Chemical Modulators Of Protein Misfolding And Neurodegenerative Disease

This book is a neurochemistry-based companion for Protein Misfolding and Neurodegenerative Diseases: Molecular Targets, an Elsevier title by the same author publishing in December 2014. While the first book focuses on biology and molecular targets, this companion book describes how these targets are regulated by small molecules and disease-modifying compounds. The book begins with a brief introduction to how key proteins become dysfunctional, and each subsequent chapter describes major disease mechanisms in Alzheimer’s and other tauopathies. Properties and development status of these molecular targets and disease mechanisms are thoroughly described, as are small molecule effectors of autophagy and dis-aggregating agents. Written to provide comprehensive coverage of neurodegenerative disease-modifying compounds Provides discipline-specific chapters that cover medicinal chemistry and clinical applications Provides an overview of more than 200 chemical classes and lead compounds, acting on selected molecular targets that are of relevance to any neurodegenerative disorder Coverage of misfolding diseases, chaperone proteins, ubiquitination and autophagy/oncology makes this book suitable for structural neurochemists, chemists, biologists, non-CNS scientists, and scientists interested in drug discovery

Aimed at "drug discoverers" – i.e. any scientist who is interested in neurodegenerative diseases in general, and in finding disease-modifying treatments in particular – the first edition of Molecular Targets in Protein Misfolding and Neurodegenerative Disease will contain both a detailed, discipline-specific coverage (paragraphs on medicinal chemistry, on clinical and preclinical characterization of compounds in development, on target identification and validation, on genetic factors influencing a pathology, etc.) and a drug discovery-oriented, overall evaluation of each target (validation, druggability, existing leads, etc.). Together these will satisfy the needs of various audiences, including in vitro biologists, pharmacologists, medicinal chemists, etc. Written to provide a comprehensive coverage of disease-modifying mechanisms and compounds against neurodegenerative diseases Provides a “drug discovery application oriented perspective, evaluating targets and candidates for their overall therapeutic potential Provides discipline-specific chapters (medicinal chemistry, target validation, preclinical and clinical development Provides an overview on a number of molecular mechanisms (e.g. phosphorylation, chaperon refolding, ubiquitination, autophagy, microtubule transportation, protease cleavage, etc.) with relevance for any disease area Contains a more thorough description of the therapeutic relevance of ~10 specific molecular targets

Research focused on protein folding, misfolding, and aggregation is leading to major advances across biochemistry and medicine. The elucidation of a folding code is proving to be of extreme importance in the postgenomic era, where a number of orphan genes have been identified for which no clear function has yet been established. This research is starting to shed light on the molecular and biochemical basis of a number of neurodegenerative diseases of dramatic impact. Protein Misfolding in Neurodegenerative Diseases: Mechanisms and Therapeutic Strategies addresses key issues concerning protein misfolding and aggregation in neurodegenerative diseases. Building on recent developments, including the recognition of protein misfolding as both a marker and a causal agent, the text presents the work of those who are actively pursuing more effective treatments, as well as preventative measures, and a possible cure. These include the use of molecular chaperones to control misfolding and novel pharmaceuticals, as well as the potential role of various inhibitors and NSAIDS. A Comprehensive Multifaceted Examination of the Complex Causal Agents Implicated in Protein Misfolding Divided into five sections, this groundbreaking text provides up-to-date accounts for Alzheimer’s, Parkinson’s, Huntington’s, Amyotrophic Lateral Sclerosis and Transmissible Spongiform Encephalitis. It also explores the highly likelihood that multiple factors, including oxidative stress, play a role in these complex diseases.

Protein misfolding and aggregation are hallmarks of several neurodegenerative proteinopathies. Though multiple factors like aging, oxidative stress, mitochondrial dysfunction, proteotoxic insults, genetic inconsistency, etc. are responsible for the dysfunction of the neuronal protein quality control system, targeting protein quality control has become an auspicious approach to halt the propagation of neurodegeneration. Quality Control of Cellular Protein in Neurodegenerative Disorders provides diverse aspects exploring the role of the protein quality control in neurodegenerative disorders and potential therapeutic strategies to combat the development and propagation of neurodegeneration. Featuring coverage on a broad range of topics such as molecular chaperones, protein misfolding, and stress signaling, this book is ideally designed for neurobiologists, neuropsychologists, neurophysiologists, medical professionals, neuropathologists, researchers, academicians, students, and practitioners engaged in studies of the protein quality control system in neuronal cells.

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”.

Neurodegenerative Diseases: New Insights for the Healthcare Professional: 2013 Edition is a ScholarlyEditions™ book that delivers timely, authoritative, and comprehensive information about Diagnosis and Screening. The editors have built Neurodegenerative Diseases: New Insights for the Healthcare Professional: 2013 Edition on the vast information databases of ScholarlyNews.™ You can expect the information about Diagnosis and Screening in this book to be deeper than what you can access anywhere else, as well as consistently reliable, authoritative, informed, and relevant. The content of Neurodegenerative Diseases: New Insights for the Healthcare Professional: 2013 Edition has been produced by the world’s leading scientists, engineers, analysts, research institutions, and companies. All of the content is from peer-reviewed sources, and all of it is written, assembled, and edited by the editors at ScholarlyEditions™ and available exclusively from us. You now have a source you can cite with authority, confidence, and credibility. More information is available at http://www.ScholarlyEditions.com/.

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.

This book will focus on synthesis, coating and functionalization chemistry of selected nanoparticles that are most commonly used in various biomedical applications. Apart from standard selected chemical synthetic methods, it focusses on design consideration of functionalization, selected coating chemistry for transforming as synthesized nanoparticle, selected conjugation chemistries and purification approach for such nanoparticles. It also includes state-of-art/future prospect of nanodrugs suitable for clinical applications. There will material on general application potential of these nanoparticles, importance of functionalization and common problems faced by non-chemists.