Exosomes In Brain Health And Disease
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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.
Exosomes Based Drug Delivery Strategies For Brain Disorders
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Author : Neeraj Mishra
language : en
Publisher: Springer Nature
Release Date :
Exosomes Based Drug Delivery Strategies For Brain Disorders written by Neeraj Mishra and has been published by Springer Nature this book supported file pdf, txt, epub, kindle and other format this book has been release on with categories.
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.
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
Applications Of Stem Cells And Derived Exosomes In Neurodegenerative Disorders
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Author : Sadaf Jahan
language : en
Publisher: Springer Nature
Release Date :
Applications Of Stem Cells And Derived Exosomes In Neurodegenerative Disorders written by Sadaf Jahan and has been published by Springer Nature this book supported file pdf, txt, epub, kindle and other format this book has been release on with categories.
Brain Extracellular Matrix In Health And Disease
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Author : Alexander Dityatev
language : en
Publisher:
Release Date : 2014
Brain Extracellular Matrix In Health And Disease written by Alexander Dityatev and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2014 with Brain categories.
Exosomes
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Author : Larry Edelstein
language : en
Publisher: Academic Press
Release Date : 2019-10-16
Exosomes written by Larry Edelstein and has been published by Academic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2019-10-16 with Science categories.
Exosomes: A Clinical Compendium is a comprehensive and authoritative account of exosomes in the context of biomarkers, diagnostics, and therapeutics across a wide spectrum of medical disciplines, as well as their role in cell-cell communication. It is intended to serve as a reference source for clinicians, physicians, and research scientists who wish to gain insight into the most recent advances in this rapidly growing field. The exosome revolution may well be the greatest advance in physiology and medicine since antibiotics. The discovery of their epigenetic role in intercellular signaling in virtually all tissues is a major breakthrough in our understanding of how cells function. Provides readers with a broad and timely overview of exosomes in health and disease, closing with a thought-provoking chapter on transgenerational inheritance, Darwin and Lamarck. Summarizes the most recent laboratory and clinical findings on exosomes across numerous medical disciplines, thereby offering readers a broad-ranging and solid foundation for prospective investigative efforts Twenty-one chapters authored by a global team of peer-acknowledged experts, each representing a key medical disciplineProvides readers with a broad and timely overview of exosomes in health and disease, closing
Cerebral Ischemia
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Author : Ryszard M. Pluta
language : en
Publisher:
Release Date : 2021
Cerebral Ischemia written by Ryszard M. Pluta and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2021 with categories.
Cerebral ischemia is one of the most common causes of dementia, which develops in more than half of patients after an ischemic episode. The main mechanism is thought to be pathological changes in the hippocampus, especially in the CA1 area, underlying episodic memory impairment, which is the earliest and most important clinical symptom of post-ischemic dementia. The 13 chapters of this book present a new picture of ischemic brain disease, synthesizing the latest data on disease mechanisms, care for patients with this disease, and potential therapeutic targets. The authors present the characteristics of cerebral ischemia from pregnancy and childhood through adolescence to adulthood. The first two chapters provide a snapshot of the anatomy of the cerebral cortex and the hippocampus, the most affected brain structures after cerebral ischemia. This is followed by nine chapters that present a comprehensive view of the pathological mechanisms of cerebral ischemia, and how a deep understanding of these pathomechanisms hold the key for the discovery and development of novel therapies to help patients affected by cerebral ischemia. Chapter 12 shares real-life experience and challenges of rehabilitating patients into the community after cerebral ischemia, and chapter 13 analyzes the social risk variations, including gender inequality, in the reintegration of post-ischemic stroke patients. Although primarily aimed at scientists and clinicians, the contents of the book will be of interest to all those who are interested in cerebral ischemia, including patients and their caregivers.
Exosomes In Cardiovascular Diseases
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Author : Junjie Xiao
language : en
Publisher: Springer
Release Date : 2017-09-19
Exosomes In Cardiovascular Diseases written by Junjie Xiao and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017-09-19 with Science categories.
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.