Chemical Modulators of Protein Misfolding and Neurodegenerative Disease

Chemical Modulators of Protein Misfolding and Neurodegenerative Disease
Author: Pierfausto Seneci
Publisher: Academic Press
Total Pages: 260
Release: 2015-01-14
Genre: Medical
ISBN: 012801959X

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

Tau oligomers

Tau oligomers
Author: Jesus Avila
Publisher: Frontiers E-books
Total Pages: 114
Release: 2014-08-18
Genre: Medicine (General)
ISBN: 288919261X

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

Neurodegenerative Diseases
Author: Uday Kishore
Publisher: BoD – Books on Demand
Total Pages: 642
Release: 2013-05-15
Genre: Medical
ISBN: 9535110888

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.

Molecular Targets in Protein Misfolding and Neurodegenerative Disease

Molecular Targets in Protein Misfolding and Neurodegenerative Disease
Author: Pierfausto Seneci
Publisher: Academic Press
Total Pages: 314
Release: 2014-10-07
Genre: Science
ISBN: 0128004991

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

Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging

Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging
Author: M. A. Hayat
Publisher: Academic Press
Total Pages: 431
Release: 2016-12-28
Genre: Medical
ISBN: 0128094273

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

Bio-nanoimaging

Bio-nanoimaging
Author: Vladimir N Uversky
Publisher: Academic Press
Total Pages: 556
Release: 2013-11-05
Genre: Science
ISBN: 0123978211

Bio-Nanoimaging: Protein Misfolding & Aggregation provides a unique introduction to both novel and established nanoimaging techniques for visualization and characterization of misfolded and aggregated protein species. The book is divided into three sections covering: - Nanotechnology and nanoimaging technology, including cryoelectron microscopy of beta(2)-microglobulin, studying amyloidogensis by FRET; and scanning tunneling microscopy of protein deposits - Polymorphisms of protein misfolded and aggregated species, including fibrillar polymorphism, amyloid-like protofibrils, and insulin oligomers - Polymorphisms of misfolding and aggregation processes, including multiple pathways of lysozyme aggregation, misfolded intermediate of a PDZ domain, and micelle formation by human islet amyloid polypeptide Protein misfolding and aggregation is a fast-growing frontier in molecular medicine and protein chemistry. Related disorders include cataracts, arthritis, cystic fibrosis, late-onset diabetes mellitus, and numerous neurodegenerative diseases like Alzheimer's and Parkinson's. Nanoimaging technology has proved crucial in understanding protein-misfolding pathologies and in potential drug design aimed at the inhibition or reversal of protein aggregation. Using these technologies, researchers can monitor the aggregation process, visualize protein aggregates and analyze their properties. - Provides practical examples of nanoimaging research from leading molecular biology, cell biology, protein chemistry, biotechnology, genetics, and pharmaceutical labs - Includes over 200 color images to illustrate the power of various nanoimaging technologies - Focuses on nanoimaging techniques applied to protein misfolding and aggregation in molecular medicine

Quality Control of Cellular Protein in Neurodegenerative Disorders

Quality Control of Cellular Protein in Neurodegenerative Disorders
Author: Uddin, Md. Sahab
Publisher: IGI Global
Total Pages: 515
Release: 2020-02-14
Genre: Medical
ISBN: 1799813185

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.

Autophagosome and Phagosome

Autophagosome and Phagosome
Author: Vojo Deretic
Publisher: Humana Press
Total Pages: 455
Release: 2008-04-24
Genre: Science
ISBN: 9781588298539

Autophagy and phagocytosis are distinct yet partially morphologically similar processes. Understanding them is vital for the studies of cancer, aging, neurodegeneration, immunology, and infectious diseases. This book presents autophagosome and phagosome methods for novices and advanced researchers alike. Comprehensive and forward-thinking, the book offers a valuable guide to both cellular processes while inciting researchers to explore their potentially important connections.

Proteopathic Seeds and Neurodegenerative Diseases

Proteopathic Seeds and Neurodegenerative Diseases
Author: Mathias Jucker
Publisher: Springer Science & Business Media
Total Pages: 163
Release: 2013-03-27
Genre: Medical
ISBN: 3642354912

The misfolding and aggregation of specific proteins is an early and obligatory event in many of the age-related neurodegenerative diseases of humans. The initial cause of this pathogenic cascade and the means whereby disease spreads through the nervous system, remain uncertain. A recent surge of research, first instigated by pathologic similarities between prion disease and Alzheimer’s disease, increasingly implicates the conversion of disease-specific proteins into an aggregate-prone b-sheet-rich state as the prime mover of the neurodegenerative process. This prion-like corruptive protein templating or seeding now characterizes such clinically and etiologically diverse neurological disorders as Alzheimer ́s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and frontotemporal lobar degeneration. Understanding the misfolding, aggregation, trafficking and pathogenicity of the affected proteins could therefore reveal universal pathomechanistic principles for some of the most devastating and intractable human brain disorders. It is time to accept that the prion concept is no longer confined to prionoses but is a promising concept for the understanding and treatment of a remarkable variety of diseases that afflict primarily our aging society. ​

Biological Soft Matter

Biological Soft Matter
Author: Corinne Nardin
Publisher: John Wiley & Sons
Total Pages: 288
Release: 2021-04-06
Genre: Technology & Engineering
ISBN: 3527810994

Biological Soft Matter Explore a comprehensive, one-stop reference on biological soft matter written and edited by leading voices in the field Biological Soft Matter: Fundamentals, Properties and Applications delivers a unique and indispensable compilation of up-to-date knowledge and material on biological soft matter. The book presents a thorough overview about biological soft matter, beginning with different substance classes, including proteins, nucleic acids, lipids, and polysaccharides. It goes on to describe a variety of superstructures and aggregated and how they are formed by self-assembly processes like protein folding or crystallization. The distinguished editors have included materials with a special emphasis on macromolecular assembly, including how it applies to lipid membranes, and proteins fibrillization. Biological Soft Matter is a crucial resource for anyone working in the field, compiling information about all important substance classes and their respective roles in forming superstructures. The book is ideal for beginners and experts alike and makes the perfect guide for chemists, physicists, and life scientists with an interest in the area. Readers will also benefit from the inclusion of: An introduction to DNA nano-engineering and DNA-driven nanoparticle assembly Explorations of polysaccharides and glycoproteins, engineered biopolymers, and engineered hydrogels Discussions of macromolecular assemblies, including liquid membranes and small molecule inhibitors for amyloid aggregation A treatment of inorganic nanomaterials as promoters and inhibitors of amyloid fibril formation An examination of a wide variety of natural and artificial polymers Perfect for materials scientists, biochemists, polymer chemists, and protein chemists, Biological Soft Matter: Fundamentals, Properties and Applications will also earn a place in the libraries of biophysicists and physical chemists seeking a one-stop reference summarizing the rapidly evolving topic of biological soft matter.