This exciting new book explores the dark side of the molecular protein assembly bringing an updated view of how failures in the homeostatic mechanisms that efficiently regulate protein folding leads to the accumulation of structurally abnormal pathogenic assemblies, encompassing an emerging group of diseases collectively known as 'Protein Folding Disorders.' This complex and diverse group of chronic and progressive entities are bridged together by their relationship to structural transitions in the native state of specific proteinaceous components, which for reasons poorly understood, convert into polymeric aggregates that generate poorly soluble tissue deposits and which are considered today the culprit of the disease pathogenesis in their respective diseases. Despite the diversity in the amino acid sequence of the different proteins involved in these heterogeneous disorders, all the pathologic conformers can trigger cascades of events ultimately resulting in cell dysfunction and death with devastating clinical consequences in many of the most precious aspects of human existence including personality, cognition, memory, and skilled movements.This book, which is composed of a compilation of chapters authored by outstanding and well-published scientists in the respective fields currently performing active investigations at world renowned universities and research centers, focuses on the growing number of diseases associated with protein misfolding in the central nervous system. Individual chapters are dedicated to the most common neurodegenerative diseases associated with protein aggregation/fibrillization focusing on the nature of the pathogenic species and the cellular pathways involved in the molecular pathogenesis of Alzheimer's, Parkinson's, and Huntington's diseases as well as in Amyotrophic Lateral Sclerosis, and Prion disorders. A group of contributions is centered on the current knowledge of the intracellular pathways and subcellular organelles affected by the different disease conditions, while others are focused in the emerging pathogenic role of misfolded subunits assembled into neurotoxic soluble oligomers, and in the novel notion of the transmissibility of the protein misfolded species, an innovative concept until recently only accepted for Prion diseases. Lastly, a different set of chapters is dedicated to the evaluation of novel therapeutic strategies for these devastating diseases.

Neurofibrillary tangles (NFTs) composed of intracellular aggregates of tau protein are a key neuropathological feature of Alzheimer’s Disease (AD) and other neurodegenerative diseases, collectively termed tauopathies. The abundance of NFTs has been reported to correlate positively with the severity of cognitive impairment in AD. However, accumulating evidences derived from studies of experimental models have identified that NFTs themselves may not be neurotoxic. Now, many of tau researchers are seeking a “toxic” form of tau protein. Moreover, it was suggested that a “toxic” tau was capable to seed aggregation of native tau protein and to propagate in a prion-like manner. However, the exact neurotoxic tau species remain unclear. Because mature tangles seem to be non-toxic component, “tau oligomers” as the candidate of “toxic” tau have been investigated for more than one decade. In this topic, we will discuss our consensus of “tau oligomers” because the term of “tau oligomers” [e.g. dimer (disulfide bond-dependent or independent), multimer (more than dimer), granular (definition by EM or AFM) and maybe small filamentous aggregates] has been used by each researchers definition. From a biochemical point of view, tau protein has several unique characteristics such as natively unfolded conformation, thermo-stability, acid-stability, and capability of post-translational modifications. Although tau protein research has been continued for a long time, we are still missing the mechanisms of NFT formation. It is unclear how the conversion is occurred from natively unfolded protein to abnormally mis-folded protein. It remains unknown how tau protein can be formed filaments [e.g. paired helical filament (PHF), straight filament and twisted filament] in cells albeit in vitro studies confirmed tau self-assembly by several inducing factors. Researchers are still debating whether tau oligomerization is primary event rather than tau phosphorylation in the tau pathogenesis. Inhibition of either tau phosphorylation or aggregation has been investigated for the prevention of tauopathies, however, it will make an irrelevant result if we don’t know an exact target of neurotoxicity. It is a time to have a consensus of definition, terminology and methodology for the identification of “tau oligomers”.

The Molecular and Cellular Basis of Neurodegenerative Diseases: Underlying Mechanisms presents the pathology, genetics, biochemistry and cell biology of the major human neurodegenerative diseases, including Alzheimer's, Parkinson's, frontotemporal dementia, ALS, Huntington's, and prion diseases. Edited and authored by internationally recognized leaders in the field, the book's chapters explore their pathogenic commonalities and differences, also including discussions of animal models and prospects for therapeutics. Diseases are presented first, with common mechanisms later. Individual chapters discuss each major neurodegenerative disease, integrating this information to offer multiple molecular and cellular mechanisms that diseases may have in common. This book provides readers with a timely update on this rapidly advancing area of investigation, presenting an invaluable resource for researchers in the field. - Covers the spectrum of neurodegenerative diseases and their complex genetic, pathological, biochemical and cellular features - Focuses on leading hypotheses regarding the biochemical and cellular dysfunctions that cause neurodegeneration - Details features, advantages and limitations of animal models, as well as prospects for therapeutic development - Authored by internationally recognized leaders in the field - Includes illustrations that help clarify and consolidate complex concepts

This book highlights the pathophysiological complexities of the mechanisms and factors that are likely to be involved in a range of neuroinflammatory and neurodegenerative diseases including Alzheimer's disease, other Dementia, Parkinson Diseases and Multiple Sclerosis. The spectrum of diverse factors involved in neurodegeneration, such as protein aggregation, oxidative stress, caspases and secretase, regulators, cholesterol, zinc, microglia, astrocytes, oligodendrocytes, etc, have been discussed in the context of disease progression. In addition, novel approaches to therapeutic interventions have also been presented. It is hoped that students, scientists and clinicians shall find this very informative book immensely useful and thought-provoking.

Proper folding of proteins is crucial for cell function. Chaperones and enzymes that post-translationally modify newly synthesized proteins help ensure that proteins fold correctly, and the unfolded protein response functions as a homeostatic mechanism that removes misfolded proteins when cells are stressed. This book covers the entire spectrum of proteostasis in healthy cells and the diseases that result when control of protein production, protein folding, and protein degradation goes awry.

The synucleinopathy sporadic Parkinson’s disease (sPD) is the second most frequent degenerative disorder of the human nervous system after Alzheimer’s disease. The propensity for developing sPD exists in all ethnic groups worldwide, and the prevalence of the disorder increases considerably with age, thereby imposing an enormous social and economic burden on societies with increased life expectancy. The sPD-associated pathological process is progressive, does not go into remission, and can take decades to reach its culmination if it is not be terminated prematurely by death owing to other causes. Against the background of the normal morphology and anatomy, the authors analyze the pathoanatomy of sPD in the nervous system at various neuropathological stages and summarize the potential functional consequences of the lesions.

Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging is an eleven volume series that discusses in detail all aspects of autophagy machinery in the context of health, cancer, and other pathologies. Autophagy maintains homeostasis during starvation or stress conditions by balancing the synthesis of cellular components and their deregulation by autophagy. This series discusses the characterization of autophagosome-enriched vaccines and its efficacy in cancer immunotherapy. Autophagy serves to maintain healthy cells, tissues, and organs, but also promotes cancer survival and growth of established tumors. Impaired or deregulated autophagy can also contribute to disease pathogenesis. Understanding the importance and necessity of the role of autophagy in health and disease is vital for the studies of cancer, aging, neurodegeneration, immunology, and infectious diseases. Comprehensive and forward-thinking, these books offer a valuable guide to cellular processes while also inciting researchers to explore their potentially important connections. - Presents the most advanced information regarding the role of the autophagic system in life and death - Examines whether autophagy acts fundamentally as a cell survivor or cell death pathway or both - Introduces new, more effective therapeutic strategies in the development of targeted drugs and programmed cell death, providing information that will aid in preventing detrimental inflammation - Features recent advancements in the molecular mechanisms underlying a large number of genetic and epigenetic diseases and abnormalities, including atherosclerosis and CNS tumors, and their development and treatment - Includes chapters authored by leaders in the field around the globe—the broadest, most expert coverage available