Download or read book Structural and Biochemical Studies of Patient extracted Amyloid Fibrils written by Yi Xiao Jiang and published by . This book was released on 2023 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Human neurodegenerative diseases cause the gradual loss of neurons and progressive decline in memory, cognitive ability, movement and behavior. These devastating conditions afflict millions of patients worldwide and their families, however the molecular mechanisms of pathogenesis are not well understood, resulting in the lack of effective treatments and early diagnostic tools. Gross analyses of post-mortem brains using immunohistochemistry has identified abnormal deposits of amyloid proteins as defining features of neurodegenerative diseases. Amyloid proteins, like prions, can template aggregation of monomers into highly ordered, stable fibrils composed of tightly interdigitating [Beta]-sheets. Recent advances in cryogenic-electron microscopy (cryo-EM) have enabled the structural determination of amyloid fibrils to near-atomic resolution. These structures provide insight into the formation and propagation of amyloid fibrils, and can guide the design of therapies that prevent, delay, or reverse the aggregation of proteins in neurodegenerative diseases. Moreover, previous work has shown that the structures of brain-extracted fibrils differ from the structures of fibrils assembled in vitro, underscoring the importance of studying patient-derived samples. In my thesis research, I extracted amyloid fibrils from autopsied brains of patients with frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) and determined their structures using cryo-EM. Surprisingly, the fibrils examined were not formed by TDP-43 but by a fragment of transmembrane protein 106B (TMEM106B), revealing a previously unsuspected amyloid protein. In addition, I used a biosensor cell line, which detects proteopathic TDP-43 aggregates from sarkosyl-insoluble brains extracts, to study cohorts of TDP-43 proteinopathy cases including amyotrophic lateral sclerosis (ALS), FTLD-TDP and Alzheimer's disease (AD). My work expands the insight into the molecular basis of amyloid disorders, and inspires future research to address newly raised questions about TMEM106B and TDP-43 in neurodegenerative diseases.
Download or read book Amyloid Proteins written by Einar M. Sigurdsson and published by Springer Science & Business Media. This book was released on 2008-02-02 with total page 390 pages. Available in PDF, EPUB and Kindle. Book excerpt: A proven collection of readily reproducible techniques for studying amyloid proteins and their involvement in the etiology, pathogenesis, diagnosis, and therapy of amyloid diseases. The contributors provide methods for the preparation of amyloid and its precursors (oligomers and protofibrils), in vitro assays and analytical techniques for their study, and cell culture models and assays for the production of amyloid proteins. Additional chapters present readily reproducible techniques for amyloid extraction from tissue, its detection in vitro and in vivo, as well as nontransgenic methods for developing amyloid mouse models. The protocols follow the successful Methods in Molecular BiologyTM series format, each offering step-by-step laboratory instructions, an introduction outlining the principle behind the technique, lists of the necessary equipment and reagents, and tips on troubleshooting and avoiding known pitfalls.
Download or read book The Hippocampus Book written by Per Andersen and published by Oxford University Press. This book was released on 2007 with total page 892 pages. Available in PDF, EPUB and Kindle. Book excerpt: The hippocampus is one of a group of remarkable structures embedded within the brain's medial temporal lobe. Long known to be important for memory, it has been a prime focus of neuroscience research for many years. The Hippocampus Book promises to facilitate developments in the field in a major way by bringing together, for the first time, contributions by leading international scientists knowledgeable about hippocampal anatomy, physiology, and function. This authoritative volume offers the most comprehensive, up-to-date account of what the hippocampus does, how it does it, and what happens when things go wrong. At the same time, it illustrates how research focusing on this single brain structure has revealed principles of wider generality for the whole brain in relation to anatomical connectivity, synaptic plasticity, cognition and behavior, and computational algorithms. Well-organized in its presentation of both theory and experimental data, this peerless work vividly illustrates the astonishing progress that has been made in unraveling the workings of the brain. The Hippocampus Book is destined to take a central place on every neuroscientist's bookshelf.
Download or read book The Biology of Alzheimer Disease written by Dennis J. Selkoe and published by Cold Spring Harbor Perspective. This book was released on 2012 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Alzheimer disease causes the gradual deterioration of cognitive function, including severe memory loss and impairments in abstraction and reasoning. Understanding the complex changes that occur in the brain as the disease progressesincluding the accumulation of amyloid plaques and neurofibrillary tanglesis critical for the development of successful therapeutic approaches. Written and edited by leading experts in the field, this collection from Cold Spring Harbor Perspectives in Medicine includes contributions covering all aspects of Alzheimer disease, from our current molecular understanding to therapeutic agents that could be used to treat and, ultimately, prevent it. Contributors discuss the biochemistry and cell biology of amyloid -protein precursor (APP), tau, presenilin, -secretase, and apolipoprotein E and their involvement in Alzheimer disease. They also review the clinical, neuropathological, imaging, and biomarker phenotypes of the disease; genetic alterations associated with the disorder; and epidemiological insights into its causation and pathogenesis. This comprehensive volume, which includes discussions of therapeutic strategies that are currently used or under development, is a vital reference for neurobiologists, cell biologists, pathologists, and other scientists pursuing the biological basis of Alzheimer disease, as well as investigators, clinicians, and students interested in its pathogenesis, treatment, and prevention.
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”.
Download or read book Pathobiology of Alzheimer s Disease written by and published by Elsevier. This book was released on 1995-10-17 with total page 273 pages. Available in PDF, EPUB and Kindle. Book excerpt: Neuroscience Perspectives provides multidisciplinary reviews of topics in one of the most diverse and rapidly advancing fields in the life sciences.Whether you are a new recruit to neuroscience, or an established expert, look to this series for 'one-stop' sources of the historical, physiological, pharmacological, biochemical, molecular biological and therapeutic aspects of chosen research areas.The last decade has seen tremendous advances in our understanding of the pathobiology of Alzheimer's disease. These will lead to the first generation of drugs aimed at prevention rather than cure. This book covers some of the most important and exciting of these advances, with chapters written by many of the leading researchers in the field.With genetic studies as a backbone to this volume many chapters are devoted to the function and regulation of amyloid b-protein precursor (APP) and apolipoprotein E (ApoE). Other chapters describe cell biological approaches helping to piece together the link between the genetic alterations and the phenotype we call Alzheimer's disease.Although APP and its proteolytic cleavage product, amyloid b-protein, do not answer all the questions, detailed research into this system has undoubtedly increased our knowledge of the pathobiology of AD and has lead to the identification of other risk factors. Understanding the role of ApoE in the pathology of Alzheimer's disease promises to open a whole new field in AD research. * * Reviews the current knowledge of the pathogenesis of Alzheimer's Disease from a clinical perspective to a genetic and cell biological perspective* A comprehensive description of the role of amyloid B-protein precursor in Alzheimer's disease.* Up-to-date research data* Clear illustrations complement the text
Download or read book Glutamine Repeats and Neurodegenerative Diseases written by Peter S. Harper and published by Oxford University Press, USA. This book was released on 2001 with total page 352 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book focuses on the discovery of a common genetic basis for a group of inherited neurological disorders, including Huntington's Disease, spino-bulbar atrophy and a series of hereditary ataxias. This shared molecular background and other similarities have led to the development of theoretical models for the pathogenesis of these diseases. It is now also clear that the mechanisms involved are likely to be of more general relevance, outside of this particular group of disorders, with implications for other neurodegenerative processes such as those involved in Alzheimer's, Parkinson's and Prion diseases. The book is an edited and updated compilation evolving from a Royal Society discussion meeting.
Download or read book Alzheimer s Disease Cellular and Molecular Aspects of Amyloid beta written by J. Robin Harris and published by Springer Science & Business Media. This book was released on 2006-11-22 with total page 416 pages. Available in PDF, EPUB and Kindle. Book excerpt: To understand Alzheimer's disease (AD) is one of the major thrusts of present-day clinical research, strongly supported by more fimdamental cellular, biochemical, immunological and structural studies. It is these latter that receive attention within this book. This compilation of 20 chapters indicates the diversity of work currently in progress and summarizes the current state of knowledge. Experienced authors who are scientifically active in their fields of study have been selected as contributors to this book, in an attempt to present a reasonably complete survey of the field. Inevitably, some exciting topics for one reason or another have not been included, for which we can only apologize. Standardization of terminology is often a problem in science, not least in the Alzheimer field; editorial effort has been made to achieve standardization between the Chapters, but some minor yet acceptable personal / author variation is still present, i. e. P-amyloid/amyloid-P; Ap42/Apl-42/APi. 42! The book commences with a broad survey of the contribution that the range of available microscopical techniques has made to the study of Alzheimer's amyloid plaques and amyloid fibrillogenesis. This chapter also serves as an Introduction to the book, since several of the topics introduced here are expanded upon in later chapters. Also, it is significant to the presence of this chapter that the initial discovery of brain plaques, by Alois Alzheimer, utilized light microscopy, a technique that continues to be extremely valuable in present-day AD research.
Download or read book The Biochemistry of Amyloids in Neurodegenerative Diseases Volume I written by Cláudio M. Gomes and published by Frontiers Media SA. This book was released on 2022-02-02 with total page 153 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book The biochemistry of amyloids in neurodegenerative diseases volume II written by Cláudio M. Gomes and published by Frontiers Media SA. This book was released on 2023-07-19 with total page 193 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Physical Biology of Proteins and Peptides written by Luis Olivares-Quiroz and published by Springer. This book was released on 2015-10-22 with total page 184 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book covers the latest developments in the physical biology of proteins and peptides. Key insights into microscopic and macroscopic approaches to describe biologically relevant macromolecules and their interactions are provided. This book also covers a wide range of tools, including theoretical methods as statistical mechanics, normal mode analysis, kinetic theory and stochastic processes, and all-atom and coarse-grained molecular dynamics simulations. New experimental techniques are also discussed, particularly related to amiloidogenic peptides and their mutations. This is an excellent book for molecular biologists, physicists, computational scientists, and chemists. It covers cutting-edge research in this exciting, interdisciplinary research field. This book also: Discusses the latest developments in the physical biology of proteins, peptides and enzymes covering theoretical, computational, and experimental approaches Broadens readers’ understanding on the r ole of intra- and inter-molecular interactions as a fundamental cornerstone of macroscopic biological properties of macromolecules Provides a wide and useful perspective on different aspects of the physics, biology, and chemistry of proteins and peptides suitable for interdisciplinary research.
Download or read book Biological Soft Matter written by Corinne Nardin and published by John Wiley & Sons. This book was released on 2021-04-06 with total page 288 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Amyloid Fibrils and Prefibrillar Aggregates written by Daniel Erik Otzen and published by John Wiley & Sons. This book was released on 2013-06-04 with total page 496 pages. Available in PDF, EPUB and Kindle. Book excerpt: Summing up almost a decade of biomedical research, this topical and eagerly awaited handbook is the first reference on the topic to incorporate recent breakthroughs in amyloid research. The first part covers the structural biology of amyloid fibrils and pre-fibrillar assemblies, including a description of current models for amyloid formation. The second part looks at the diagnosis and biomedical study of amyloid in humans and in animal models, while the final section discusses pharmacological approaches to manipulating amyloid and also looks at its physiological roles in lower and higher organisms. For Biochemists, Molecular Biologists, Neurobiologists, Neurophysiologists and those working in the Pharmaceutical Industry.
Download or read book Amyloid and Amyloidosis 1990 written by Jacob B Natvig and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 959 pages. Available in PDF, EPUB and Kindle. Book excerpt: Both scientifically and socially the Vlth International Symposium on Amyloidosis, August 5 - 8, 1990 in Oslo was a great success. There were three and a half intensive days. It started with the Opening Ceremony, particularly highlighted with the Norway-Norway multi media show by David Cochron, and ended with a visit to the Edvard Munch museuro and the Farewell Salmon Dinner on the evening of August 8 (not to forget the "happy birthday" song for Dorothea Zucker-Franklin at the breakfast table the following morning). In between was the intellectual penetration into the science of amyloidosis and amyloid proteins, and a deepening of many friendships among young and old "amyloidologists", together with some of the cultural and historical features of Oslo and Norway. Among the numerous Ietters of thanks and gratitude that we have received, the senior organizer of the previous meeting, Takashi lsobe said it briefly and eloquently: "You have overwhelmed us, you have performed a drama with joy and cheer, you have hosted so nicely with lovely secretariat, you have arranged impressive hospitality in every respect, you certainly did for all of us" Now we are left with the proceedings book for the three coming years until the next symposium in Kingston, Canada, which will be organized by Drs. Robert Kisilevsky and Thomas Muckle from the Department of Pathology at Queens University in 1993. The scientific contributions herein cover all the sessions of the meeting.
Download or read book Prion written by Yusuf Tutar and published by BoD – Books on Demand. This book was released on 2017-03-08 with total page 240 pages. Available in PDF, EPUB and Kindle. Book excerpt: Protein aggregation causes malfunction in several biochemical processes. Genetic and spontaneous formations of these transmissible spongiform encephalopathies are fatal to humans and animals. Conformational change of normal form of the protein to misfolded form causes its accumulation. The misfolded infectious protein agent forms the pathogenesis of the disease. This book presents pathology of the disease along with current knowledge of the structure-activity mechanism in the first two sections. Dyshomeostasis of metals is implicated in the pathogenesis of prions, and this influence is discussed further to understand the prion mechanism. Genetic resistance and immunobiology of the disease are elaborated in the following section. Finally, a computational study on the dynamics of the prion propagation provides a structural basis of the mechanism.
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
Download or read book Recent Advances in Transthyretin Evolution Structure and Biological Functions written by Samantha J. Richardson and published by Springer Science & Business Media. This book was released on 2009-08-09 with total page 367 pages. Available in PDF, EPUB and Kindle. Book excerpt: Since its ?rst description in 1942 in both serum and cerebrospinal ?uid, transthyretin (TTR) has had an eventful history, including changes in name from “prealbumin” to “thyroxine-binding prealbumin” to “transthyretin” as knowledge increased about its functions. TTR is synthesised in a wide range of tissues in humans and other eutherian mammals: the liver, choroid plexus (blood- cerebrospinal ?uid barrier), retinal pigment epithelium of the eye, pancreas, intestine and meninges. However, its sites of synthesis are more restricted in other vertebrates. This implies that the number of tissues synthesising TTR during vertebrate evolution has increased, and raises questions about the selection pressures governing TTR synthesis. TTR is most widely known as a distributor of thyroid hormones. In addition, TTR binds retinol-binding protein, which binds retinol. In this way, TTR is also involved with retinoid distribution. More recently, TTR has been demonstrated to bind a wide variety of endocrine disruptors including drugs, pollutants, industrial compounds, heavy metals, and some naturally occurring plant ?avonoids. These not only interfere with thyroid hormone delivery in the body, but also transport such endocrine disruptors into the brain, where they have the potential to accumulate.
