Chemical Modulators of Protein Misfolding and Neurodegenerative Disease

Chemical Modulators of Protein Misfolding and Neurodegenerative Disease PDF Author: Pierfausto Seneci
Publisher: Academic Press
ISBN: 012801959X
Category : Medical
Languages : en
Pages : 260

Get Book Here

Book Description
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

Chemical Modulators of Protein Misfolding and Neurodegenerative Disease

Chemical Modulators of Protein Misfolding and Neurodegenerative Disease PDF Author: Pierfausto Seneci
Publisher: Academic Press
ISBN: 012801959X
Category : Medical
Languages : en
Pages : 260

Get Book Here

Book Description
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

Molecular Targets in Protein Misfolding and Neurodegenerative Disease

Molecular Targets in Protein Misfolding and Neurodegenerative Disease PDF Author: Pierfausto Seneci
Publisher: Academic Press
ISBN: 0128004991
Category : Science
Languages : en
Pages : 314

Get Book Here

Book Description
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

Protein Misfolding in Neurodegenerative Diseases

Protein Misfolding in Neurodegenerative Diseases PDF Author: Robert D. E. Sewell
Publisher: CRC Press
ISBN: 1420007149
Category : Medical
Languages : en
Pages : 596

Get Book Here

Book Description
Current research suggests that neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, and Creutzfeldt-Jacob may be linked to disorders in protein shape referred to as protein misfolding. Continued study in this area could lead to promising advances in future treatment of these diseases. This groundbreaking text describes the latest findings regarding protein misfolding in the context of it being a marker, and perhaps a cause, in neurodegenerative diseases. Comprehensive coverage includes the diverse biochemical targets/markers for each disease, the currently limited success of drug therapies, and the cutting-edge research that could lead to more promising treatments.

Tau oligomers

Tau oligomers PDF Author: Jesus Avila
Publisher: Frontiers E-books
ISBN: 288919261X
Category : Medicine (General)
Languages : en
Pages : 114

Get Book Here

Book Description
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”.

Protein folding and misfolding: neurodegenerative diseases

Protein folding and misfolding: neurodegenerative diseases PDF Author: Judit Ovádi
Publisher: Springer Science & Business Media
ISBN: 1402094345
Category : Medical
Languages : en
Pages : 284

Get Book Here

Book Description
Offering all the latest in the study of neurodegenerative diseases, this book reviews the molecular events initiated by unfolded or misfolded proteins leading to conformational human diseases, especially those found in Parkinson’s and Alzheimer’s diseases.

Chemical Biology of Neurodegeneration

Chemical Biology of Neurodegeneration PDF Author: Pedro Merino
Publisher: John Wiley & Sons
ISBN: 3527344241
Category : Science
Languages : en
Pages : 378

Get Book Here

Book Description
Bridges the gap between the chemistry of small molecule neuromodulators and the complex pattern of neurodegenerative disorders Written by an experienced neurochemist, this book focuses on the main actors involved in neurodegenerative disorders at a molecular level, and places special emphasis on structural aspects and modes of action. Drawing on recent data on enzyme structure, mode of action, and inhibitor design, it describes?from a biochemical point of view?the six most important neurotransmitter systems and their constituent enzymes and receptors. Misfolding and aggregation of proteins within the brain is also covered. In addition, the book surveys a wide range of proven and prospective therapeutic agents that modulate key processes in the brain, from their chemical synthesis to their mode of action in model systems as well as in the patient. Chemical Biology of Neurodegeneration: A Molecular Approach is presented in two parts. The first introduces the neurotransmitter systems and provides a general explanation of the synapse and a description of the main structures involved in neurotransmission that can be considered therapeutic targets for disorders of the central nervous system. The second part presents molecular and chemical aspects directly involved or affected in neurodegeneration, including the metabolism of neurotransmitters, enzymes processing neurotransmitters, protein misfolding, and therapeutic agents. -Uses an interdisciplinary approach to bridge the gap between the basic biochemical events in a nerve cell and their neurological effects on the brain -Places emphasis on the chemistry of small molecule modulators that are potential lead molecules for new drugs -Covers six key neurotransmitter systems and their enzymes and receptors?dopaminergic, noradrenergic, serotonergic, cholinergic, GABAergic, and glutamatergic Chemical Biology of Neurodegeneration: A Molecular Approach is a key resource for medicinal chemists, neurobiologists, neurochemists, biochemists, molecular biologists, and neurophysiologists.

Investigating Neurodegenerative Diseases with Small Molecule Modulators

Investigating Neurodegenerative Diseases with Small Molecule Modulators PDF Author: Reka Rebecca Letso
Publisher:
ISBN:
Category :
Languages : en
Pages :

Get Book Here

Book Description
This was exemplified by a screen for small molecule inhibitors of cell death caused by a pathogenic, misofolded mutant huntingtin protein in a cell culture model of Huntington's Disease (HD). These cell death inhibitors were found to target protein disulfide isomerase (PDI), an oxidoreductase known to be important in endoplasmic reticulum quality control of protein folding. However, our studies utilizing the small molecule PDI inhibitors determined that the cell death observed in this system was due to a pro-apoptotic function of PDI involving proteins of the mitochondrial outer membrane. We have begun studies aimed at identifying the binding mode of these novel small molecule inhibitors of PDI, in efforts to develop more potent and efficacious analogs for testing in animal models of HD. These studies have helped defined a novel mechanism linking protein misfolding to cell death, and may prove to be relevant to a broader range of protein misfolding diseases.

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

Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging PDF Author: M. A. Hayat
Publisher: Academic Press
ISBN: 0128094273
Category : Medical
Languages : en
Pages : 431

Get Book Here

Book Description
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

Neurodegenerative Diseases

Neurodegenerative Diseases PDF Author: Uday Kishore
Publisher: BoD – Books on Demand
ISBN: 9535110888
Category : Medical
Languages : en
Pages : 642

Get Book Here

Book Description
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.

Bio-nanoimaging

Bio-nanoimaging PDF Author: Vladimir N Uversky
Publisher: Academic Press
ISBN: 0123978211
Category : Science
Languages : en
Pages : 556

Get Book Here

Book Description
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