Protein Degradation Aggregation Membrane Trafficking And Exosomes In Neuronal Health And Disease
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Protein Degradation Aggregation Membrane Trafficking And Exosomes In Neuronal Health And Disease
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Author : Beatriz Alvarez
language : en
Publisher: Frontiers Media SA
Release Date : 2022-08-02
Protein Degradation Aggregation Membrane Trafficking And Exosomes In Neuronal Health And Disease written by Beatriz Alvarez and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2022-08-02 with Science categories.
Mesenchymal Stem Cell Derived Exosomes
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Author : Yaoliang Tang
language : en
Publisher: Academic Press
Release Date : 2015-09-02
Mesenchymal Stem Cell Derived Exosomes written by Yaoliang Tang and has been published by Academic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2015-09-02 with Medical categories.
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
The Propagation Of Neurodegenerative Diseases By Inflammation And Exosomes
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Author : Valerie Sackmann
language : en
Publisher: Linköping University Electronic Press
Release Date : 2019-10-16
The Propagation Of Neurodegenerative Diseases By Inflammation And Exosomes written by Valerie Sackmann and has been published by Linköping University Electronic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2019-10-16 with categories.
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.
Leucine Rich Repeat Kinase 2 Lrrk2
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Author : Hardy J. Rideout
language : en
Publisher: Springer
Release Date : 2017-03-28
Leucine Rich Repeat Kinase 2 Lrrk2 written by Hardy J. Rideout and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017-03-28 with Medical categories.
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.
Dopamine Handbook
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Author : Leslie L. Iversen
language : en
Publisher: Oxford University Press, USA
Release Date : 2010
Dopamine Handbook written by Leslie L. Iversen and has been published by Oxford University Press, USA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2010 with Medical categories.
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. This publication captures current progress and excitement in this dynamic research field.--[Source inconnue].
Neuroanatomy And Pathology Of Sporadic Parkinson S Disease
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Author : Heiko Braak
language : en
Publisher: Springer
Release Date : 2008-12-03
Neuroanatomy And Pathology Of Sporadic Parkinson S Disease written by Heiko Braak and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2008-12-03 with Medical categories.
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.
Exosomes In Brain Health And Disease
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Author : Konstantin Glebov
language : en
Publisher: Frontiers Media SA
Release Date : 2022-06-06
Exosomes In Brain Health And Disease written by Konstantin Glebov and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2022-06-06 with Science categories.
Ubiquitin Proteasome System
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Author : Matthew Summers
language : en
Publisher: BoD – Books on Demand
Release Date : 2019-06-19
Ubiquitin Proteasome System written by Matthew Summers and has been published by BoD – Books on Demand this book supported file pdf, txt, epub, kindle and other format this book has been release on 2019-06-19 with Science categories.
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.
Neuronal Cell Death
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Author : Laura Lossi
language : en
Publisher: Humana
Release Date : 2016-08-23
Neuronal Cell Death written by Laura Lossi and has been published by Humana this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016-08-23 with Medical categories.
This volume represents a valuable and readily reproducible collection of established and emerging techniques for neuronal cell death research. Conveniently divided into four parts, sections cover a series of techniques for the molecular, structural, functional and genomic characterization of dying neurons, a number of protocols that are of primary interest in neuropathology and in experimental neuropathology, a series of gene engineering techniques to obtain and manipulate neuronal stem cells and progenitors, to prepare HSV-1 vectors for the gene therapy, and to CNS transplantation of bone marrow stem cells, and finally, some very interesting protocols for the study of cell death in non-mammalian models. Written in the 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 protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, Neuronal Cell Death: Methods and Protocols seeks to serve a large audience of scientists that are currently active in the field or are willing to enter such an exciting and still expanding area of neurobiology.
Extracellular Vesicles
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Author :
language : en
Publisher: Academic Press
Release Date : 2020-11-08
Extracellular Vesicles written by and has been published by Academic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020-11-08 with Science categories.
Extracellular Vesicles, Volume 645 in the Methods in Enzymology series, continues the legacy of this premier serial with quality chapters authored by leaders in the field. Chapters in this new release include Genetic labeling of extracellular vesicle exosomes for studying biogenesis and uptake in living mammalian cells, Fluorescent Labeling of Extracellular Vesicles, Isolation of extracellular vesicles from lymph, Transgenic rats for tracking body fluid/tissue-derived extracellular vesicles, Isolation of amniotic extracellular vesicles, Urinary extracellular vesicle isolation, Immunocapture-based ELISA to Characterize and Quantify Extracellular Vesicles in Both Cell Culture Supernatants and Body Fluids, and much more. Provides the authority and expertise of leading contributors from an international board of authors Presents the latest release in the Methods in Enzymology series