Protein Aggregation And Propagation In Neurodegenerative Diseases

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Protein Misfolding and Spreading Pathology in Neurodegenerative Diseases

Author : Diana Fernandes Lázaro,Tiago F. Outeiro,Arianna Bellucci,Patrik Brundin
Publisher : Frontiers Media SA
Page : 158 pages
File Size : 41,6 Mb
Release : 2020-02-20
Category : Electronic
ISBN : 9782889635078

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Protein Misfolding and Spreading Pathology in Neurodegenerative Diseases by Diana Fernandes Lázaro,Tiago F. Outeiro,Arianna Bellucci,Patrik Brundin Pdf

This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact.

The Propagation of Neurodegenerative Diseases by Inflammation and Exosomes

Author : Valerie Sackmann
Publisher : Linköping University Electronic Press
Page : 60 pages
File Size : 49,9 Mb
Release : 2019-10-16
Category : Electronic
ISBN : 9789175190129

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The Propagation of Neurodegenerative Diseases by Inflammation and Exosomes by Valerie Sackmann Pdf

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.

Proteopathic Seeds and Neurodegenerative Diseases

Author : Mathias Jucker,Yves Christen
Publisher : Springer Science & Business Media
Page : 163 pages
File Size : 50,7 Mb
Release : 2013-03-27
Category : Medical
ISBN : 9783642354915

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Proteopathic Seeds and Neurodegenerative Diseases by Mathias Jucker,Yves Christen Pdf

The misfolding and aggregation of specific proteins is an early and obligatory event in many of the age-related neurodegenerative diseases of humans. The initial cause of this pathogenic cascade and the means whereby disease spreads through the nervous system, remain uncertain. A recent surge of research, first instigated by pathologic similarities between prion disease and Alzheimer’s disease, increasingly implicates the conversion of disease-specific proteins into an aggregate-prone b-sheet-rich state as the prime mover of the neurodegenerative process. This prion-like corruptive protein templating or seeding now characterizes such clinically and etiologically diverse neurological disorders as Alzheimer ́s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and frontotemporal lobar degeneration. Understanding the misfolding, aggregation, trafficking and pathogenicity of the affected proteins could therefore reveal universal pathomechanistic principles for some of the most devastating and intractable human brain disorders. It is time to accept that the prion concept is no longer confined to prionoses but is a promising concept for the understanding and treatment of a remarkable variety of diseases that afflict primarily our aging society. ​

Quality Control of Cellular Protein in Neurodegenerative Disorders

Author : Uddin, Md. Sahab,Ashraf, Ghulam Md.
Publisher : IGI Global
Page : 515 pages
File Size : 55,8 Mb
Release : 2020-02-14
Category : Medical
ISBN : 9781799813187

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Quality Control of Cellular Protein in Neurodegenerative Disorders by Uddin, Md. Sahab,Ashraf, Ghulam Md. Pdf

Protein misfolding and aggregation are hallmarks of several neurodegenerative proteinopathies. Though multiple factors like aging, oxidative stress, mitochondrial dysfunction, proteotoxic insults, genetic inconsistency, etc. are responsible for the dysfunction of the neuronal protein quality control system, targeting protein quality control has become an auspicious approach to halt the propagation of neurodegeneration. Quality Control of Cellular Protein in Neurodegenerative Disorders provides diverse aspects exploring the role of the protein quality control in neurodegenerative disorders and potential therapeutic strategies to combat the development and propagation of neurodegeneration. Featuring coverage on a broad range of topics such as molecular chaperones, protein misfolding, and stress signaling, this book is ideally designed for neurobiologists, neuropsychologists, neurophysiologists, medical professionals, neuropathologists, researchers, academicians, students, and practitioners engaged in studies of the protein quality control system in neuronal cells.

Fatal Attractions: Protein Aggregates in Neurodegenerative Disorders

Author : V.M.-Y. Lee,J.Q. Trojanowski,L. Buee,Y. Christen
Publisher : Springer Science & Business Media
Page : 164 pages
File Size : 44,7 Mb
Release : 2013-03-09
Category : Medical
ISBN : 9783662040560

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Fatal Attractions: Protein Aggregates in Neurodegenerative Disorders by V.M.-Y. Lee,J.Q. Trojanowski,L. Buee,Y. Christen Pdf

In this volume are contributions based on a meeting arranged by the WHO and the Fondation IPSEN. The scientists focus on neurodegenerative disorders like Alzheimer's Disease, Chromosome 17-Linked Dementia, Parkinson's Disease and disorders with tauopathies.

Neurodegenerative Diseases

Author : Uday Kishore
Publisher : BoD – Books on Demand
Page : 642 pages
File Size : 49,9 Mb
Release : 2013-05-15
Category : Medical
ISBN : 9789535110880

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Neurodegenerative Diseases by Uday Kishore Pdf

This book highlights the pathophysiological complexities of the mechanisms and factors that are likely to be involved in a range of neuroinflammatory and neurodegenerative diseases including Alzheimer's disease, other Dementia, Parkinson Diseases and Multiple Sclerosis. The spectrum of diverse factors involved in neurodegeneration, such as protein aggregation, oxidative stress, caspases and secretase, regulators, cholesterol, zinc, microglia, astrocytes, oligodendrocytes, etc, have been discussed in the context of disease progression. In addition, novel approaches to therapeutic interventions have also been presented. It is hoped that students, scientists and clinicians shall find this very informative book immensely useful and thought-provoking.

Protein Aggregation

Author : Douglas A. Stein
Publisher : Nova Biomedical Books
Page : 0 pages
File Size : 41,8 Mb
Release : 2011
Category : Cell aggregation
ISBN : 1617618152

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Protein Aggregation by Douglas A. Stein Pdf

Protein aggregation is the aggregation of mis-folded proteins, and is thought to be responsible for many degenerative diseases, such as Alzheimer's. This book presents current research from across the globe in the study of protein aggregation, including the processes of protein aggregation induced by freezing and lyophilization; functional amyloids; thermally induced aggregation of a model system protein - insulin; the aggregation of albumin; synucleins implicated in neurodegenerative diseases and some forms of cancer; yeast protein aggregates; and the folding and aggregation features of proteins.

Network Spread Models of Neurodegenerative Diseases

Author : Ashish Raj,Yasser Iturria Medina
Publisher : Frontiers Media SA
Page : 116 pages
File Size : 53,8 Mb
Release : 2019-04-18
Category : Electronic
ISBN : 9782889457687

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Network Spread Models of Neurodegenerative Diseases by Ashish Raj,Yasser Iturria Medina Pdf

It is a real pleasure to introduce the excellent papers contributed by leading experts to our Research Topic proposing various network models of dementia spread. The focus is strongly on disease-specific mathematical modeling rather than general graph theory. The emerging field of network neuroscience visualizes the brain as a graph consisting of nodes representing regions and edges as connections between them. This complex network supports efficient communication along neural projections, but also, unfortunately, the transmission and progression of Alzheimer’s and other neurodegenerative disorders. If we could know the brain’s network organization, could we then predict how degenerative processes might develop on this network? As these papers demonstrate, the answer is, increasingly, yes.

Protein Misfolding, Aggregation and Conformational Diseases

Author : Vladimir N. Uversky,Anthony Fink
Publisher : Springer Science & Business Media
Page : 450 pages
File Size : 45,5 Mb
Release : 2007-11-24
Category : Science
ISBN : 9780387259192

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Protein Misfolding, Aggregation and Conformational Diseases by Vladimir N. Uversky,Anthony Fink Pdf

Research indicates that most neurodegenerative diseases, systemic amyloidoses and many others, arise from the misfolding and aggregation of an underlying protein. This is the first book to discuss significant achievements in protein structure-function relationships in biochemistry, molecular biology and molecular medicine. The authors summarize recent progress in the understanding of the relationships between protein misfolding, aggregation and development of protein deposition disorders.

The Molecular and Cellular Basis of Neurodegenerative Diseases

Author : Michael S. Wolfe
Publisher : Academic Press
Page : 560 pages
File Size : 41,7 Mb
Release : 2018-03-29
Category : Medical
ISBN : 9780128113059

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The Molecular and Cellular Basis of Neurodegenerative Diseases by Michael S. Wolfe Pdf

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

Protein Quality Control in Neurodegenerative Diseases

Author : Richard I. Morimoto,Yves Christen
Publisher : Springer Science & Business Media
Page : 145 pages
File Size : 53,7 Mb
Release : 2012-12-13
Category : Medical
ISBN : 9783642279287

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Protein Quality Control in Neurodegenerative Diseases by Richard I. Morimoto,Yves Christen Pdf

The health of the proteome depends upon protein quality control to regulate the proper synthesis, folding, translocation, and clearance of proteins. The cell is challenged constantly by environmental and physiological stress, aging, and the chronic expressions of disease associated misfolded proteins. Substantial evidence supports the hypothesis that the expression of damaged proteins initiates a cascade of molecular events that leads to Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and other diseases of protein conformation.

Spectrums of Amyotrophic Lateral Sclerosis

Author : Christopher A. Shaw,Jessia R. Morrice
Publisher : John Wiley & Sons
Page : 240 pages
File Size : 46,6 Mb
Release : 2021-04-20
Category : Medical
ISBN : 9781119745501

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Spectrums of Amyotrophic Lateral Sclerosis by Christopher A. Shaw,Jessia R. Morrice Pdf

SPECTRUMS OF AMYOTROPHIC LATERAL SCLEROSIS Discover state-of-the-art research findings on ALS from leading authors and editors in the field In Spectrums of Amyotrophic Lateral Sclerosis: Heterogeneity, Pathogenesis & Therapeutic Directions, distinguished researchers and editors Dr. Christopher A. Shaw and Jessica R. Morrice deliver a practical and powerful perspective on Amyotrophic Lateral Sclerosis (ALS) as a heterogeneous spectrum of disorders. This increasingly accepted point-of-view allows researchers and medical professionals to develop better targeted interventions and more precise therapies. In the book, readers will find chapters on a wide variety of critical issues facing ALS researchers and healthcare practitioners treating ALS sufferers, including animal models of ALS, neuronal support cells known to have a pivotal role in ALS, and current challenges in ALS clinical trials, among others. The authors describe pathologic features common to all cases of ALS and why animal models, though crucial, should be interpreted with caution. Finally, multiple genetic and environmental etiologies of the disease are discussed. Readers will also benefit from the inclusion of: A thorough introduction to ALS as a spectrum disease and the implications for models, therapeutic development and clinical trial design Explorations of the genetic basis of ALS, prospective sALS etiologies, and the involvement of microbiome in ALS Discussions of ALS-PDC and environmental risk factors, protein aggregation in ALS, defects in RNA metabolism in ALS, and the non-cell autonomous nature of ALS and the involvement of glial cells Examinations of animal models of ALS and perspectives on previously failed ALS therapeutics and current therapeutic strategies Perfect for clinical neurologists, healthcare providers and caretakers, clinicians, and researchers studying motor neuron disease, Spectrums of Amyotrophic Lateral Sclerosis: Heterogeneity, Pathogenesis & Therapeutic Directions is also an indispensable resource for the neurodegenerative research community, neurology residents, and graduate-level neuroscience students.

Disease-Modifying Targets in Neurodegenerative Disorders

Author : Veerle Baekelandt,Evy Lobbestael
Publisher : Academic Press
Page : 324 pages
File Size : 53,7 Mb
Release : 2017-03-31
Category : Medical
ISBN : 9780128052662

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Disease-Modifying Targets in Neurodegenerative Disorders by Veerle Baekelandt,Evy Lobbestael Pdf

Disease-Modifying Targets in Neurodegenerative Disorders: Paving the Way for Disease-Modifying Therapies examines specific neurodegenerative disorders in comprehensive chapters written by experts in the respective fields. Each chapter contains a summary of the disease management field, subsequently elaborating on the molecular mechanisms and promising new targets for disease-modifying therapies. This overview is ideal for neuroscientists, biomedical researchers, medical doctors, and caregivers, not only providing readers with a summary of the way patients are treated today, but also offering a glance at the future of neurodegenerative disorder treatment. Provides a comprehensive overview of how key proteins in neurodegenerative disorders can be used as targets to modify disease progress Summarizes how patients are treated today, providing a glance at future disease management Includes intelligible and informative information that is perfect for non-specialists, medical practitioners, and scientists Written and peer reviewed by outstanding scientists in their respective fields

Protein Degradation, Aggregation, Membrane Trafficking and Exosomes in Neuronal Health and Disease

Author : Beatriz Alvarez,Miguel Diaz-Hernandez,Douglas Campbell,Irena Vlatkovic
Publisher : Frontiers Media SA
Page : 155 pages
File Size : 46,7 Mb
Release : 2022-08-02
Category : Science
ISBN : 9782889766758

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Protein Degradation, Aggregation, Membrane Trafficking and Exosomes in Neuronal Health and Disease by Beatriz Alvarez,Miguel Diaz-Hernandez,Douglas Campbell,Irena Vlatkovic Pdf