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Protein Misfolding And Spreading Of Pathology In Neurodegenerative Diseases
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Book Synopsis The Molecular and Cellular Basis of Neurodegenerative Diseases by : Michael S. Wolfe
Download or read book The Molecular and Cellular Basis of Neurodegenerative Diseases written by Michael S. Wolfe and published by Academic Press. This book was released on 2018-03-29 with total page 561 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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
Download or read book Tau oligomers written by Jesus Avila and published by Frontiers E-books. This book was released on 2014-08-18 with total page 114 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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”.
Book Synopsis Neuropathology of Neurodegenerative Diseases by : Gabor G. Kovacs
Download or read book Neuropathology of Neurodegenerative Diseases written by Gabor G. Kovacs and published by Cambridge University Press. This book was released on 2017-12-13 with total page 320 pages. Available in PDF, EPUB and Kindle. Book excerpt: This practical guide to the diagnosis of neurodegenerative diseases discusses modern molecular techniques, morphological classification, fundamentals of clinical symptomology, diagnostic pitfalls and immunostaining protocols. It is based on the proteinopathy concept of neurodegenerative disease, which has influenced classification and provides new strategies for therapy. Numerous high-quality images, including histopathology photomicrographs and neuroradiology scans, accompany the description of morphologic alterations and interpretation of immunoreactivities. Diagnostic methods and criteria are placed within recent developments in neuropathology, including the now widespread application of immunohistochemistry. To aid daily practice, the guide includes diagnostic algorithms and offers personal insights from experienced experts in the field. Special focus is given to the way brain tissue should be handled during diagnosis. This is a must-have reference for medical specialists and specialist medical trainees in the fields of pathology, neuropathology and neurology working with neuropathologic features of neurodegenerative diseases.
Book Synopsis Etiology of Parkinson's Disease by : Jonas H. Ellenberg
Download or read book Etiology of Parkinson's Disease written by Jonas H. Ellenberg and published by CRC Press. This book was released on 1995-03-01 with total page 600 pages. Available in PDF, EPUB and Kindle. Book excerpt: This comprehensive reference provides a detailed overview of current concepts regarding the cause of Parkinson's disease-emphasizing the issues involved in the design, implementation, and analysis of epidemiological studies of parkinsonism.
Book Synopsis Leucine-Rich Repeat Kinase 2 (LRRK2) by : Hardy J. Rideout
Download or read book Leucine-Rich Repeat Kinase 2 (LRRK2) written by Hardy J. Rideout and published by Springer. This book was released on 2017-03-28 with total page 280 pages. Available in PDF, EPUB and Kindle. Book excerpt: This is the first book to assemble the leading researchers in the field of LRRK2 biology and neurology and provide a snapshot of the current state of knowledge, encompassing all major aspects of its function and dysfunction. The contributors are experts in cell biology and physiology, neurobiology, and medicinal chemistry, bringing a multidisciplinary perspective on the gene and its role in disease. The book covers the identification of LRRK2 as a major contributor to the pathogenesis of Parkinson's Disease. It also discusses the current state of the field after a decade of research, putative normal physiological roles of LRRK2, and the various pathways that have been identified in the search for the mechanism(s) of its induction of neurodegeneration.
Book Synopsis Dementia with Lewy Bodies by : John O'Brien
Download or read book Dementia with Lewy Bodies written by John O'Brien and published by CRC Press. This book was released on 2005-11-29 with total page 286 pages. Available in PDF, EPUB and Kindle. Book excerpt: Filling a noticeable gap in the market for a new text solely focused on Dementia with Lewy Bodies, this book discusses cutting-edge topics covering the condition from diagnosis to management, as well as what is known about the neurobiological changes involved. With huge progress having been made over the last decade in terms of the disorder
Book Synopsis Proteopathic Seeds and Neurodegenerative Diseases by : Mathias Jucker
Download or read book Proteopathic Seeds and Neurodegenerative Diseases written by Mathias Jucker and published by Springer Science & Business Media. This book was released on 2013-03-27 with total page 163 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Book Synopsis Neurodegenerative Diseases by : Uday Kishore
Download or read book Neurodegenerative Diseases written by Uday Kishore and published by BoD – Books on Demand. This book was released on 2013-05-15 with total page 642 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Book Synopsis Protein Misfolding and Spreading Pathology in Neurodegenerative Diseases by : Diana Fernandes Lázaro
Download or read book Protein Misfolding and Spreading Pathology in Neurodegenerative Diseases written by Diana Fernandes Lázaro and published by Frontiers Media SA. This book was released on 2020-02-20 with total page 158 pages. Available in PDF, EPUB and Kindle. Book excerpt: This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact.
Book Synopsis Neurodegenerative Diseases by : Shamim I. Ahmad
Download or read book Neurodegenerative Diseases written by Shamim I. Ahmad and published by Springer Science & Business Media. This book was released on 2012-03-12 with total page 421 pages. Available in PDF, EPUB and Kindle. Book excerpt: The editor of this volume, having research interests in the field of ROS production and the damage to cellular systems, has identified a number of enzymes showing ·OH scavenging activities details of which are anticipated to be published in the near future as confirmatory experiments are awaited. It is hoped that the information presented in this book on NDs will stimulate both expert and novice researchers in the field with excellent overviews of the current status of research and pointers to future research goals. Clinicians, nurses as well as families and caregivers should also benefit from the material presented in handling and treating their specialised cases. Also the insights gained should be valuable for further understanding of the diseases at molecular levels and should lead to development of new biomarkers, novel diagnostic tools and more effective therapeutic drugs to treat the clinical problems raised by these devastating diseases.
Book Synopsis Proteostasis and Disease by : Rosa Barrio
Download or read book Proteostasis and Disease written by Rosa Barrio and published by Springer Nature. This book was released on 2020-04-09 with total page 350 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book, written by members of the European network PROTEOSTASIS, provides an up-to-date review of the research regarding protein homeostasis in health and disease. With new discoveries contributing to the increasing complexity of this topic, the book offers a detailed overview of the pathways regulating protein homeostasis, including autophagy and the ubiquitin protein family. Following a basic introduction, it explains how defects in protein homeostasis contribute to numerous pathologies, including cancer, neurodegeneration, inflammation and a number of rare diseases. In addition, it discusses, the role of protein homeostasis in cellular development and physiology. Highlighting the latest research in the field of protein homeostasis and its implications for various clinically relevant diseases, the book appeals to researchers and clinicians, while also offering a reference guide for scholars who are new to the field.
Book Synopsis Bio-nanoimaging by : Vladimir N Uversky
Download or read book Bio-nanoimaging written by Vladimir N Uversky and published by Academic Press. This book was released on 2013-11-05 with total page 556 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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
Book Synopsis The Propagation of Neurodegenerative Diseases by Inflammation and Exosomes by : Valerie Sackmann
Download or read book The Propagation of Neurodegenerative Diseases by Inflammation and Exosomes written by Valerie Sackmann and published by Linköping University Electronic Press. This book was released on 2019-10-16 with total page 69 pages. Available in PDF, EPUB and Kindle. Book excerpt: Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the two most common neurodegenerative diseases with rates increasing along with the ageing global population. Despite best efforts, we still do not understand the etiopathogenesis of these diseases and there are no effective disease-modifying treatments. Cognitive deficiencies or motor complications that emerge during AD and PD are thought to be the result of the accumulation of misfolded, aggregate-prone proteins, such as amyloid-? (A?) and tau or ?-synuclein (?-syn), respectively. Growing evidence suggests that prefibrillar oligomers of A? and ?-syn (oA? and o?-syn) are key contributors to the progression of these diseases. The progressive accumulation of these proteins leads to a gradual spread of pathology throughout interconnected brain regions, but the mechanisms by which this spreading occurs are still largely unknown. Neuroinflammation has been recognised as an important contributor to neurodegenerative disease. It is hypothesised that a pro-inflammatory environment initiated by the innate immune system, either through activation from A? itself or indirectly through neuronal injury signals in AD. These phenomena are thought to either cause or accelerate AD, such that an anti-inflammatory approach may be neuroprotective. In paper I, we investigated whether different inflammatory environments affected the transfer of oA? between neuron-like cells, in addition to investigating inter- and intracellular protein changes. This study demonstrated that an anti-inflammatory environment reduces the transfer of oA? between cells. We also provide evidence that these cells begin to take on the “phenotype” of the inflammatory milieu, while also demonstrating that the expression profile of endosomal/lysosomal and protein trafficking proteins is altered during these conditions. Small extracellular vesicles called exosomes, which are key players in cell to cell communication, have been proposed to play an influential role in spreading neurodegenerative proteins between cells. Exosomes are small membranous vesicles that are formed by the inward budding of multivesicular bodies (MVBs). These MVBs can then merge with the plasma membrane to be released into the extracellular environment as vesicles, which serve as vehicles for transferring proteins, lipids, and mRNAs between cells. The ESCRT-dependent pathway is the most understood mechanism underlying exosome biogenesis. However, exosomes can also be formed through ESCRT-independent pathways, including through the hydrolysis of sphingomyelin by neutral sphingomyelinase 2 (nSMase2), which produces ceramide. Paper II investigated whether exosomes formed through an ESCRT-independent pathway plays a significant role in the transfer of o?-syn between neuron-like cells. As oxidative stress is a common feature in PD brains, which in turn dysregulates nSMase2 activity, we also tested our model under hypoxic conditions. Inhibition of nSMase2 significantly reduced the transfer of o?-syn between cells but also resulted in decreased ?-syn aggregation. Hypoxia did not influence o?-syn transfer, however, it significantly dysregulated the sphingolipid composition, which may be important for ?-syn binding to exosomes and exosome communication. During AD and PD, there is a noted reduction in the effectiveness of autophagy, a process critical to cellular proteostasis. Recent studies have uncovered shared regulatory mechanisms of exosome biogenesis and autophagy, suggesting that they are closely linked. Previous findings have shown that inhibition of autophagy in AD mice mediates A? trafficking through altering the secretion of A? in MVBs. To further study this effect, we investigated the interplay between autophagy and exosome secretion using ATG7 knock-out x APPNL-F knock-in AD mice in paper III. These autophagy-deficient AD mice had a reduced extracellular A? plaque load, but increased intracellular A?, which was found to be assembled into higher-ordered assemblies. While exosomal secretion was dysregulated in these mice, the amount of A? packaged into the exosomes was unchanged. Lastly, one of the biggest challenges in developing effective treatments for AD is the lack of early diagnosis of living patients. As the connection between exosomes and the spread of neurodegenerative proteins is still relatively new, there remains a diagnostic potential to be explored with exosomes. Paper IV aimed to develop a new diagnostic assay to detect oA? in exosomes isolated from human cerebrospinal fluid. Although exosomal oA? was readily detected in some of these samples, the assay’s sensitivity requires additional optimisation before it can be further validated for the clinic. In summary, the studies presented in this thesis have furthered our understanding of how inflammation, autophagy, and exosomes contribute to the intercellular transmission of AD and PD associated proteins. We have shown that an anti-inflammatory approach may slow down the progression of AD through reducing the transfer of oA? between cells. We also provide novel findings relating to the biogenesis of exosomes, which in turn affected the ability of exosomes to transmit neurodegenerative proteins between cells, and their association with autophagic processes. Finally, we have investigated the feasibility of exosomes as an early AD diagnostic marker. This work has helped to elucidate some of the mechanisms underlying the progression of neurodegenerative diseases, which may be useful targets for the investigation of new therapeutic avenues.
Book Synopsis Alzheimer's Disease by : Thimmaiah Govindaraju
Download or read book Alzheimer's Disease written by Thimmaiah Govindaraju and published by Royal Society of Chemistry. This book was released on 2022-01-04 with total page 531 pages. Available in PDF, EPUB and Kindle. Book excerpt: Alzheimer’s disease is an increasingly common form of dementia and despite rising interest in discovery of novel treatments and investigation into aetiology, there are no currently approved treatments that directly tackle the causes of the condition. Due to its multifactorial pathogenesis, current treatments are directed against symptoms and even precise diagnosis remains difficult as the majority of cases are diagnosed symptomatically and usually confirmed only by autopsy. Alzheimer’s Disease: Recent Findings in Pathophysiology, Diagnostic and Therapeutic Modalities provides a comprehensive overview from aetiology and neurochemistry to diagnosis, evaluation and management of Alzheimer's disease, and latest therapeutic approaches. Intended to provide an introduction to all aspects of the disease and latest developments, this book is ideal for students, postgraduates and researchers in neurochemistry, neurological drug discovery and Alzheimer’s disease.
Book Synopsis Neurodegenerative Diseases by : G. Jolles
Download or read book Neurodegenerative Diseases written by G. Jolles and published by Academic Press. This book was released on 1994-11-14 with total page 330 pages. Available in PDF, EPUB and Kindle. Book excerpt: Over the last few years, the considerable progress made in biochemistry, virology, molecular biology and genetics has revealed some of the intimate mechanisms of the neurodegenerative diseases. The present volume is an attempt to review the latest data in the field to illuminate new avenues for future research. This volume gathers together chapters and discussions on the etiology and pathogenesis of the neurodegenerative diseases. Apoptosis of programmed cell death as well as other genetic implications are discussed; special attention is given to the coexistence and interconnection of genetic and environmental factors. There is extensive coverage of prions responsible for bovine spongiform encephalopathy, Cruetzfeld-Jacob disease and kuru. The various aspects of non-conventional transmissible agents are thoroughly reviewed. Further contributions deal with the role of growth factors as well as of free radicals. Consideration is given to the molecular mechanisms of Alzheimer's disease, in particular the role of tau protein. Finally, several pharmacological models now available, which throw light upon aspects of Parkinson's disease, Huntington's chorea and multiple sclerosis, are examined and discussed. It is hoped that recent scientific advances will lead to the discovery of new drugs to fill the current therapeutic void. There are hopes of an early indication of this in the case of amyotrophic lateral sclerosis.
Book Synopsis Molecular Chaperones in Health and Disease by : Matthias Gaestel
Download or read book Molecular Chaperones in Health and Disease written by Matthias Gaestel and published by Springer Science & Business Media. This book was released on 2005-09-27 with total page 464 pages. Available in PDF, EPUB and Kindle. Book excerpt: Molecular chaperones are involved in a wide variety of essential cellular processes in living cells. A subset of molecular chaperones have been initially described as heat shock proteins protecting cells from stress damage by keeping cellular proteins in a folding competent state and preventing them from irreversible aggregation. Later it became obvious that molecular chaperones are also expressed constitutively in the cell and are involved in complex processes such as protein synthesis, intracellular protein transport, post-translational modification and secretion of proteins as well as receptor signalling. Hence, it is not surprising that molecular chaperones are implicated in the pathogenesis of many relevant diseases and could be regarded as potential pharmacological targets. Starting with the analysis of the mode of action of chaperones at the molecular, cellular and organismic level, this book will then describe specific aspects where modulation of chaperone action could be of pharmacological and therapeutic interest.
Book Synopsis Neurodegeneration and Alzheimer's Disease by : Ralph N. Martins
Download or read book Neurodegeneration and Alzheimer's Disease written by Ralph N. Martins and published by John Wiley & Sons. This book was released on 2019-07-10 with total page 548 pages. Available in PDF, EPUB and Kindle. Book excerpt: Understanding the impact of diet, exercise, genetics, and hormones on the risk and development of Alzheimer’s and other neurogenerative diseases Diet is widely known to impact on neurological function. Nevertheless, academic texts discussing this relationship are relatively few in number. This book therefore fills an important gap in the current literature. Opening with an overview of neurodegenerative diseases, particularly Alzheimer’s disease, the text then focuses on explaining the means by which glycemic control and lipid metabolism – and associated nutritional and lifestyle variables – may factor into such disorders’ prevention and treatment. An international group of experts in the fields of food science and neurodegeneration have contributed chapters that examine Alzheimer’s disease within a broad range of contexts. Offering dietary, genetic, and hormonal perspectives, the authors explore topics ranging from sugar consumption to digestive fermentation, and Alzheimer’s disease animal models to the cognition-enhancing effects of physical exercise. Also included are overviews of the latest research into current and developing methods of treatment and diagnosis, as well as differential diagnostics. This groundbreaking book: Explores how glucose metabolism, insulin resistance, lipid metabolism, and high intake of refined carbohydrates are linked to Alzheimer's disease Discusses how genetic makeup can impact risk of Alzheimer’s and Parkinson’s disease Examines cognitive changes in neurodegeneration, lists current tests for determining cognitive impairment, and provides information concerning differential diagnosis Discusses potential advantages of increasing antioxidant and micronutrient intake Reviews hormonal influences on neurodegeneration Examines the links between protein intake and Alzheimer’s disease. Neurodegeneration and Alzheimer's Disease is an essential resource for researchers, medical practitioners, dietitians, and students with an interest in neurological diseases and their diagnosis and risk factors, as well as diet-related conditions such as diabetes and obesity. Lifestyle and diet influence neurodegeneration risk, and a better understanding of this evidence amongst health professionals will hopefully lead to greater public awareness of how to reduce the likelihood of these widespread conditions.
