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Protein Degradation Aggregation Membrane Trafficking And Exosomes In Neuronal Health And Disease
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Book Synopsis Protein Degradation, Aggregation, Membrane Trafficking and Exosomes in Neuronal Health and Disease by : Beatriz Alvarez
Download or read book Protein Degradation, Aggregation, Membrane Trafficking and Exosomes in Neuronal Health and Disease written by Beatriz Alvarez and published by Frontiers Media SA. This book was released on 2022-08-02 with total page 155 pages. Available in PDF, EPUB and Kindle. Book excerpt:
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 60 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 Mesenchymal Stem Cell Derived Exosomes by : Yaoliang Tang
Download or read book Mesenchymal Stem Cell Derived Exosomes written by Yaoliang Tang and published by Academic Press. This book was released on 2015-09-02 with total page 287 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mesenchymal stem cell-derived exosomes are at the forefront of research in two of the most high profile and funded scientific areas – cardiovascular research and stem cells. Mesenchymal Stem Cell Derived Exosomes provides insight into the biofunction and molecular mechanisms, practical tools for research, and a look toward the clinical applications of this exciting phenomenon which is emerging as an effective diagnostic. Primarily focused on the cardiovascular applications where there have been the greatest advancements toward the clinic, this is the first compendium for clinical and biomedical researchers who are interested in integrating MSC-derived exosomes as a diagnostic and therapeutic tool. - Introduces the MSC-exosome mediated cell-cell communication - Covers the major functional benefits in current MSC-derived exosome studies - Discusses strategies for the use of MSC-derived exosomes in cardiovascular therapies
Book Synopsis Exosomes in Cardiovascular Diseases by : Junjie Xiao
Download or read book Exosomes in Cardiovascular Diseases written by Junjie Xiao and published by Springer. This book was released on 2017-09-19 with total page 300 pages. Available in PDF, EPUB and Kindle. Book excerpt: The book provides and intensive overview on exosomes in cardiovascular diseases, its potential as biomarkers, as well as pathological and therapeutic effects. It firstly describes the general aspects of exosomes including the definition, formation and secretion of exosomes and highlight their roles as biomarkers and pathological and therapeutic effects in cardiovascular diseases as well. Secondly, basic aspects of exosomes including the purification methods of exosomes, exosomes content, and functional roles of the cardiovascular exosomes are summarized. Thirdly, exosomes as biomarkers of cardiovascular diseases are overviewed including their roles in diagnosis, prognosis and reaction to therapy. Fourthly, pathological effects of exosomes and therapeutic effects of exosomes are highlighted. Finally, future prospects of exosomes in cardiovascular research would be provided. This is an essential reference for researchers working in cell biology and regeneration, as well as clinicians such as cardiologist.
Book Synopsis Dopamine Handbook by : Leslie L. Iversen
Download or read book Dopamine Handbook written by Leslie L. Iversen and published by . This book was released on 2010 with total page 632 pages. Available in PDF, EPUB and Kindle. Book excerpt: The discovery of dopamine in 1957-1958 was one of the seminal events in the development of modern neuroscience, and has been extremely important for the development of modern therapies of neurological and psychiatric disorders. Dopamine has a fundamental role in almost all aspects of behavior: from motor control to mood regulation, cognition and addiction and reward, and dopamine research has been unique within the neurosciences in the way it has bridged basic science and clinical practice. Over the decades research into the role of dopamine in health and disease has been in the forefront of modern neuroscience. The Dopamine Handbook is the first single-volume publication to capture current progress and excitement in this dynamic research field.
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 Neuroanatomy and Pathology of Sporadic Parkinson's Disease by : Heiko Braak
Download or read book Neuroanatomy and Pathology of Sporadic Parkinson's Disease written by Heiko Braak and published by Springer. This book was released on 2008-12-03 with total page 119 pages. Available in PDF, EPUB and Kindle. Book excerpt: The synucleinopathy sporadic Parkinson’s disease (sPD) is the second most frequent degenerative disorder of the human nervous system after Alzheimer’s disease. The propensity for developing sPD exists in all ethnic groups worldwide, and the prevalence of the disorder increases considerably with age, thereby imposing an enormous social and economic burden on societies with increased life expectancy. The sPD-associated pathological process is progressive, does not go into remission, and can take decades to reach its culmination if it is not be terminated prematurely by death owing to other causes. Against the background of the normal morphology and anatomy, the authors analyze the pathoanatomy of sPD in the nervous system at various neuropathological stages and summarize the potential functional consequences of the lesions.
Book Synopsis Trafficking Inside Cells by : Nava Segev
Download or read book Trafficking Inside Cells written by Nava Segev and published by Springer Science & Business Media. This book was released on 2010-05-30 with total page 459 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book covers the past, present and future of the intra-cellular trafficking field, which has made a quantum leap in the last few decades. It details how the field has developed and evolved as well as examines future directions.
Book Synopsis Exosomes and Microvesicles by : Andrew F Hill
Download or read book Exosomes and Microvesicles written by Andrew F Hill and published by Humana. This book was released on 2016-12-10 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume covers methods for the analysis of extracellular vesicles (EV) that can be applied to isolated EVs from a wide variety of sources. This includes the use of electron microscopy, tunable resistance pulse sensing, and nanoparticle tracking analysis. The chapters in this book discuss EV cargoes containing proteins and genomic materials using a number of different approaches, and isolating EVs from platelets and neuronal cells and tissues. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Practical and comprehensive, Exosomes and Microvesicles: Methods and Protocols is a valuable resource containing methodologies for anyone interested in researching EVs.
Book Synopsis Extracellular Vesicles in Health and Disease by : Paul Harrison
Download or read book Extracellular Vesicles in Health and Disease written by Paul Harrison and published by CRC Press. This book was released on 2014-05-02 with total page 484 pages. Available in PDF, EPUB and Kindle. Book excerpt: Interest in the role of extracellular vesicles (microvesicles and exosomes) is expanding rapidly. It is now apparent that far from being merely cellular debris, these vesicles play a key role in cell-to-cell communication and signaling. Moreover, they are significantly elevated in a number of diseases. This raises the question of their direct role in pathogenesis as well as their possible use as biomarkers. This book stems from the first international meeting on "Microvesicles and Nanovesicles in Health and Disease" held at Magdalen College, Oxford, in 2010. The purpose of the meeting was to bring together, for the first time, a range of experts from around the world to discuss the latest advances in this field. Key to the study of these vesicles is the availability of methodologies for their measurement in biological fluids. A major section of the meeting focused on a range of exciting new technologies which have been developed for this purpose. The presentations at this meeting form the basis of this book, which will appeal to basic scientists, clinicians, and those developing technology for the measurement of extracellular vesicles.
Book Synopsis Exosomes in Brain Health and Disease by : Konstantin Glebov
Download or read book Exosomes in Brain Health and Disease written by Konstantin Glebov and published by Frontiers Media SA. This book was released on 2022-06-06 with total page 267 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Ubiquitin Proteasome System by : Matthew Summers
Download or read book Ubiquitin Proteasome System written by Matthew Summers and published by BoD – Books on Demand. This book was released on 2019-06-19 with total page 228 pages. Available in PDF, EPUB and Kindle. Book excerpt: The human ubiquitin proteasome system (UPS) is comprised of nearly 1000 proteins. Although originally identified as a mechanism of protein destruction, the UPS has numerous additional functions and mediates central signaling events in myriad processes involved in both cellular and organismal health and homeostasis. Numerous pathways within the UPS are implicated in disease, ranging from cancer to neurodegenerative diseases such as Parkinson's. The goal of this book is to deliver a collection of synopses of current areas of UPS research that highlights the importance of understanding the biology of the UPS to identify disease-relevant pathways, and the need to elucidate the molecular machinations within the UPS to develop methods for therapeutic modulation of these pathways.
Book Synopsis Membrane Biogenesis by : Jos A.F. Op den Kamp
Download or read book Membrane Biogenesis written by Jos A.F. Op den Kamp and published by Springer Science & Business Media. This book was released on 2013-06-29 with total page 474 pages. Available in PDF, EPUB and Kindle. Book excerpt: Many individual aspects of the dynamics and assembly of biological membranes have been studied in great detail. Cell biological approaches, advanced genetics, biophysics and biochemistry have greatly contributed to an increase in our knowledge in this field.lt is obvious however, that the three major membrane constituents - lipids, proteins and carbohydrates- are studied, in most cases separately and that a coherent overview of the various aspects of membrane biogenesis is not readily available. The NATO Advanced Study Institute on "New Perspectives in the Dynamics of Assembly of Biomembranes" intended to provide such an overview: it was set up to teach students and specialists the achievements obtained in the various research areas and to try and integrate the numerous aspects of membrane assembly into a coherent framework. The articles in here reflect this. Statting with detailed contributions on phospholipid structure, dynamics, organization and biogenesis, an up to date overview of the basic, lipidic backbone of biomembranes is given. Extensive progress is made in the research on membrane protein biosynthesis. In particular the post- and co-translational modification processes of proteins, the mechanisms of protein translocation and the sorting mechanisms which are necessary to direct proteins to their final, intra - or extracellular destination have been characterized in detail. Modern genetic approaches were indispensable in this research area: gene cloning, hybrid protein construction, site directed mutagenesis and sequencing techniques elucidated many functional aspects of specific nucleic acid and amino acid sequences.
Download or read book The Prion Protein written by Jorg Tatzelt and published by . This book was released on 2010 with total page 80 pages. Available in PDF, EPUB and Kindle. Book excerpt: A conformational transition of the cellular prion protein (PrPC) into an aberrantly folded isoform designated scrapie prion protein (PrPSc) is the hallmark of a variety of neurodegenerative disorders collectively called prion diseases. They include Creutzfeldt-Jakob disease and Gerstmann-Stäussler-Scheinker syndrome in humans, scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle and chronic wasting disease (CWD) in free-ranging deer. In contrast to the deadly properties of misfolded PrP, PrPC seems to possess a neuroprotective activity. More-over, animal models indicated that the stress-protective activity of PrPC and the neurotoxic effects of PrPSc are somehow interconnected. In this timely book, leading scientists in the field have come together to highlight the apparently incongruous activities of different PrP conformers. The articles outline current research on celluar pathways implicated in the formation and signaling of neurotoxic and physiological PrP isoforms and delineate future research direction. Topics covered include the physiologcial activity of PrPC and its possible role as a neurotrophic factor, the finding that aberrant PrP conformers can cause neurodegeneration in the absence of infectious prion propagation, the requirement of the GPI anchor of PrPC for the neurotoxic effects of scrapie prions, the pathways implicated in the formation and neurotoxic properties of cytosolically localized PrP, the impact of metal ions on the processing of PrP, and the role of autophagy in the propagation and clearance of PrPSc. The book is fully illustrated and chapters include comprehensive reference sections. Essential reading for scientists involved in prion research.
Book Synopsis Oxford Textbook of Old Age Psychiatry by : Tom Dening
Download or read book Oxford Textbook of Old Age Psychiatry written by Tom Dening and published by Oxford University Press, USA. This book was released on 2020-11-05 with total page 961 pages. Available in PDF, EPUB and Kindle. Book excerpt: Part of the authoritative Oxford Textbooks in Psychiatry series, Oxford Textbook of Old Age Psychiatry, Third Edition has been thoroughly updated to reflect the developments in old age psychiatry since publication of the Second Edition in 2013, and remains an essential reference for anyone interested in the mental health care of older people.
Book Synopsis Gene Therapy of the Central Nervous System: From Bench to Bedside by : Michael G. Kaplitt
Download or read book Gene Therapy of the Central Nervous System: From Bench to Bedside written by Michael G. Kaplitt and published by Elsevier. This book was released on 2005-11-11 with total page 372 pages. Available in PDF, EPUB and Kindle. Book excerpt: Few areas of biomedical research provide greater opportunities for radically new therapies for devastating diseases that have evaded treatment so far than gene therapy. This is particularly true for the brain and nervous system, where gene transfer has become a key technology for basic research and has recently been translated to human therapy in several landmark clinical trials. Gene Therapy of the Central Nervous System: From Bench to Bedside represents the first definitive volume on this subject. Edited by two pioneers of neurological gene therapy, this volume contains contributions by leaders who helped create this field and are expanding the promise of gene therapy for the future of basic and clinical neuroscience. Drawing upon this extensive collective experience, this book provides clear and informative reviews on a variety of subjects of interest to anyone exploring or using gene therapy for neurobiological applications in research and clinical praxis.* Presents gene transfer technologies with particular emphases upon novel vehicles, immunological issues and the role of gene therapy in stem cells* Discusses preclinical areas that are likely to translate into clinical studies in the near future, including epilepsy, pain and amyotrophic lateral sclerosis* Includes "insider" information on technological and regulatory issues which can often limit effective translation of even the most promising idea into clinical use
Book Synopsis Rab GTPases by : Guangpu Li (Molecular biologist)
Download or read book Rab GTPases written by Guangpu Li (Molecular biologist) and published by . This book was released on 2021 with total page 310 pages. Available in PDF, EPUB and Kindle. Book excerpt: This second edition volume expands on the previous edition with a discussion of new research and discoveries in the Rab field. Chapters in this book cover topics such as new information on Rab regulation and localization; interaction; function; and diseases. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and comprehensive, Rab GTPases: Methods and Protocols, Second Edition is a valuable resource for scientists working in the fields of Rab and other small GTPases, and beyond.