Chapters authored
Comprehensive Overview of Alzheimer’s Disease Neurodegeneration, from Amyloid-β to Neuroinflammatory Modulation
Alzheimer’s disease (AD) constitutes a major health threat to elder people. Despite the great advances achieved regarding our knowledge of the disease, we are far to successfully treat this pathology. Molecular alterations, immune/inflammatory response, and cell death are some of the processes involved during the pathology. Moreover, AD affects the whole brain. In this regard, we must not only consider the health status of neurons, of course, but also pay attention to the status of the glial cells and additional surrounding structures, such as the blood-brain barrier (BBB). Several groups have demonstrated how the molecular alterations occurring during AD alter neurons, glial, and endothelial cells. This situation has become so relevant that different groups are currently working to unveil the blank spaces in our understanding about the co-involvement of these elements in AD. Based in our experience, we believe that this kind of approach will lead to the design and development of more comprehensive therapeutical interventions. The present chapter summarizes the relevant aspects of state of the art regarding AD, from its molecular genesis to the recent advances in neuroinflammatory modulation, including nuclear receptors (NR), such as peroxisome proliferator-activated receptors (PPARs), and the Wnt pathway involved in the AD neurodegeneration.
Part of the book: Mechanisms of Neuroinflammation
Molecular Basis of Neurodegeneration: Lessons from Alzheimer’s and Parkinson’s Diseases
Alzheimer’s disease (AD) and Parkinson’s disease (PD) constitute the main causes of dementia worldwide and the major health threats to elderly people. Moreover, with the ageing of the global population, neurodegenerative disorders, such as AD and PD, constitute a major public health issue. Regrettably, significant advances regarding the molecular aspects of these diseases have not yet been translated into real improvements in AD/PD therapeutics. In this regard, both AD and PD are highly complex and involve critical molecular events governing the establishment and progression of each disease. Moreover, molecular alterations trigger pathophysiological cascades involving the immune/inflammatory response, oxidative stress, and mitochondrial dysfunction, among others, ultimately leading to neuronal death. Similarly, these alterations also affect glial cells and brain vasculature, which contribute directly to the progression of these disorders. Accordingly, the present paper aims to summarise the main molecular elements related to AD and PD as well as the pathophysiological implications of such alterations to improve our understanding of the cellular and molecular responses observed during neurodegeneration. We believe that providing a more comprehensive view of the pathophysiological cascade, including neurons and glial cells, might prompt researchers to widen neurodegenerative disorder research and therapeutic approaches.
Part of the book: Recent Advances in Neurodegeneration
Toll-Like Receptors (TLRs) in Neurodegeneration: Integrative Approach to TLR Cascades in Alzheimer’s and Parkinson’s Diseases
Sterile inflammatory response constitutes a main event in several neurodegenerative disorders. Alzheimer’s disease (AD) and Parkinson’s disease (PD), the leading degenerative pathologies of the central nervous system worldwide, exhibit a strong inflammatory component. Microglial and astrocytic reactivity, increased levels of inflammatory mediators, neuronal damage, and death are part of the pathological scenario leading to the progressive failure of the brain neuronal network. In this regard, the link between the toll-like receptors (TLRs)-mediated inflammatory cascade and the molecular hallmarks of AD and PD have been demonstrated elsewhere. Moreover, the long-lasting exposure to the inflammatory environment is considered one of the key elements leading to the establishment and progression of these pathologies. Accordingly, the modulation of the inflammatory response has emerged as a main target of new therapeutic approaches to fight these diseases. In this regard, and based on our previous works on this subject, we describe the pathological profile of both pathologies but in the inflammatory context. Thus, in the present chapter, we will introduce the main aspects of both diseases and how they interplay with the TLR-mediated response. We believe that this chapter should provide a concise overview of the roles of TLRs in the inflammatory cascades triggered during AD and PD pathophysiology.
Part of the book: Toll-like Receptors