Common Pathways Linking Neurodegenerative Diseases The Role Of Inflammation

Author : Grzegorz Kreiner
Publisher : Frontiers Media SA
ISBN 13 : 2889715639
Total Pages : 280 pages
Book Rating : 4.33/5 ( download)

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Download or read book Common Pathways Linking Neurodegenerative Diseases – The Role of Inflammation written by Grzegorz Kreiner and published by Frontiers Media SA. This book was released on 2021-11-01 with total page 280 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Author : Valerie Sackmann
Publisher : Linköping University Electronic Press
ISBN 13 : 9175190125
Total Pages : 60 pages
Book Rating : 4.29/5 ( download)

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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.

Author : Maya Koronyo-Hamaoui
Publisher : Frontiers Media SA
ISBN 13 : 2889765628
Total Pages : 461 pages
Book Rating : 4.21/5 ( download)

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Download or read book Role of Inflammation in Neurodegenerative Diseases written by Maya Koronyo-Hamaoui and published by Frontiers Media SA. This book was released on 2022-07-13 with total page 461 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Author :
Publisher : Elsevier Health Sciences
ISBN 13 : 9780323044042
Total Pages : 1578 pages
Book Rating : 4.42/5 ( download)

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Download or read book Clinical immunology written by and published by Elsevier Health Sciences. This book was released on 2008 with total page 1578 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Author :
Publisher :
ISBN 13 :
Total Pages : 538 pages
Book Rating : 4.2E/5 ( download)

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Download or read book Transactions of the Royal Society of South Australia, Incorporated written by and published by . This book was released on 1978 with total page 538 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Author : Rosa Barrio
Publisher : Springer Nature
ISBN 13 : 3030382664
Total Pages : 350 pages
Book Rating : 4.67/5 ( download)

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Download or read book Proteostasis and Disease written by Rosa Barrio and published by Springer Nature. This book was released on 2020-04-09 with total page 350 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book, written by members of the European network PROTEOSTASIS, provides an up-to-date review of the research regarding protein homeostasis in health and disease. With new discoveries contributing to the increasing complexity of this topic, the book offers a detailed overview of the pathways regulating protein homeostasis, including autophagy and the ubiquitin protein family. Following a basic introduction, it explains how defects in protein homeostasis contribute to numerous pathologies, including cancer, neurodegeneration, inflammation and a number of rare diseases. In addition, it discusses, the role of protein homeostasis in cellular development and physiology. Highlighting the latest research in the field of protein homeostasis and its implications for various clinically relevant diseases, the book appeals to researchers and clinicians, while also offering a reference guide for scholars who are new to the field.

Author : Jesus Avila
Publisher : Frontiers E-books
ISBN 13 : 288919261X
Total Pages : 114 pages
Book Rating : 4.18/5 ( download)

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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”.

Author : Michael S. Wolfe
Publisher : Academic Press
ISBN 13 : 0128113057
Total Pages : 560 pages
Book Rating : 4.59/5 ( download)

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Download or read book The Molecular and Cellular Basis of Neurodegenerative Diseases written by Michael S. Wolfe and published by Academic Press. This book was released on 2018-03-29 with total page 560 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Molecular and Cellular Basis of Neurodegenerative Diseases: Underlying Mechanisms presents the pathology, genetics, biochemistry and cell biology of the major human neurodegenerative diseases, including Alzheimer’s, Parkinson’s, frontotemporal dementia, ALS, Huntington’s, and prion diseases. Edited and authored by internationally recognized leaders in the field, the book's chapters explore their pathogenic commonalities and differences, also including discussions of animal models and prospects for therapeutics. Diseases are presented first, with common mechanisms later. Individual chapters discuss each major neurodegenerative disease, integrating this information to offer multiple molecular and cellular mechanisms that diseases may have in common. This book provides readers with a timely update on this rapidly advancing area of investigation, presenting an invaluable resource for researchers in the field. Covers the spectrum of neurodegenerative diseases and their complex genetic, pathological, biochemical and cellular features Focuses on leading hypotheses regarding the biochemical and cellular dysfunctions that cause neurodegeneration Details features, advantages and limitations of animal models, as well as prospects for therapeutic development Authored by internationally recognized leaders in the field Includes illustrations that help clarify and consolidate complex concepts

Author : G. Ali Qureshi
Publisher : Elsevier
ISBN 13 : 0080489494
Total Pages : 795 pages
Book Rating : 4.90/5 ( download)

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Download or read book Oxidative Stress and Neurodegenerative Disorders written by G. Ali Qureshi and published by Elsevier. This book was released on 2007-03-22 with total page 795 pages. Available in PDF, EPUB and Kindle. Book excerpt: Oxidative stress is the result of an imbalance in pro-oxidant/antioxidant homeostasis that leads to the generation of toxic reactive oxygen species. Brain cells are continuously exposed to reactive oxygen species generated by oxidative metabolism, and in certain pathological conditions defense mechanisms against oxygen radicals may be weakened and/or overwhelmed. DNA is a potential target for oxidative damage, and genomic damage can contribute to neuropathogenesis. It is important therefore to identify tools for the quantitative analysis of DNA damage in models on neurological disorders. This book presents detailed information on various neurodegenerative disorders and their connection with oxidative stress. This information will provide clinicians with directions to treat these disorders with appropriate therapy and is also of vital importance for the drug industries for the design of new drugs for treatment of degenerative disorders. * Contains the latest information on the subject of neurodegenerative disorders* Reflects on various factors involved in degeneration and gives suggestions for how to tackle these problems

Author : Marie-Francoise Chesselet
Publisher : Springer Science & Business Media
ISBN 13 : 1592590063
Total Pages : 416 pages
Book Rating : 4.63/5 ( download)

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Download or read book Molecular Mechanisms of Neurodegenerative Diseases written by Marie-Francoise Chesselet and published by Springer Science & Business Media. This book was released on 2000-10-19 with total page 416 pages. Available in PDF, EPUB and Kindle. Book excerpt: With the unprecedented identification of new mutation mechanisms in neurodegenerative diseases and the emergence of common mechanisms among diseases that were once considered unrelated, neurobiologists are poised for the development of new therapies based on high throughput screenings and a better understanding of the molecular and cellular mechanisms leading to neurodegeneration. In Molecular Mechanisms of Neurodegenerative Diseases, Marie-Francoise Chesselet, MD, PhD, and a panel of leading researchers and neurologists from industry and academia critically review the most recent advances from different yet complementary points of view. Focusing on Alzheimer's, Parkinson's, and CAG triplet repeat diseases, the authors show how studies of cellular and genetically engineered animal models have enhanced our understanding of the molecular mechanisms of neurodegenerative diseases and may lead to the development of new therapeutics. Topics include the role of Ab toxicity, glial cells, and inflammation in Alzheimer's disease; the formation of abnormal protein fragments across several diseases, the impact of dopamine and mitochondrial dysfunction on neurodegeneration; and the potential of genetics to identify the molecular mechanisms of neurodegenerative diseases. Authoritative and insightful, Molecular Mechanisms of Neurodegenerative Diseases synthesizes the novel ideas and concepts now emerging to create a fresh understanding of neurodegenerative disorders, one that promises to lead to powerful new therapies that prevent, delay the onset, slow the progression, or even cure these cruel diseases.