The Propagation Of Neurodegenerative Diseases By Inflammation And Exosomes
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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.
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 Science 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
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.
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
Tau Oligomers
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Author : Jesus Avila
language : en
Publisher: Frontiers E-books
Release Date : 2014-08-18
Tau Oligomers written by Jesus Avila and has been published by Frontiers E-books this book supported file pdf, txt, epub, kindle and other format this book has been release on 2014-08-18 with Medicine (General) categories.
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”.
Role Of Exosomes In Biological Communication Systems
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Author : Faisal A. Alzahrani
language : en
Publisher: Springer Nature
Release Date : 2020-11-20
Role Of Exosomes In Biological Communication Systems written by Faisal A. Alzahrani and has been published by Springer Nature this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020-11-20 with Medical categories.
This book reviews the role of exosomes and extracellular vesicles in both normal and pathological conditions. It first explains isolation methods for exosomes, and analyzes their fine structure and biological functions. Further, it highlights exosomes’ role as the key regulator in embryonic-maternal communication, and in the pathogenesis of various diseases, including cancer and urogenital, infectious, and neurodegenerative diseases. Moreover, it reviews the latest advances in using stem-cell-derived exosomes as a cell-free strategy in regenerative medicine, as well as the potential of exosomal microRNA as a promising non-invasive biomarker and targetable factor in cancer diagnosis and treatment. Lastly, it explores the use of natural and synthetic exosomes as nano-vehicles for efficient drug delivery.
The Physiology Of Inflammation The Final Common Pathway To Disease
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Author : Alexandrina Ferreira Mendes
language : en
Publisher: Frontiers Media SA
Release Date : 2019-02-20
The Physiology Of Inflammation The Final Common Pathway To Disease written by Alexandrina Ferreira Mendes 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 2019-02-20 with categories.
Chronic diseases are increasingly recognized as involving low grade inflammation, that is, a self-perpetuating tissue response to stress caused by exogenous or endogenous triggers, that progressively evokes danger-associated molecular pattern release, ultimately driving tissue damage and loss of function. This response is frequently unapparent clinically, thus the designation "low grade". This eBook comprises nineteen reviews and original articles that provide the most updated knowledge on the causes and roles of this inflammatory response in a variety of diseases and conditions. The editorial that precedes these articles not only summarizes each one, but provides a broader interpretation of the role of inflammation in health and a variety of disease conditions, the underlying mechanisms and the targets more promising for therapy. Finally, it also highlights the most relevant and emerging research topics that are already shaping future directions for the development of more fine-tuned and innovative therapies.
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.
Extracellular Vesicles And Their Importance In Human Health
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Author : Ana Gil De Bona
language : en
Publisher: BoD – Books on Demand
Release Date : 2020-03-04
Extracellular Vesicles And Their Importance In Human Health written by Ana Gil De Bona 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 2020-03-04 with Science categories.
Extracellular vesicle is a wide term that involves many different types of vesicles. Almost all the cell types studied secrete vesicles to the extracellular environment related to cell - cell communication. Extracellular vesicles have been found in different biological fluids, such as blood, milk, saliva, tears, urine, and cerebrospinal fluid. These vesicles transport different molecules, including mRNA, proteins, and lipids, some of them cell type specific that make them ideal biomarkers in both health and disease conditions. However, their contribution to different conditions is not well understood. The aim of this book is to provide an overview of the extracellular vesicles in the human body, how they are internalized, and their participation in several diseases.
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.