaturated aldehydic products in lipid peroxidation by rat liver aldehyde dehydrogenases. Toxicol Appl Pharmacol (1987) 87:403-410'},{id:"B32",body:'O’Connor T, Ireland LS, Harrison DJ, Hayes JD. Major differences exist in the function and tissue-specific expression of human aflatoxin B1 aldehyde reductase and the principal human aldo-keto reductase AKR1 family members. Biochem J (1999) 343: 487-504'},{id:"B33",body:'Furuta A, Price DL, Pardo CA, et al. Localization of superoxide dismutases in Alzheimer’s disease and Down’s syndrome neocortex and hippocampus. Am J Pathol (1995) 146: 357-367'},{id:"B34",body:'Schipper HM, Cisse S, Stopa EG. Expression of heme oxygenase-1 in the senescent and Alzheimer-diseased brain. Ann Neurol (1995) 37: 758-768'},{id:"B35",body:'Burn DJ, Jaros E. Multiple system atrophy: cellular and molecular pathology. Mol. Pathol. (2001) 54:419-426'},{id:"B36",body:'Finkel SI. Effects of rivastigmine on behavioral and psychological symptoms of dementia in Alzheimer’s disease. Clin Ther (2004) 26: 980-990'},{id:"B37",body:'Okun MS, DeLong MR, Hanfelt J, Gearing M, Levey A. Plasma testosterone levels in Alzheimer and Parkinson diseases. Neurology. (2004) 62: 411-413'},{id:"B38",body:'Brooks D. Imaging studies in drug development: Parkinson’s disease. Drug Discov Today Technol. (2005a) 2:317-321'},{id:"B39",body:'Djaldetti R, Ziv I, Melamed E. The mystery of motor asymmetry in Parkinson’s disease. Lancet Neurol. (2006) 5:796-802'},{id:"B40",body:'Quinn N. Drug treatment of Parkinson’s disease. BMJ Br. Med J. (1995) 310: 575-579'},{id:"B41",body:'Strong MJ. The basic aspects of therapeutics in amyotrophic lateral sclerosis. Pharmacol Therapeut. (2003) 98: 379-414'},{id:"B42",body:'Andrews TC, Brooks DJ. Advances in the understanding of early Huntington’s disease using the functional imaging techniques of PET and SPET. Mol Med Today. (1998), 532-539'},{id:"B43",body:'Berger T, Reindl M. Multiple sclerosis: disease biomarkers as indicated by pathophysiology. J Neurol Sci. (2007) 259: 21-26'},{id:"B44",body:'Ou SH, Wu F, Harrich D, Garcia-Martinez LF, Gaynor RB. Cloning and characterization of a novel cellular protein, TDP-43, that binds to human immunodeficiency virus type 1 TAR DNA sequence motifs. J. Virol. (1995) 69:3584-3596'},{id:"B45",body:'Duyckaerts C, Delatour B, Potier MC. Classification and basic pathology of Alzheimer disease. Acta Neuropathol. (2009) 118:5-36'},{id:"B46",body:'Dehay B, Bourdenx M, Gorry P, Przedborski S, Vila M, et al. Targeting _-synuclein for treatment of Parkinson\'s disease: Mechanistic and therapeutic considerations. Lancet Neurol. (2015) 14:855-866'},{id:"B47",body:'Kovacs GG. Molecular pathology of neurodegenerative diseases: principles and practice. J Clin Pathol. (2019) 72:725-735'},{id:"B48",body:'Thal DR, Walter J, Saido TC, Fandrich M. Neuropathology and biochemistry of Aβ and its aggregates in Alzheimer’s disease. Acta Neuropathol. (2015) 129:167-182'},{id:"B49",body:'Taniguchi-Watanabe S, Arai T, Kametani F, Nonaka T, Masuda-Suzukake M, et al. Biochemical classification of tauopathies by immunoblot, protein sequence and mass spectrometric analyses of sarkosyl-insoluble and trypsin-resistant tau. Acta Neuropathol. (2016) 131:267-280'},{id:"B50",body:'Lee VM, Goedert M, Trojanowski JQ . Neurodegenerative tauopathies. Annu. Rev. Neurosci. (2001) 24:1121-1159'},{id:"B51",body:'Bertolotti A. Importance of the subcellular location of protein deposits in neurodegenerative diseases. Curr Opin Neurobiol. (2018) 51:127-133'},{id:"B52",body:'Ruz C, Alcantud JL, Vives Montero F, Duran R, Bandres-Ciga S. Proteotoxicity and Neurodegenerative Diseases. Int J Mol Sci. (2020) 21:5646'},{id:"B53",body:'Kovacs GG. Introduction: Classification of neurodegenerativediseases. In Neuropathology of Neurodegenerative Diseases: A Practical Guide. Kovacs GG, Ed; Cambridge University Press: Cambridge UK. (2015), 1-8'},{id:"B54",body:'Camprodon JA, Stern TA. Selecting neuroimaging techniques: a review for the clinician. Prim Care Companion CNS Disord. (2013) 15:PCC.12f01490'},{id:"B55",body:'Chen JJ. Functional MRI of brain physiology in aging and neurodegenerative diseases. Neuroimage. (2019) 187:209-225'},{id:"B56",body:'Malamud D. Saliva as a diagnostic fluid. Dent Clin North Am. (2011) 55:159-178'},{id:"B57",body:'Wilkins JM, Trushina E. Application of Metabolomics in Alzheimer\'s Disease. Front Neurol. (2018) 8:719'},{id:"B58",body:'García JC, Bustos RH. The Genetic Diagnosis of Neurodegenerative Diseases and Therapeutic Perspectives. Brain Sci. (2018) 8:222'},{id:"B59",body:'Seibyl J, Chen W, Silverman D. Single-photon emission computed tomography and positron emission tomography evaluations of patients with central motor disorders. Nucl Med. (2008) 03:274-286'},{id:"B60",body:'Siebner HR, Meder D, Herz DM. fMRI in Parkinson’s Disease. (2020) In: Ulmer S, Jansen O. (eds) fMRI. Springer Nature Switzerland AG'},{id:"B61",body:'Wang S, Jing H, Yang H, Liu Z, Guo H, et al. Tanshinone I selectively suppresses pro-inflammatory genes expression in activated microglia and prevents nigrostriatal dopaminergic neurodegeneration in a mouse model of Parkinson’s disease. J Ethnopharmacol. (2015) 164: 247-255'},{id:"B62",body:'Shao Y, Le W. Recent advances and perspectives of metabolomics-based investigations in Parkinson’s disease. Mol Neurodegeneration. (2019) 14:3'},{id:"B63",body:'Honson NS, Johnson RL, Huang W, Inglese J, Austin CP, et al. Differentiating Alzheimer disease-associated aggregates with small molecules. Neurobiol Dis. (2007) 28: 251-260'},{id:"B64",body:'Small GW, Bookheimer S, Thompson PM. Current and future uses of neuroimaging for cognitively impaired patients. Lancet Neurol. (2008) 7:161-172'},{id:"B65",body:'Craig-Schapiro R, Fagan AM, Holtzman DM. Biomarkers of Alzheimer\'sdisease. Neurobiol Dis. (2009) 35:128-140'},{id:"B66",body:'Petrella J, Coleman E, Doraiswamy P. Neuroimaging and early diagnosis of Alzheimer disease: a look to the future. Radiology. (2003) 226:315-336'},{id:"B67",body:'Jagust W. Molecular neuroimaging in Alzheimer’s disease. NeuroRx. (2004) 1: 206-212'},{id:"B68",body:'Schipper HM. The role of biologic markers in the diagnosis of Alzheimer’s disease. Alzheimers Dement. (2007) 3:325-332'},{id:"B69",body:'Hampel H, Goernitz A, Buerger K. Advances in the development of biomarkers for Alzheimer’s disease: from CSF total tau and A 1-42 proteins to phosphorylated tau protein. Brain Res Bull. (2003) 61:243-253'},{id:"B70",body:'Waragai M, Okamura N, Furukawa N, Tashiro M, Furumoto S et al. Comparison study of amyloid PET and voxel-based morphometry analysis in mild cognitive impairment and Alzheimer’s disease. J Neurol Sci. (2009) 285:100-108'},{id:"B71",body:'Cai L. Synthesis and evaluation of two 18F-Labeled 6-Iodo-2-(4c-N,N dimethylamino) phenylimidazo [1,2-a]pyridine derivatives as prospective radioligands for a-amyloid in Alzheimer’s disease. J Med Chem. (2004) 4: 2208-2218'},{id:"B72",body:'Kulkarni PV, Arora V, Roney AC, White C, Bennett M et al. Radiolabeled probes for imaging Alzheimer’s plaques. Nucl Instrum B. (2005) 241: 676-680'},{id:"B73",body:'Kloppel S, Henley SM, Hobbs NZ, Wolf RC, Kassubek J, et al. Magnetic resonance imaging of Huntington’s disease: preparing for clinical trials. Neuroscience. (2009) 164: 205-219'},{id:"B74",body:'Paulsen JS. Functional imaging in Huntington’s disease. Exp Neurol. (2009) 216: 272-277'},{id:"B75",body:'Wong FC, Kim EE. A review of molecular imaging studies reaching the clinical stage. Eur J Radiol. (2009) 70: 205-211'},{id:"B76",body:'Tai YF, Pavese N, Gerhard A, Tabrizi SJ, Barker RA, et al. Imaging microglial activation in Huntington’s disease. Brain Res Bull. (2007) 72:148-151'},{id:"B77",body:'Mastrokolias A, Pool R, Mina E, Hettne KM, van Duijn E et al. Integration of targeted metabolomics and transcriptomics identifies deregulation of phosphatidylcholine metabolism in Huntington\'s disease peripheral blood samples. Metabolomics. (2016) 12:137'},{id:"B78",body:'Lloyd CM, Richardson MP, Brooks DJ, Al-Chalabi A, Leigh PN. Extramotor involvement in ALS: PET studies with GABAA ligand [11C] flumazenil. Brain (2000) 123: 2298-2296'},{id:"B79",body:'Turner NR, Cagnin A, Turkheimer FE, Miller CCJ, Shaw CE, et al. Evidence of widespread cerebral microglial activation in amyotrophic lateral sclerosis: an [11C] (R)-PK11195 positron emission tomography study. Neurobiol Dis. (2004) 15: 601-609'},{id:"B80",body:'Karitzky J, Ludolph AC. Imaging and neurochemical markers for diagnosis and disease progression in ALS. J Neurol Sci. (2001) 191:35-41'},{id:"B81",body:'Vogels OMJ, Veltman J, Oyen WJG, Horstink MWI. Decreased striatal dopamine D2 receptor binding in amyotrophic lateral sclerosis (ALS) and multiple system atrophy (MSA): D2 receptor down-regulation versus striatal cell degeneration. J Neurol Sci. (2000) 180: 62-65'},{id:"B82",body:'Petri S, Kollewe K, Grothe C, Hori A, Dengler R, et al. GABAA-receptor mRNA expression in the prefrontal and temporal cortex of ALS patients. J Neurol Sci. (2006) 250: 124-132'},{id:"B83",body:'Tumani H, Hartung H-P, Hemmer B, Teunissen C, Deisenhammer F, et al. Cerebrospinal fluid biomarkers in multiple sclerosis. Neurobiol Dis. (2009) 35: 117-127'},{id:"B84",body:'Pustovrh I, Predić P, Hrastnik D, Gregorić E. Tc-99m-MIBI brain SPECT in diagnosis of multiple sclerosis acute phase. J Neurol Sci. (1997):(Slupp 1):S329'},{id:"B85",body:'Bakshi R, Minagar A, Jaisani Z, Wolinsky JS. Imaging of multiple sclerosis: role in neurotherapeutics. NeuroRx_. Journal of the American Society for Experimental NeuroTherapeutics. (2005) 2: 277-303'},{id:"B86",body:'Filippi M, Rocca MA. Present and future of fMRI in multiple sclerosis. Expert Rev Neurother. (2013) 13:27-31'},{id:"B87",body:'Mangalam A, Poisson L, Nemutlu E, Datta I, Denic A, et al. Profile of circulatory metabolites in a relapsing-remitting animal model of multiple sclerosis using global metabolomics. J Clin Cell Immunol (2013) 4. 10.4172/2155-9899.1000150'},{id:"B88",body:'Apostolova LG, Steiner CA, Akopyan GG, Dutton RA, Hayashi KM, et al. Three-dimensional gray matter atrophy mapping in mild cognitive impairment and mild Alzheimer disease. Arch Neurol. (2007) 64:1489-1495'},{id:"B89",body:'Thompson PM, Woods RP, Mega MS, Toga AW. Mathematical/computational challenges in creating deformable and probabilistic atlases of the human brain. Hum Brain Mapp. (2000) 9:81-92'},{id:"B90",body:'Brodmann K. On the comparative localization of the cortex. Springfield, IL: Thomas; 1960. Translated from Brodman, K. Vergleichende Lokalizationslehre der Grosshirnrinde in ihren Prinzipien dargestellt auf Grund des Zellenbaues, 1909, Barth, Leipzig'},{id:"B91",body:'Yushkevich PA, Piven J, Hazlett HC, Smith RG, Ho S et al. User-guided 3D active contour segmentation of anatomical structures: significantly improved efficiency and reliability. Neuroimage. (2006) 31:1116-1128'},{id:"B92",body:'Pitiot A, Delingette H, Thompson PM, Ayache N. Expert knowledge-guided segmentation system for brain MRI. Neuroimage. (2004) 23:S85–S96'},{id:"B93",body:'Hogan RE, Mark KE, Wang L, Joshi S, Miller MI et al. Mesial temporal sclerosis and temporal lobe epilepsy: MR imaging deformation-based segmentation of the hippocampus in five patients. Radiology. (2000) 216:291-297'},{id:"B94",body:'Ashburner J, Friston KJ. Why voxel-based morphometry should be used. Neuroimage. (2001) 14:1238-1243'},{id:"B95",body:'Friston KJ, Holmes AP, Worsley KJ, Poline J-P, Frith CD, et al. Statistical parametric maps in functional imaging: a general linear approach. Hum Brain Mapp. (1995) 2:189-210'},{id:"B96",body:'Good CD, Johnsrude IS, Ashburner J, Henson RN, Friston KJ et al. A voxel-based morphometric study of ageing in 465 normal adult human brains. Neuroimage. (2001) 14:21-36'},{id:"B97",body:'Busatto GF, Garrido GE, Almeida OP, Castro CC, Camargo CHP, et al. A voxel-based morphometry study of temporal lobe gray matter reductions in Alzheimer’s disease. Neurobiol Aging. (2003) 24: 221-231'},{id:"B98",body:'Mummery CJ, Patterson K, Price CJ, Ashburner J, Frackowiak RS et al. A voxel-based morphometry study of semantic dementia: relationship between temporal lobe atrophy and semantic memory. Ann Neurol. (2000) 47:36-45'},{id:"B99",body:'Gitelman DR, Ashburner J, Friston KJ, Tyler LK, Price CJ et al. Voxel-based morphometry of herpes simplex encephalitis. Neuroimage. (2001) 13:623-631'},{id:"B100",body:'Whitwell JL, Weigand SD, Shiung MM, Boeve BF, Ferman TJ, et al. Focal atrophy in dementia with Lewy bodies on MRI: a distinct pattern from Alzheimer’s disease. Brain. (2007) 130:708-719'},{id:"B101",body:'Salmond CH, Ashburner J, Vargha-Khadem F, Connelly A, Gadian DG et al. Distributional assumptions in voxel-based morphometry. Neuroimage. (2002) 17:1027-1030'},{id:"B102",body:'Gee JC, Thompson PM. Guest editorial: Special issue on computational neuroanatomy. IEEE Trans Med Imaging. (2007) 26:425-426'},{id:"B103",body:'Chiang MC, Dutton RA, Hayashi KM, Lopez OL, Aizenstein HJ, et al. 3D pattern of brain atrophy in HIV/AIDS visualized using tensor-based morphometry. Neuroimage. (2007) 34:44-60'},{id:"B104",body:'Thompson PM, Hayashi KM, de Zubicaray G, Janke AL, Rose SE, et al. Dynamics of gray matter loss in Alzheimer’s disease. J Neurosci. (2003) 23:994-1005'},{id:"B105",body:'Frisoni GB, Pievani M, Testa C, Sabattoli F, Bresciani L, et al. The topography of grey matter involvement in early and late onset Alzheimer’s disease. Brain. (2007)130:720-730'},{id:"B106",body:'Bookheimer SY, Braskie MN, Burggren AC., et al. Functional MRI and structure-function mapping in the early diagnosis of Alzheimer’s disease. Annual Meeting of the Americal College of Neuropsychopharmacology; Hollywood, FL. 2006'},{id:"B107",body:'Ballmaier M, O’Brien JT, Burton EJ, Thompson PM, Rex DE, et al. Comparing gray matter loss profiles between dementia with Lewy bodies and Alzheimer’s disease using cortical pattern matching: diagnosis and gender effects. Neuroimage. (2004) 23:325-335'},{id:"B108",body:'Bäckman L, Jones S, Berger AK, Laukka EJ, Small BJ. Cognitive impairment in preclinical Alzheimer\'s disease: a meta-analysis. Neuropsychology. (2005)19:520-531'},{id:"B109",body:'Agarwal R, Chhillar N, Kushwaha S, Singh NK, Tripathi CB. Role of vitamin B(12), folate, and thyroid stimulating hormone in dementia: A hospital-based study in north Indian population. Ann Indian Acad Neurol. (2010) 13:257-262'},{id:"B110",body:'Price BR, Wilcock DM, Weekman EM. Hyperhomocysteinemia as a Risk Factor for Vascular Contributions to Cognitive Impairment and Dementia. Front Aging Neurosci. (2018) 10:350'},{id:"B111",body:'Barnes DE, Alexopoulos GS, Lopez OL, Williamson JD, Yaffe K. Depressive symptoms, vascular disease, and mild cognitive impairment: findings from the Cardiovascular Health Study. Arch. Gen. Psychiatry. (2006) 63: 273-279'},{id:"B112",body:'Monastero R, Palmer K, Qiu C, Winblad B, Fratiglioni L. Heterogeneity in risk factors for cognitive impairment, no dementia: population-based longitudinal study from the Kungsholmen Project. Am J Geriatr Psychiatry. (2007) 15: 60-69'},{id:"B113",body:'Qiu C, Kivipelto M, von Strauss E. Epidemiology of Alzheimer\'s disease: occurrence, determinants, and strategies toward intervention. Dialogues Clin Neurosci. (2009) 11:111-128'},{id:"B114",body:'Poddar MK, Banerjee S, Chakraborty A, Dutta D.Metabolic disorder in Alzheimer’s disease. Metab Brain Dis. Communicated. (2020)'},{id:"B115",body:'Gatz M, Reynolds CA, Fratiglioni L, Johansson B, Mortimer JA, et al. Role of genes and environments for explaining Alzheimer disease. Arch. Gen. Psychiatry. (2006) 63:168-174'},{id:"B116",body:'Fratiglioni L, von Strauss E, Qiu C. Epidemiology of the dementias of old age. In: Jacoby R, Oppenheimer C, Dening T, Thomas A. (Eds.), The Oxford Textbook of Old Age Psychiatry. Oxford University Press, New York, (2008): 391-406'},{id:"B117",body:'Bertram L, Tanzi RE. The genetic epidemiology of neurodegenerative disease. J. Clin. Invest. (2005) 115: 1449-1457'},{id:"B118",body:'Xu W, Qiu C, Winblad B, Fratiglioni L. The effect of borderline diabetes on the risk of dementia and Alzheimer’s disease. Diabetes. (2007), 56:211-216'},{id:"B119",body:'Kröger E, Andel R, Lindsay J, Benounissa Z, Verreault R, et al. Is complexity of work associated with risk of dementia? The canadian study of health and aging. Am. J. Epidemiol. (2008) 167:820-830'},{id:"B120",body:'Alzheimer’s disease facts and figures. Alzheimer’s Dement. (2020) 16:391-460'},{id:"B121",body:'Palmer S, RD. Smart Eating— How Diet May Help Preserve the Brain. (2009) 11(7):24'},{id:"B122",body:'Valenzuela R, Valenzuela B. Docosahexaenoic Acid (DHA), in the Prevention and Treatment of Neurodegenerative Diseases. Neurodegenerative Diseases - Processes, Prevention, Protection and Monitoring, Raymond Chuen-Chung Chang, IntechOpen. (2011) 10.5772/28000'},{id:"B123",body:'Siddiqui R, Harvey K, Bammerlin E, Ikhlaque N. Docosahexaenoic Acid: A Potential Modulator of Brain Tumors and Metastasis. J. Biomol. Res. Ther. (2013) 2:10.4172/2167-7956.1000e119'},{id:"B124",body:'Gomez-Pinilla F, Nguyen TT. Natural mood foods: the actions of polyphenols against psychiatric and cognitive disorders. Nutr Neurosci. (2012) 15:127-133'},{id:"B125",body:'Di Meo F, Margarucci S, Galderisi U, Crispi S, Peluso G. Curcumin, Gut Microbiota, and Neuroprotection. Nutrients. (2019) 11:2426'},{id:"B126",body:'Bourre JM. Effects of nutrients (in food) on the structure and function of the nervous system: update on dietary requirements for brain. Part 1: micronutrients. J Nut Health Aging (2006) 10:377-385'},{id:"B127",body:'Luchsinger JA, Tang MX, Miller J, Green R, Mayeux R. Relation of higher folate intake to lower risk of Alzheimer disease in the elderly. Arch Neurol. (2007) 64:86-92'},{id:"B128",body:'Gu Y, Schupf N, Cosentino SA, Luchsinger JA, Scarmeas N. Nutrient intake and plasma β-amyloid. Neurology. (2012) 78:1832-1840'},{id:"B129",body:'Fratiglioni L, Winblad B, von Strauss E. Prevention of Alzheimer\'s disease and dementia. Major findings from the Kungsholmen Project. Physiol Behav. (2007) 92:98-104'},{id:"B130",body:'Berti V, Murray J, Davies M, Spector N, Tsui WH, et al. Nutrient patterns and brain biomarkers of Alzheimer’s disease in cognitively normal individuals. J Nutr Health Aging. (2015) 19:413-423'},{id:"B131",body:'Chakraborty A, Banerjee S, Mukherjee B, Poddar MK. Calorie restriction improves aging-induced impairment of cognitive function in relation to deregulation of brain regional GABA system and corticosterone status. Mech Ageing Dev (2020) 189: 111242. 248'},{id:"B132",body:'Zhang Y, Liu C, Zhao Y, Zhang X, Li B, et al. The Effects of Calorie Restriction in Depression and Potential Mechanisms. Curr Neuropharmacol. (2015) 13:536-542'},{id:"B133",body:'Ashrafian H, Harling L, Darzi A, Athanasiou T. Neurodegenerative disease and obesity: what is the role of weight loss and bariatric interventions? Metab Brain Dis. (2013) 28:341-353'},{id:"B134",body:'Dudar JD, Whishaw IQ , Szerb JC. Release of acetylcholine from the hippocampus of freely moving rats during sensory stimulation and running. Neuropharmacology. (1979) 18:673-678'},{id:"B135",body:'Maass A, Duzel S, Brigadski T, Goerke M, Becke A, et al. Relationships of peripheral IGF-1, VEGF and BDNF levels to exercise-related changes in memory, hippocampal perfusion and volumes in older adults. NeuroImage. (2016) 131:142-154'},{id:"B136",body:'Sleiman SF, Henry J, Al-Haddad R, El Hayek L, Abou Haidar E, et al. Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body beta-hydroxybutyrate. Elife. (2016) 5:e15092'},{id:"B137",body:'Ieraci A, Madaio AI, Mallei A, Lee FS, Popoli M. Brain-derived neurotrophic factor Val66Met human polymorphism impairs the beneficial exercise-induced neurobiological changes in mice. Neuropsychopharmacology. (2016) 41:3070-3079'},{id:"B138",body:'Wrann CD, White JP, Salogiannnis J, Laznik-Bogoslavski D, Wu J, et al. Exercise induces hippocampal BDNF through a PGC-1alpha/FNDC5 pathway. Cell Metab. (2013) 18:649-659'},{id:"B139",body:'Allard JS, Ntekim O, Johnson SP, Ngwa JS, Bond V, et al. APOEε4 impacts up-regulation of brain-derived neurotrophic factor after a six-month stretch and aerobic exercise intervention in mild cognitively impaired elderly African Americans: A pilot study. Exp Gerontol. (2017) 87:129-136'},{id:"B140",body:'Khorshid AT, Acosta C, Cortes C, Lakowski T, Gangadaran S, et al. Transcriptional regulation of brain-derived neurotrophic factor (BDNF) by methyl CpG binding protein 2 (MeCP2): a novel mechanism for re-myelination and/or myelin repair involved in the treatment of multiple sclerosis (MS). Mol Neurobiol. (2016) 53:1092-1107'},{id:"B141",body:'Gao Y, Zhao Y, Pan J, Yang L, Huang T, et al. Treadmill exercise promotes angiogenesis in the ischemic penumbra of rat brains through caveolin-1/VEGF signaling pathways. Brain Res. (2014) 1585:83-90'},{id:"B142",body:'Rich B, Scadeng M, Yamaguchi M, Wagner PD, Breen EC. Skeletal myofiber vascular endothelial growth factor is required for the exercise training-induced increase in dentate gyrus neuronal precursor cells. J Physiol. (2017) 595:5931-5943'},{id:"B143",body:'Cotman CW, Berchtold NC, Christie LA. Exercise builds brain health: key roles of growth factor cascades and inflammation. Trends Neurosci. (2007) 30:464-472'},{id:"B144",body:'Knochel C, Oertel-Knochel V, O’Dwyer L, Prvulovic D, Alves G, et al. Cognitive and behavioural effects of physical exercise in psychiatric patients. Prog Neurobiol. (2012) 96:46-68'},{id:"B145",body:'Zimmer P, Stritt C, Bloch W, Schmidt FP, Hubner ST, et al. The effects of different aerobic exercise intensities on serum serotonin concentrations and their association with Stroop task performance: a randomized controlled trial. Eur J Appl Physiol. (2016) 116:2025-2034'},{id:"B146",body:'Audhya T, Adams JB, Johansen L. Correlation of serotonin levels in CSF, platelets, plasma, and urine. Biochim Biophys Acta. (2012) 1820:1496-1501'},{id:"B147",body:'Law LL, Rol RN, Schultz SA, Dougherty RJ, Edwards DF, et al. Moderate intensity physical activity associates with CSF biomarkers in a cohort at risk for Alzheimer’s disease. Alzheimers Dement (Amst). (2018) 10:188-195'},{id:"B148",body:'Schenkman M, Moore CG, Kohrt WM, Hall DA, Delitto A, et al. Effect of high-intensity treadmill exercise on motor symptoms in patients with de novo Parkinson Disease: a phase 2 randomized clinical trial. JAMA Neurol. (2018) 75:219-226'},{id:"B149",body:'Shin MS, Kim TW, Lee JM, Ji ES, Lim BV. Treadmill exercise alleviates nigrostriatal dopaminergic loss of neurons and fibers in rotenone-induced Parkinson rats. J Exerc Rehabil. (2017) 13:30-35'},{id:"B150",body:'Shaw LM, Korecka M, Clark CM, Lee V M-Y, Trojanowski JQ . Biomarkers of neurodegeneration for diagnosis and monitoring therapeutics. Nat Rev Drug Discov. (2007) 6:295-303'},{id:"B151",body:'Tomita T, Iwatsubo T. The inhibition of gamma-secretase as a therapeutic approach to Alzheimer\'s disease. Drug News Perspect. (2004)17:321-325'},{id:"B152",body:'Arosio P, Vendruscolo M, Dobson CM, Knowles TP. Chemical kinetics for drug discovery to combat protein aggregation diseases. Trends Pharmacol Sci. (2014) 35:127-135'},{id:"B153",body:'Lee JH, Jeong SK, Kim B, Park K, Dash A. Donepezil across the spectrum of Alzheimer’s disease: Dose optimization and clinical relevance. Acta Neurol Scand. (2015) 131:259-267'},{id:"B154",body:'Bonuccelli U, Colzi A, Del Dotto P. Pergolide in the treatment of patients with early and advanced Parkinson’s disease. Clin. Neuropharmacol. (2002) 25:1-10'},{id:"B155",body:'McMurray CT. Huntington’s disease: New hope for therapeutics. Trends Neurosci. (2001) 24: S32–S38'},{id:"B156",body:'Faissner S, Gold R. Oral therapies for multiple sclerosis. Cold Spring Harb. Perspect. Med. (2019) 9:a032011'},{id:"B157",body:'Hussain R, Zubair H, Pursell S, Shahab M Neurodegenerative Diseases: Regenerative Mechanisms and Novel Therapeutic Approaches. Brain Sciences. 2018 Sep;8(9). DOI: 10.3390/brainsci8090177'},{id:"B158",body:'Chaturvedi SK, Alam P, Khan JM, Siddiqui MK, Kalaiarasan P, et al. Biophysical insight into the anti-amyloidogenic behavior of taurine. Int J Boil Macromol. (2015) 80: 375-384'},{id:"B159",body:'Hartl FU. Protein misfolding diseases. Annu Rev Biochem. (2017) 86: 21-26'},{id:"B160",body:'Jackrel ME, Shorter J. Engineering enhanced protein disaggregases for neurodegenerative disease. Prion. (2015) 9: 90-109'},{id:"B161",body:'Patterson KR, Ward SM, Combs B, Voss K, Kanaan NM et al. Heat shock protein 70 prevents both tau aggregation and the inhibitory effects of preexisting tau aggregates on fast axonal transport. Biochemistry. (2011) 50: 10300-10310'},{id:"B162",body:'Evans CG, Wisén S, Gestwicki JE. Heat shock proteins 70 and 90 inhibit early stages of amyloid beta (1-42) aggregation in vitro. J Boil Chem (2006) 281(44):33182-33191'},{id:"B163",body:'Maiti P, Manna J, Veleri S, Frautschy S. Molecular chaperone dysfunction in neurodegenerative diseases and effects of curcumin. BioMed Res Int. (2014) 2014: 495091'},{id:"B164",body:'Dedmon MM, Christodoulou J, Wilson MR, Dobson CM. Heat shock protein 70 inhibits alpha-synuclein fibril formation via preferential binding to prefibrillar species. J Boil Chem (2005) 280: 14733-14740'},{id:"B165",body:'Ciechanover A, Kwon YT. Protein quality control by molecular chaperones in neurodegeneration. Front. Neurosci. (2017) 11:185'},{id:"B166",body:'Björkqvist M, Wild EJ, Thiele J, Silvestroni A, Andre R, et al. A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington’s disease. J. Exp. Med. (2008) 205:1869-1877'},{id:"B167",body:'Miron VE, Boyd A, Zhao JW, Yuen TJ, Ruckh JM et al. M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination. Nat. Neurosci. (2013) 16: 1211-1218'},{id:"B168",body:'Träger U, Andre R, Lahiri N, Magnusson-Lind A, Weiss A, et al. HTT-lowering reverses Huntington’s disease immune dysfunction caused by NF_B pathway dysregulation. Brain J Neurol. (2014) 137:819-833'},{id:"B169",body:'Brochard V, Combadiere B, Prigent A, Laouar Y, Perrin A, et al. Infiltration of CD4+ lymphocytes into the brain contributes to neurodegeneration in a mouse model of Parkinson disease. J Clin Investig. (2009) 119:182-192'},{id:"B170",body:'Games D, Valera E, Spencer B, Rockenstein E, Mante M, et al. Reducing C-terminal-truncated alpha-synuclein by immunotherapy attenuates neurodegeneration and propagation in Parkinson’s disease-like models. J. Neurosci. (2014) 34: 9441-9454'},{id:"B171",body:'Boland B, Kumar A, Lee S, Platt FM, Wegiel J, et al. Autophagy induction and autophagosome clearance in neurons: Relationship to autophagic pathology in Alzheimer’s disease. J Neurosci. (2008) 28: 6926-6937'},{id:"B172",body:'Nixon RA. The role of autophagy in neurodegenerative disease. Nat Med. (2013) 19: 983-997'},{id:"B173",body:'Pupyshev AB, Korolenko TA, Tikhonova MA. A therapeutic target for inhibition of neurodegeneration: Autophagy. Neurosci Behav Physiol. (2017) 47:1109-1127'},{id:"B174",body:'Hara T, Nakamura K, Matsui M, Yamamoto A, Nakahara Y, et al. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature. (2006) 441: 885-889'},{id:"B175",body:'Liang C-C, Wang C, Peng X, Gan B, Guan J-L. Neural-specific deletion of FIP200 leads to cerebellar degeneration caused by increased neuronal death and axon degeneration. J Boil Chem. (2010) 285: 3499-3509'},{id:"B176",body:'Choi SJ, Panhelainen A, Schmitz Y, Larsen KE, Kanter E, et al. Changes in neuronal dopamine homeostasis following 1-methyl-4-phenylpyridinium (MPP+) exposure. J Boil Chem. (2015) 290: 6799-6809'},{id:"B177",body:'Steele JW, Gandy S. Latrepirdine (Dimebon®), a potential alzheimer therapeutic, regulates autophagy and neuropathology in an Alzheimer mouse model. Autophagy. (2013) 9: 617-618'},{id:"B178",body:'Berger Z, Ravikumar B, Menzies FM, Oroz LG, Underwood BR, et al. Rapamycin alleviates toxicity of different aggregate-prone proteins. Hum Mol Genet. (2005) 15: 433-442'},{id:"B179",body:'Sun Q , Wei L-L, Zhang M, Li T-X, Yang C, et al. Rapamycin inhibits activation of ampk-mTOR signaling pathway-induced Alzheimer’s disease lesion in hippocampus of rats with type 2 diabetes mellitus. Int J Neurosci. (2018) 2018:1-22'},{id:"B180",body:'Allen SJ, Watson JJ, Dawbarn D. The neurotrophins and their role in Alzheimer’s disease. Curr Neuropharmacol. (2011) 9:559-573'},{id:"B181",body:'Jiao SS, Shen LL, Zhu C, Bu XL, Liu YH, et al. Brain-derived neurotrophic factor protects against tau-related neurodegeneration of Alzheimer’s disease. Transl Psychiatry. (2016) 6: e907'},{id:"B182",body:'Middlemas DS, Kihl BK, Zhou J, Zhu X. Brain-derived neurotrophic factor promotes survival and chemoprotection of human neuroblastoma cells. J Boil Chem. (1999) 274: 16451-16460'},{id:"B183",body:'Weissmiller AM, Wu C. Current advances in using neurotrophic factors to treat neurodegenerative disorders. Transl Neurodegener. (2012) 1:14'},{id:"B184",body:'Costa A, Peppe A, Carlesimo GA, Zabberoni S, Scalici F, et al. Brain-derived neurotrophic factor serum levels correlate with cognitive performance in Parkinson’s disease patients with mild cognitive impairment. Front Behav Neurosci. (2015) 9:253'},{id:"B185",body:'Pan W, Banks WA, Kastin AJ. Permeability of the blood–brain barrier to neurotrophins. Brain Res. (1998) 788: 87-94'},{id:"B186",body:'Markianos M, Panas M, Kalfakis N, Vassilopoulos D. Plasma testosterone in male patients with Huntington’s disease: Relations to severity of illness and dementia. Ann Neurol. (2005) 57:520-525'},{id:"B187",body:'Bove R, Musallam A, Healy BC, Raghavan K, Glanz BI, et al. Low testosterone is associated with disability in men with multiple sclerosis. Mult Scler. (2014) 20:1584-1592'},{id:"B188",body:'Dye RV, Miller KJ, Singer EJ, Levine AJ. Hormone replacement therapy and risk for neurodegenerative diseases. Int J Alzheimers Dis. (2012) 2012:258454'},{id:"B189",body:'Blázquez E, Velázquez E, Hurtado-Carneiro V, Ruiz-Albusac JM. Insulin in the brain: Its pathophysiological implications for states related with central insulin resistance, type 2 diabetes and Alzheimer’s disease. Front Endocrinol. (2014) 5:161'},{id:"B190",body:'Talbot K, Wang H-Y, Kazi H, Han L-Y, Bakshi KP, et al. Demonstrated brain insulin resistance in Alzheimer’s disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline. J Clin Investig. (2012) 122:1316-1338'},{id:"B191",body:'Kang H, Khang R, Ham S, Jeong GR, Kim H, et al. Activation of the ATF2/CREB-PGC-1_ pathway by metformin leads to dopaminergic neuroprotection. Oncotarget. (2017) 8:48603-48618'},{id:"B192",body:'Bowen DM, Smith CB, White P, Davison AN. Neurotransmitter-related enzymes and indices of hypoxia in senile dementia and other abiotrophies. Brain J Neurol. (1976) 99: 459-496'},{id:"B193",body:'Whitehouse PJ, Price DL, Clark AW, Coyle JT, DeLong MR. Alzheimer disease: Evidence for selective loss of cholinergic neurons in the nucleus basalis. Ann Neurol Off J Am Neurol Assoc Child Neurol Soc. (1981) 10:122-126'},{id:"B194",body:'Drachman DA, Leavitt J. Human memory and the cholinergic system: A relationship to aging? Arch Neurol. (1974) 30:113-121'},{id:"B195",body:'Massoud F, Gauthier S. Update on the pharmacological treatment of Alzheimer’s disease. Curr Neuropharmacol. (2010) 8:69-80'},{id:"B196",body:'Barua S, Kim JY, Yenari MA, Lee JE. The role of NOX inhibitors in neurodegenerative diseases. IBRO Reports (2019) 7: 59-69'},{id:"B197",body:'Pal R, Cristan EA, Schnittker K, Narayqn M. Rescue of ER oxidoreductase function through polyphenolic phytochemical intervention: Implications for subcellular traffic and neurodegenerative disorders. Biochem Biophys Res Commun (2010) 392: 567-571'},{id:"B198",body:'Gopinath K, Sudhandiran G. Naringin modulates oxidative stress and inflammation in 3-nitropropionic acid-induced neurodegeneration through the activation of nuclear factor-erythroid-2-related factor-2 signalling pathway. Neurosci (2012) 227: 134-143'},{id:"B199",body:'Banerjee S. Aging-induced neurodegeneration in relation to brain regional A-beta deposition, locomotor and cognitive function: role of carnosine. J Neurochem (2019) 150: 125'},{id:"B200",body:'Banerjee S, Mukherjee B, Poddar MK. Carnosine restores aging-induced elevation of corticosterone status and brain regional amyloid-beta in relation to down regulation of locomotor activity. J Syst Integr Neurosci (2019) 5: 1-11'},{id:"B201",body:'Karim MF, Banerjee S, Poddar MK. Does patchouli oil change blood platelet monoamine oxidase-A activity of adult mammals? J Physiol Sci (2018) 68: 281-291'},{id:"B202",body:'Kilgore M, Miller CA, Fass DM, Hennig KM, Haggarty SJ, et al. Inhibitors of class 1 histone deacetylases reverse contextual memory deficits in a mouse model of Alzheimer’s disease. Neuropsychopharmacology. (2010) 35(4):870-880'},{id:"B203",body:'Jowaed A, Schmitt I, Kaut O, Wullner U. Methylation regulates alpha-synuclein expression and is decreased in Parkinson’s disease patients’ brains. J Neurosci. (2010) 30:6355-6359'},{id:"B204",body:'Outeiro TF, Kontopoulos E, Altmann SM, Kufareva I, Strathearn KE, et al. Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson’s disease. Science. (2007) 317:516-519'},{id:"B205",body:'Nicholas AP, Lubin FD, Hallett PJ, Vattem P, Ravenscroft P, et al. Striatal histone modifications in models of levodopa-induced dyskinesia. J Neurochem. (2008) 106:486-494'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Mrinal K. Poddar",address:"mrinalkp@yahoo.com",affiliation:'
Department of Pharmaceutical Technology, Jadavpur University, India
Department of Psychology, Neuroscience Program, Central Michigan University, USA
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1. Introduction
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In 1994, when computers had just begun to be accessible to regular classrooms, an article titled “Why Use Technology?” was published [1]. The authors, Kyle Peck and Denise Dorricott, began the article by asking the question “If we removed all of the computers from schools tomorrow, would it make a big difference in the knowledge and skills students demonstrated upon graduation?” They answered, “Probably not.” In the minds of Peck and Dorricott, the introduction of computers in K-12 schools did not create an electronic highway of accelerated learning but rather a dirt road without clear expectations or purpose. More than two decades have passed, and in that time, technological progress has surpassed anyone’s imagination. Technologies are more capable, diverse, and accessible than ever. However, if we ask the same question again, we believe the answer is still no. This is probably because the pace of school reform is far behind the pace of digital progress. The techniques and tools that are used by today’s teachers to achieve learning goals are not fundamentally different from the ones used in previous decades [2]. Teachers use Google Docs to replace printed worksheets and documents, use videos and PowerPoints to replace handwriting and drawing on backboards, use text messages as an alternative to traditional communications, and use digital student records instead of hard copies. Based on a 2017 report on a national survey, the aforementioned uses of technologies have comprised the most popular educational technologies in the US K-12 education [3]. Other more creative uses of technologies—such as guiding students to do digital investigations, creating videos of lessons, and making a class blog to enhance discussion—are much less popular among teachers (see Figure 1) [3]. Apparently, technologies have not fundamentally changed the activities of teaching and learning; neither have they brought much innovation into classrooms. It is true that technologies have been well integrated into science and engineering majors in higher education and now effectively help adults to fulfill self-learning through online courses on Coursera or EdX, for example. But somehow there is a decade-long struggle surrounding technology adoption in K-12 education. In order to make a breakthrough, we will take an in-depth look into current technologies that have been used in the education context and attempt to categorize them in relation to pedagogical practices. Thereafter, we will study factors that affect the use of technologies in different categories as well as explore the following questions: Can technology replace teachers? How can we take full advantage of the power of technology to improve teaching and learning in the age of digitalization and artificial intelligence?
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Figure 1.
Percentage of K-12 teachers engaged in the use of technologies in the USA. Note: Data source from Project Tomorrow’s 2017 Report [3].
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2. Categorization of educational technologies
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Digital technologies are very diverse—different technologies have unique functions and features that are distinct from one another, and hence, generalization should be avoided when studying the use of technology in any field. Unfortunately, most current studies on technology in the field of education regard them as a singular concept without making any distinctions among different kinds of technologies—as if all technologies are homogeneous. To correct this widespread and long-lasting oversight, we will attempt to categorize technologies that have been employed in educational settings.
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2.1 Pedagogical technologies vs. operational technologies
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Educational technologies can be categorized into two groups: pedagogical technologies and operational technologies. The first category refers to technologies that can be utilized in the process of teaching and learning. For example, teachers use PowerPoint presentations to deliver effective instruction, and students use the Internet to conduct independent research. Those technologies in the aforementioned uses are pedagogical technologies. The second category refers to technologies that are not directly involved in learning and teaching activities; instead, they assist in the operative or administrative part of teachers’ work, such as using email to communicate with colleagues and using an online data management system to keep student records. Those two categories are not completely distinct from each other. They could have some slight overlaps. For example, teachers can use some online learning management platforms to both keep assignment grades and simultaneously deliver feedback to students. Technologies are also interchangeable between the two groups—when Word is used to produce learning materials, it is a pedagogical technology, and when used to write work reports, it is an operational technology. The human use of technologies defines their essence. This categorization should only be considered in relation to a specific technology or a technological element under a specific use. It is hard to say which category of technologies is more popular in educational settings. It is also difficult to demonstrate which ones have a greater impact on teachers’ daily work. But, for the purpose of this chapter, we only focus on technologies that directly influence teaching and learning—pedagogical technologies.
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2.2 Tool-based technologies vs. program-based technologies
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The process and resources needed for teachers to adopt technologies are qualitatively different across different kinds of technologies [4]. Countless individual technologies can be employed in pedagogical practices, and pedagogical technologies can be further categorized into two large groups: tool-based technologies and program-based technologies.
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Tool-based technologies are the ones not specifically designed for education. They are merely tools that have been widely used in various fields, such as the Internet, Smartboards, and Microsoft Office, among others. Most technologies that have been widely used and studied in educational settings belong to this category. They came into education decades ago as society underwent digitalization. Tool-based technologies require teachers, either as individuals or as groups, to innovate and come up with designs and ideas to implement them in various teaching and learning activities.
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Program-based technologies, on the other hand, are the ones that are specifically designed for pedagogical purposes with premade learning content delivered through algorithm-enabled instruction, such as learning games and online personalized learning programs that use artificial intelligence to give each student individualized academic exercises. They are often developed by companies and large not-for-profit organizations. They give classroom teachers less control over the design and content. They are designed to replace considerable portions of teachers’ traditional work, such as delivery of instruction. Teachers and schools tend to focus on managing the logistics for the implementation of such technologies to fit into their learning goals. Program-based technologies are relatively new, emerging with the advancement of artificial intelligence. These technologies have received tremendous attention, largely due to Silicon Valley’s increasing interest in this field. For example, Facebook founder Mark Zuckerberg, through his Chan Zuckerberg Initiative, developed the Summit Learning Program to promote online personalized learning of core subjects of grades 4–12 [5].
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Digitalized contents, such as e-books, slide shows, YouTube videos, TED Talks, and online curricula teachers create or download online for self-learning or assisting teaching activities, are still considered tool-based technologies, despite their pre-made educational contents. They are created using tool-based technologies and rely on teachers to design their classroom use. The same logic applies to some learning management platforms that have been widely adapted, such as Canvas and Blackboard, to help teachers to assign homework and more effectively maintain online learning materials and students’ records. Although they are made specifically for educational purposes, they represent an integration of traditional technological tools to assist teachers instead of being designed to replace teachers’ pedagogical functionalities (Figure 2).
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Figure 2.
Categorization of educational technologies.
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3. Adoption of tool-based technologies
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Most studies on teachers’ use of technology refer to the use of tool-based technologies. Teachers’ successful adoption of this kind of technology, for themselves to either motivate students or deliver instructions more efficiently or for students to engage in learning activities using technology, depends on three crucial factors: professional support, teachers’ attitude, and learning goals.
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The use of tool-based technologies in educational settings highly depends on teachers’ competency to innovate and design. A misconception is that the introduction of technological tools to schools is equivalent to the introduction of educational technologies. On the contrary, teachers tend not to innovate when technologies are provided [6]. Teachers need to develop knowledge and skills to employ technological tools for educational purposes. Therefore, adequate professional support is needed, so teachers will be able to master the effective use of technologies specifically within a classroom setting. Teachers who have received professional development are more proficient in using technologies and are more likely to use them, whereas without professional development, teachers are not only less proficient but also likely to resist integration of technologies [4, 7]. Unfortunately, educational technology training is lacking in teacher preparation programs in universities [8]. Thereafter, in the teaching field, the majority of teachers only receive <8 h of professional development on educational technology annually [9].
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A successful professional development program needs to pay attention to both its content and its format. It should contain content knowledge in three areas [10]:
Knowledge about technological tools: technical knowledge that helps teachers to become equipped with skills to use hardware and software
Technology-supported pedagogical knowledge: specific knowledge and skills that teachers need to learn that help them to use technology to design materials, deliver instructions, or engage students to achieve the learning goals in specific academic domains
Knowledge about technology-related classroom management: knowledge giving teachers insight into students’ reaction in a tech-infused learning environment, for example, how to prevent students from using the devices and the Internet to do inappropriate activities in disguise.
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The effectiveness of such a program is closely tied to a school’s ability to develop a supportive learning community [7, 11, 12]. Professional development programs on educational technologies work less efficiently when they are only content- and knowledge-based; communication and interaction are of high significance [10]. A successful professional development program should be a place where:
Teachers can discuss their tangible and immediate needs related to the use of technologies [7, 13].
Teachers can share successful examples of the use of technologies in real educational settings [14, 15].
Teachers can have opportunities to work with knowledgeable peers [11].
Teachers have adequate time to explore the technologies on their own [4, 16].
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Learning with real examples in the field created by peers has been proven to be essential in professional development. This is also true of teacher preparation programs. Preservice teachers who have real in-school experience learning about technologies in real educational practices are more likely to succeed [8, 14, 15, 17, 18]. To leverage the power of tool-based technologies in teaching and learning, educational technology training should be very content-specific—for example, how to use the visual features of PowerPoints to demonstrate abstract geometry concepts in math classes and how to guide students to make an online survey in social studies. It is crucial that teachers do not receive vague information in professional development but rather have opportunities to discuss and learn specific techniques to assist immediate pedagogical needs with peers.
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Teachers’ attitude toward the effectiveness of technology affects the adoption of tool-based technologies as well. Such effects can be played out on both personal and interpersonal levels. Teachers who individually believe technologies will help them conduct better education are more likely to succeed at using them [15, 16, 19, 20]. Many of these teachers believe that technologies can help to better engage students, introduce project-based learning, help students access more information, and enhance communication and collaborative learning [21, 22, 23]. However, it is common for teachers to hold negative impressions toward the use of certain technologies, which makes it harder for them to integrate those technologies [19, 24, 25]. This situation often happens when teachers are not given sufficient information and training to learn the specific benefits of technologies, which leads them to worry about risking educational resources and teaching time to integrate unnecessary or potentially detrimental technologies [26, 27]. Additional common negative attitudes among teachers include fear of losing control over technologies, technological misfunction and lack of IT support, and concerns about the lack of time to adjust to new pedagogical practices, risking student test scores [26, 27, 28].
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On the interpersonal level, experienced teachers’ attitude toward technology significantly influences young professionals’ impressions about technology. When experienced teachers exhibit a more positive and welcoming attitude toward technology, that often translates into a school culture that embraces technology and encourages teachers to support one another in terms of developing and designing learning programs that take specific advantage of technology [24, 25]. Moreover, a positive attitude among teachers also translates into positive attitudes toward education among students and better learning engagement [29].
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Research also shows that teachers who believe technologies can help them transform from lecture-based learning to student-centered learning are more likely to welcome technologies [21, 23]. Therefore, the foundation provided by a school’s learning goals, often reflected in institutional policy as well as practice, also significantly affects teachers’ adoption of technologies [7, 16, 30]. Teachers tend to avoid technologies if they believe technologies, even if helpful, deviate from the school’s learning goals [31]. For example, teachers may believe certain technologies can help students to do collaborative projects, but given the limited time and pressure from standardized testing, teachers may choose to teach to tests instead of integrating the technologies for new learning tasks.
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Our current education model was largely invented for and defined by the Industrial Revolution, designed to meet the need of massive labor demand with standardized skill sets [32]. The advantage of technology has been restricted by the nature of our traditional education paradigm, where teaching and learning occur in a mechanical way with learning goals aimed at the mastery of knowledge. This learning goal can be very often achieved by traditional pedagogical techniques that do not require technological integration, such as direct instruction. Therefore, teachers often do not see the need to use technologies to conduct education in an efficient way to help students to achieve learning outcomes set by graduation standards and measured by standardized testing [1]. On the other hand, teachers are likely to have a positive impression of technology if they believe in constructivist learning [33, 34]. From a constructivist perspective, technology can serve as a powerful tool for both teachers and students to conduct research, assist in self-directed learning, and design and produce media-infused projects. Indeed, teachers tend to increase the use of technology if the learning goals are set up to be student-centered and project-based, focused on high-level skills such as creativity, research, and critical thinking [7, 21].
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3.1 A need to redefine learning goals
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Fundamentally, technologies should be offered as a way to achieve schools’ learning goals, and the question we should ask is: What can we do now with technology that was not possible before? [1]. However, very often, we do not have an identified problem in education that we hope technologies can help us solve, and we do not have a clear goal or expectation about how technology should be positioned in education to help with our learning goals [35]. We realize that technologies are something good to have, and it seems irresponsible if we fail to harness this power for education. Therefore, we have introduced technologies into schools, without changing any of our traditional practices, in an effort to enact their great potential. Instead, what we have largely done is carve out some tiny spaces for technology to fit into the traditional learning paradigm. If we go into a classroom, we will find out that the most popular technologies in schools are projectors, document cameras, and smartboards. Those technologies are helpful, but not necessary; the functions they perform could be done adequately before we had technology. Teachers who see technologies merely as supplemental tools for instruction are less likely to successfully adopt them [7]. Technology in today’s school setting gives teachers a third hand. It is something good to have, as it allows teachers to accomplish some tasks in a more convenient and efficient way [36]. However, its existence only brings quantitative difference without qualitative difference to the advancement of pedagogical practices [35]. Teachers who are experienced in teaching without technologies often do not see the necessity of having them [24, 25, 30]. Therefore, a true, successful adoption of tool-based technologies in education should start at the institutional level by redefining the learning goals that cannot be accomplished without technologies. For example, if our learning goals go beyond mastering of testable knowledge that can be obtained through direct instruction to creative and collaborative skills in project-based learning, we would arrange our class in such a way that students, under teachers’ guidance, could conduct research on the Internet and produce digital media such as videos and PowerPoint presentations.
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Tool-based technologies are only as good as the way in which they are used by teachers. These technologies are not educational in nature but rather require teachers, through design and proper implementation, to transform technological tools into tool-based technologies that enhance teaching and learning. In the case of tool-based technologies, this adoption process is more important than the technologies themselves. Therefore, teachers are the key instead of machines, and teachers need to have the incentive and adequate skills to realize the process. Unfortunately, schools tend to spend tremendous resources to purchase and maintain equipment but often neglect to invest in helping teachers to adopt them [37]. The adoption process starts with redefining learning goals. Learning goals that demand less mechanical learning of content knowledge and value high-level skills—aligned with student-centered, constructivist learning and creative instruction—motivate teachers to see the unique value of technologies and develop a positive attitude toward their use. Suitable learning goals set direction for professional development for both preservice teachers in universities and in-service teachers in the field. Positive attitudes create a solid foundation for a collaborative learning community to take place, which helps teachers to be equipped with sufficient content knowledge and skills for adopting technologies to assist pedagogical practices. An efficient and thorough change starts with redefining learning goals, which are hopefully initiated top-down. The role of school leaders and experienced teachers is of the utmost importance (Figure 3).
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Figure 3.
Teachers’ adoption of tool-based educational technologies.
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4. Double-faced program-based technologies
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With recent advances in technology, we have entered the Information Era, especially after the invention of the Internet. Technology made digitalized content become the main resource from which we gain information and knowledge [38]. If we think of learning as a broad, lifelong process, most knowledge we learn today is not in classrooms. With technology, we expand the learning environment, which means that learning is no longer restricted to formal classroom instruction. Some believe that if we focus solely on the work of passing information and knowledge, technology is probably able to replace some components of traditional teaching. Others predict that mobile learning will partially take the place of teachers [39]. Mobile learning has several advantages. First, technology makes information and knowledge more accessible, and students can access more enriched resources of information through mobile learning. Second, learning environments can be expanded, and as long as students can access technology, they can learn anything, anytime, and anywhere. Third, mobile learning allows students to customize learning [40]. Among all the expected benefits, personalization of education has stirred up the most hope—traditionally, dozens of students receive the same information from one teacher in a classroom. However, with technology, every student has the opportunity to learn topics that have been individually tailored. Using technologies to fulfill personalized education has recently attracted tremendous attention from Silicon Valley, fueled with hundreds of millions of dollars from the Chan Zuckerberg Initiative [5, 41]. A program developed out of this initiative is called Summit Learning, which has been collaborating with hundreds of US schools to implement its personalized learning programs. These programs deliver individualized learning content of core academic subjects of grades 4–12, from a computer to a student, with the hope that students will study better with technologies than teachers [5]. These personalized learning programs are given to individual students based on an analysis of their learning attributes using an artificial intelligence algorithm. In such programs, technologies and learning contents included have been predeveloped by technology companies that give teachers little autonomy over the balance of teaching between teachers and machines. Also, many aspects of how the algorithm works often reside in a black box, remaining largely unknown to teachers or researchers. Learning through these technological programs, or, in other words, program-based technologies, is a fundamentally different pedagogical practice and learning experience than the use of tool-based technologies, which are still largely driven by teachers. However, program-based technologies are primarily driven by digital programs.
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4.1 The promise of program-based technologies
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Although in the technology industry such distinction has been seldom made, the field of educational research has classified personalized education into two categories: outcome personalization and process personalization [42]. Outcome personalization gives students autonomy in the learning process. Many student-centered, project-based learning programs are designed in such a way that students may design a project of their choice, while the education process helps students to master necessary skills and knowledge to achieve the project. Outcome personalization is often filled by tool-based technologies, which give both teachers and students more creative power. However, most program-based technologies are used to fulfill process personalization, which gives students little choice over the learning process. Students are merely given customized learning materials selected based on computer algorithms, and the end goal of the process is to help students achieve standardized learning goals. In essence, program-based technologies could sufficiently fit into the demand of the traditional educational paradigm that emphasizes mastering standardized knowledge and skills. If implemented well, program-based technologies are expected to replace a considerable portion of teachers’ functionality.
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Advocates for the use of program-based technologies in personalized education believe that technologies can do a better job than traditional teachers because these technologies can unremittingly monitor individual students’ learning progress and simultaneously provide learning contents that are most suitable to individual students’ habits and learning attributes [43]. With a highly sophisticated algorithm, big data, and a large pool of well-tailored contents, technologies are expected to have certain advantages over human teachers in terms of delivering more effective instruction to each student. Additionally, advocates believe that technologies are more economically efficient and more accessible than human teachers, which can help to scale up good education and improve equity and equalization in education [40, 43]. Finally, teachers could be liberated from the mechanical work of teaching students basic knowledge and skills so they could be more focused on helping students with additional higher-level learning.
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4.2 The problems of program-based technologies
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Before using artificial intelligence for personalized learning, program-based technologies were largely made of learning games, with the hope that learning could be delivered in an attractive format. However, the downfall came when it became more and more clear that most educational games were not as attractive to students as regular computer games, and students easily lost interest over time [44, 45]. As a consequence, the interest in learning games has been gradually disappearing in the industry. Unfortunately, personalized learning technologies seem to share the fate of learning games—not only the fate of failure but also the specific inability to engage and motivate students in the learning process.
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Very little research has been conducted on the effectiveness of Summit Learning’s personalized learning technologies; nor has there been much research on other program-based technologies on personalized learning [45]. Besides questionable learning outcomes, these technologies face tremendous challenges due to students’ negative reaction toward the learning experience under such programs. A study shows that students significantly feel less engaged in and experience less enjoyment in school due to lack of human interaction [46, 47]. Also, there have been news reports showing that personalized learning technologies face backlash among students and parents. Some students claim they feel they were like zombies sitting in front of computers all day long [41]. The intangible “joy” of learning, so often derived from human discussion and interaction, seems to be compromised by such programs. Overall, concerns about these technologies are as follows: they reduce students’ reported joy of learning; jeopardize students’ bond with teachers, while a healthy relationship between children and adults is essential in their development; isolate students; encourage unhealthy competition by exposing the difference in students’ learning progress; and are prone to misuse of student data by big corporations [48]. With all these perceived negative images in the public arena, it is not hard to assert that current efforts of using program-based technologies to conduct personalized education to replace teachers, represented by Summit Learning, will be far from successful. However, there is not much rigorous evaluation of such programs through imperial research, nor does it seem that the developers of these programs have any immediate intention to grant access to scholars to conduct any evaluation.
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4.3 A need for research on program-based technologies
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Given that program-based technologies in education are largely developed by the technology industry instead of educators or educational researchers, as well as a special commercial interest in the industry, those technologies have seldom been well-examined in an empirical way, nor have their developers been given the incentive to conduct considerable research or comprehensive program evaluation. Chan Zuckerberg’s Initiative originally planned to work with the Harvard Graduate School of Education to examine the effectiveness of its Summit Learning Program, but it was called off by the initiative before the research started [41]. By the time this paper was written, we still did not know, despite students’ negative emotional reaction toward the program, whether the program could deliver its academic promises. Many factors may determine the success of program-based technologies, such as the content of learning materials, the artificial intelligence or other algorithms to assess students’ learning progress, and the implementation in school settings in relation to teachers’ assistance and other school activities. Many of the promises of technology-enabled personalized learning do not lose their attraction because of the failure of a first attempt. Future research is urgently needed to comprehensively examine these new technologies.
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The significance and advantage of human teachers cannot be easily replaced. Although knowledge can be easily accessed through program-based technologies, a lack of human interaction and motivation results in reduced knowledge acquisition among students. As learning is not a mechanical cognitive activity, students’ negative emotions could lead to not learning, which does not refer to being incapable of learning but a term describing the psychological state of resistance to participation in learning activities [49]. It is highly possible that program-based technologies could never work alone. They might need to open space to work closely with human teachers to be effective. Unlike tool-based technologies, which have been thoroughly researched, the adoption of program-based technologies has seldom been studied. Many do not even see the distinction between those two groups. We urge the industry and the scientific community to conduct more research on program-based technologies, which will surely open a new frontier in our understanding of the use of educational technologies in pedagogical practices, as what it takes to adopt teacher-driven tool-based technologies could be vastly different from newly emerged algorithm-driven program-based technologies. We suggest not only to research the technologies themselves, including their learning contents and algorithm, but also how these technologies are positioned in the ecological system in school and how human interaction can work together with the algorithm.
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5. Conclusion and a look into the future
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It has been a long-held misconception that educational technologies are homogeneous and they behave in a similar way in relation to teachers’ adoption and school implementation, among other factors. It is an oversight in the field of educational research that we have seldom made any distinction in the kinds of technologies that have been used in schooling, instead often studying them in a singular set. This was not an influential mistake when most technologies used in pedagogical practices were tool-based technologies and indeed shared many similarities. However, with the recent introduction of artificial intelligence into personalized education, new categories of technologies have emerged that are drastically distinct from the ones before. Therefore, a careful categorization of educational technologies should be made to help us study issues on educational technology in a well-structured way. Educational technologies are composed of pedagogical technologies (used in direct participation of teaching and learning activities) and operational technologies (used in the operative and administrative work of teachers).
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Pedagogical technologies can be further split into two groups: tool-based technologies and program-based technologies. Tool-based technologies are the most common, have a longer history, and have been well-researched. They refer to technologies that are not specifically designed for educational purposes and are versatile tools in nature. Teachers’ adoption of these technologies through a process of design and implementation transforms these technological tools into pedagogical technologies that assist in teaching and learning. Teachers are less inclined to use tool-based technologies if they are considered supplemental instructional tools for efficient lectures. On the other hand, teachers are more likely to use such technologies for student-centered constructivism learning because of technologies’ power to hone creative and critical thinking skills. Therefore, efficient adoption needs to be top-down, starting by setting learning goals that demand high-level creative skills instead of the mechanical acquisition of content knowledge. Suitable learning goals motivate teachers to see the value of developing positive attitudes toward technologies, which should fuel professional development programs, which should not only deliver adequate content knowledge but also create supportive and collaborative learning communities among preservice and in-service teachers. As such, teachers could be equipped with the skills, knowledge, and emotional drive to adopt tool-based technologies.
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Program-based technologies are predeveloped with learning contents that are delivered to students in a preprogrammed way. They leave less control to teachers and instead drive learning by their own artificial intelligence or other program algorithms. Although there has been high hope that they could replace teachers’ instruction to provide students with a personalized learning experience, the lack of human interaction often makes students feel less engaged in schooling and results in learning resistance. More research should be conducted in this field to study these technologies and the possibility of teachers working with algorithms in a more collaborative way instead of a either teacher or computer modal.
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Technologies bring the Information Era to schools. As the economy has shifted from labor-demanding to innovation-demanding, learning of basic skills and content knowledge is far from enough. A new competence set of creativity, collaborative learning, and research is more valuable than ever, which translates into new learning goals that demand students to be innovative and proactive learners. Technologies can help with that, but, without question, the role of teachers is still critical. Technologies cannot exclude teachers but should rather work with teachers to transform education from instruction-centered to student-centered. Tool-based technologies give teachers the means to be innovative and achieve that goal. Program-based technologies should be developed in a way that work seamlessly with teachers through research-based practices, instead of repeating the failure of pursuing student-centered learning by replacing teachers. After all, information can be digitalized, but learning itself is still a very human business.
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\n\n',keywords:"educational technologies, pedagogical practices, teaching and learning, artificial intelligence",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/68730.pdf",chapterXML:"https://mts.intechopen.com/source/xml/68730.xml",downloadPdfUrl:"/chapter/pdf-download/68730",previewPdfUrl:"/chapter/pdf-preview/68730",totalDownloads:439,totalViews:0,totalCrossrefCites:0,dateSubmitted:"April 29th 2019",dateReviewed:"July 16th 2019",datePrePublished:"August 23rd 2019",datePublished:null,dateFinished:null,readingETA:"0",abstract:"Educational technologies are not homogeneous. This chapter proposes a framework to categorize various technologies in the K-12 educational setting into groups of operational technologies and pedagogical technologies by whether they directly participate in the process of teaching and learning. Furthermore, pedagogical technologies are split into tool-based and program-based technologies based on whether they are teacher-driven tools or algorithm-driven learning programs. Efficient adoption of tool-based technologies requires a redefinition of learning goals to embrace student-centered education. Program-based technologies need more research to be fully understood and improved, and current ones are under-researched and fail to engage and motivate students to learn.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/68730",risUrl:"/chapter/ris/68730",signatures:"Perry P. Gao, Arvid Nagel and Horst Biedermann",book:{id:"9040",title:"Pedagogy in Basic and Higher Education",subtitle:"Current Developments and Challenges",fullTitle:"Pedagogy in Basic and Higher Education - Current Developments and Challenges",slug:"pedagogy-in-basic-and-higher-education-current-developments-and-challenges",publishedDate:"February 19th 2020",bookSignature:"Kirsi Tirri and Auli Toom",coverURL:"https://cdn.intechopen.com/books/images_new/9040.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"234399",title:"Prof.",name:"Kirsi",middleName:null,surname:"Tirri",slug:"kirsi-tirri",fullName:"Kirsi Tirri"}],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. Categorization of educational technologies",level:"1"},{id:"sec_2_2",title:"2.1 Pedagogical technologies vs. operational technologies",level:"2"},{id:"sec_3_2",title:"2.2 Tool-based technologies vs. program-based technologies",level:"2"},{id:"sec_5",title:"3. Adoption of tool-based technologies",level:"1"},{id:"sec_5_2",title:"3.1 A need to redefine learning goals",level:"2"},{id:"sec_7",title:"4. Double-faced program-based technologies",level:"1"},{id:"sec_7_2",title:"4.1 The promise of program-based technologies",level:"2"},{id:"sec_8_2",title:"4.2 The problems of program-based technologies",level:"2"},{id:"sec_9_2",title:"4.3 A need for research on program-based technologies",level:"2"},{id:"sec_11",title:"5. Conclusion and a look into the future",level:"1"}],chapterReferences:[{id:"B1",body:'Peck KL, Dorricutt D. Why use technology? Educational Leadership. Alexandria. 1994;51(7):11\n'},{id:"B2",body:'Cuban L. Oversold and Underused: Computers in the Classroom. Cambridge, MA: Harvard University Press; 2001\n'},{id:"B3",body:'Trends in Digital Learning: Building teachers’ capacity and competency to create new learning experiences for students. Project Tomorrow [Internet]. 2017. Available from: https://tomorrow.org/speakup/speak-up-2016-trends-digital-learning-june-2017.html [Accessed: 15 July 2019]\n'},{id:"B4",body:'Aldunate R, Nussbaum M. Teacher adoption of technology. Computers in Human Behavior. 2013;29(3):519-524\n'},{id:"B5",body:'Summit Learning is spreading with little evidence of success [Internet]. Chalkbeat. 2019. Available from: https://chalkbeat.org/posts/us/2019/01/17/summit-learning-research-harvard/ [Accessed: 18 June 2019]\n'},{id:"B6",body:'Zhao Y, Pugh K, Sheldon S, Byers JL. Conditions for classroom technology innovations. Teachers College Record. 2002;104(3):482-515\n'},{id:"B7",body:'Ertmer PA, Ottenbreit-Leftwich AT. Teacher technology change: How knowledge, confidence, beliefs, and culture intersect. Journal of Research on Technology in Education. 2010;42(3):255-284\n'},{id:"B8",body:'Tondeur J, van Braak J, Sang G, Voogt J, Fisser P, Ottenbreit-Leftwich A. Preparing pre-service teachers to integrate technology in education: A synthesis of qualitative evidence. Computers & Education. 2012;59(1):134-144\n'},{id:"B9",body:'Gray L, Thomas N, Lewis L. Teachers\' Use of Educational Technology in US Public Schools: 2009. First Look. NCES 2010-040. National Center for Education Statistics; 2010\n'},{id:"B10",body:'Hew KF, Brush T. Integrating technology into K-12 teaching and learning: Current knowledge gaps and recommendations for future research. Educational Technology Research and Development. 2007;55(3):223-252\n'},{id:"B11",body:'Ertmer PA, Ottenbreit-Leftwich A, York CS. Exemplary technology-using teachers: Perceptions of factors influencing success. Journal of Computing in Teacher Education. 2006;23(2):55-61\n'},{id:"B12",body:'Putnam RT, Borko H. What do new views of knowledge and thinking have to say about research on teacher learning? Educational Research. 2000;29(1):4-15\n'},{id:"B13",body:'Kanaya T, Light D, McMillan Culp K. Factors influencing outcomes from a technology-focused professional development program. Journal of Research on Technology in Education. 2005;37(3):313-329\n'},{id:"B14",body:'Albion PR, Ertmer PA. Beyond the foundations: The role of vision and belief in teachers’ preparation for integration of technology. TechTrends. 2002;46(5):34-38\n'},{id:"B15",body:'Zhao Y, Cziko GA. Teacher adoption of technology: A perceptual control theory perspective. Journal of Technology and Teacher Education. 2001;9(1):5-30\n'},{id:"B16",body:'Demetriadis S, Barbas A, Molohides A, Palaigeorgiou G, Psillos D, Vlahavas I, et al. “Cultures in negotiation”: Teachers’ acceptance/resistance attitudes considering the infusion of technology into schools. Computers in Education. 2003;41(1):19-37\n'},{id:"B17",body:'Ottenbreit-Leftwich AT, Glazewski KD, Newby TJ, Ertmer PA. Teacher value beliefs associated with using technology: Addressing professional and student needs. Computers in Education. 2010;55(3):1321-1335\n'},{id:"B18",body:'Ertmer PA, Conklin D, Lewandowski J, Osika E, Selo M, Wignall E. Increasing preservice teachers\' capacity for technology integration through the use of electronic models. Teacher Education Quarterly. 2003;30(1):95-112\n'},{id:"B19",body:'Mueller J, Wood E, Willoughby T, Ross C, Specht J. Identifying discriminating variables between teachers who fully integrate computers and teachers with limited integration. Computers in Education. 2008;51(4):1523-1537\n'},{id:"B20",body:'Subramaniam K. Teachers\' mindsets and the integration of computer technology. British Journal of Educational Technology. 2007;38(6):1056-1071\n'},{id:"B21",body:'Anthony AB, Clark LM. Examining dilemmas of practice associated with the integration of technology into mathematics classrooms serving urban students. Urban Education. 2011;46(6):1300-1331\n'},{id:"B22",body:'Culp KM, Honey M, Mandinach E. A retrospective on twenty years of education technology policy. Journal of Educational Computing Research. 2005;32(3):279-307\n'},{id:"B23",body:'Jonassen DH, Howland JL, Moore J, Marra RM. Learning to Solve Problems with Technology: A Constructivist Perspective. Upper Saddle River, NJ: Merrill; 2003\n'},{id:"B24",body:'Abbott JA, Faris SE. Integrating technology into preservice literacy instructions a survey of elementary education students’ attitudes toward computers. Journal of Research on Computing in Education. 2000;33(2):149-161\n'},{id:"B25",body:'Hazzan O. Prospective high school mathematics teachers’ attitudes toward integrating computers in their future teaching. Journal of Research on Computing in Education. 2002;35(2):213-225\n'},{id:"B26",body:'Howard SK. Risk-aversion: Understanding teachers’ resistance to technology integration. Technology, Pedagogy and Education. 2013;22(3):357-372\n'},{id:"B27",body:'Lei J. Quantity versus quality: A new approach to examine the relationship between technology use and student outcomes. British Journal of Educational Technology. 2010;41(3):455-472\n'},{id:"B28",body:'Tondeur J, van Braak J, Ertmer PA, Ottenbreit-leftwich A. Understanding the relationship between teachers’ pedagogical beliefs and technology use in education: A systematic review of qualitative evidence. Educational Technology Research and Development. 2017;65(3):555-575\n'},{id:"B29",body:'Christensen R. Effects of technology integration education on the attitudes of teachers and students. Journal of Research on Technology in Education. 2002;34(4):411-433\n'},{id:"B30",body:'Hennessy S, Ruthven K, Brindley S. Teacher perspectives on integrating ICT into subject teaching: Commitment, constraints, caution, and change. Journal of Curriculum Studies. 2005;37(2):155-192\n'},{id:"B31",body:'Zhao Y, Frank KA. Factors affecting technology uses in schools: An ecological perspective. American Educational Research Journal. 2003;40(4):807-840\n'},{id:"B32",body:'Gao P. Using personalized education to take the place of standardized education. Journal of Education and Training Studies. 2014;2(2):44-47\n'},{id:"B33",body:'Judson E. How teachers integrate technology and their beliefs about learning: Is there a connection? Journal of Technology and Teacher Education. 2006;14(3):581-597\n'},{id:"B34",body:'Alfelaij B. Why integrating technology has been unsuccessful in Kuwait? An exploratory study. E-Learning and Digital Media. 2016;13(3-4):126-139\n'},{id:"B35",body:'Zhao Y. What Should Teachers Know about Technology: Perspectives and Practices. Greenwich, CT: Information Age; 2004;2:1\n'},{id:"B36",body:'Gullen K, Zimmerman H. Saving time with technology. Education Leader. 2013;70(6):63-66\n'},{id:"B37",body:'Lim CP, Zhao Y, Tondeur J, Chai CS, Tsai CC. Bridging the gap: Technology trends and use of technology in schools. Journal of Educational Technology & Society. 2013;16(2):59-68\n'},{id:"B38",body:'Castells M. The Rise of the Network Society. Chichester, West Sussex: Wiley-Blackwell; 2010\n'},{id:"B39",body:'Sharples M, Taylor J, Vavoula G. A theory of learning for the mobile age. In: Medienbildung in Neuen Kulturräumen. VS Verlag für Sozialwissenschaften; 2010. pp. 87-99\n'},{id:"B40",body:'Johnson L, Becker SA, Cummins M, Estrada V, Freeman A, Hall C. NMC horizon report: 2016 higher education edition. The New Media Consortium; 2016\n'},{id:"B41",body:'Bowles N. Silicon Valley Came to Kansas Schools. That Started a Rebellion. The New York Times [Internet]. 2019. Available from: https://www.nytimes.com/2019/04/21/technology/silicon-valley-kansas-schools.html [Accessed: 30 June 2019]\n'},{id:"B42",body:'Zhao Y, Tavangar H, McCarren E, Rshaid GF, Tucker K. The Take-Action Guide to World Class Learners Book 1: How to Make Personalization and Student Autonomy Happen. Corwin Press; 2015\n'},{id:"B43",body:'McKnight K, O’Malley K, Ruzic R, Horsley MK, Franey JJ, Bassett K. Teaching in a digital age: How educators use technology to improve student learning. Journal of Research on Technology in Education. 2016;48(3):194-211\n'},{id:"B44",body:'Hwang G, Sung H, Hung C, Huang I, Tsai C. Development of a personalized educational computer game based on students’ learning styles. Educational Technology, Research and Development. 2012;60(4):623-638\n'},{id:"B45",body:'Hoffman B, Nadelson L. Motivational engagement and video gaming: A mixed methods study. Educational Technology Research and Development. 2010;58(3):245-270\n'},{id:"B46",body:'Pane JF, Steiner ED, Baird MD, Hamilton LS. Continued progress: Promising evidence on personalized learning. Santa Monica, CA: RAND Corporation; 2015\n'},{id:"B47",body:'Barnum M. Don’t just talk about tech: How “personalized learning” advocates are honing their messaging. Chalkbeat [Internet]. 2018. Available from: https://www.chalkbeat.org/posts/us/2018/04/13/dont-just-talk-about-tech-how-personalized-learning-advocates-are-honing-their-messaging/ [Accessed: 19 June 2019]\n'},{id:"B48",body:'Wexler N. Mark Zuckerberg’s Plan To “Personalize” Learning Rests on Shaky Ground. Forbes [Internet]. 2018. Available from: https://www.forbes.com/sites/nataliewexler/2018/04/19/mark-zuckerbergs-plan-to-personalize-learning-rests-on-shaky-ground/ [Accessed: 19 June 2019]\n'},{id:"B49",body:'Gao P. I love to learn, but I hate to be taught. Journal of Education and Training Studies. 2014;2(3):104-107\n'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Perry P. Gao",address:"perry_gao@mail.harvard.edu",affiliation:'
Harvard Graduate School of Education, Education Bridge Institute, USA
St. Gallen University of Teacher Education, Switzerland
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The Open Access model is applied to all of our publications and is designed to eliminate subscriptions and pay-per-view fees. This approach ensures free, immediate access to full text versions of your research.
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English language copyediting and proofreading, including the correction of grammatical, spelling, and other common errors
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XML Typesetting and pagination - web (PDF, HTML) and print files preparation
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Exceeds 20 pages (for chapters in Edited Volumes), an additional fee of 40 GBP per page will be required
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For Authors who are still unable to obtain funding from their institutions or research funding bodies for individual projects, IntechOpen does offer the possibility of applying for a Waiver to offset some or all processing feed. Details regarding our Waiver Policy can be found here.
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+146,150 citations in Web of Science databases
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Currently strongest OA platform with over 130 million downloads
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