Protein Misfolding In Neurodegenerative Diseases

Author: Robert D. E. Sewell
Editor: CRC Press
ISBN: 9781420007145
File Size: 12,17 MB
Format: PDF
Read: 6954
Download

Research focused on protein folding, misfolding, and aggregation is leading to major advances across biochemistry and medicine. The elucidation of a folding code is proving to be of extreme importance in the postgenomic era, where a number of orphan genes have been identified for which no clear function has yet been established. This research is starting to shed light on the molecular and biochemical basis of a number of neurodegenerative diseases of dramatic impact. Protein Misfolding in Neurodegenerative Diseases: Mechanisms and Therapeutic Strategies addresses key issues concerning protein misfolding and aggregation in neurodegenerative diseases. Building on recent developments, including the recognition of protein misfolding as both a marker and a causal agent, the text presents the work of those who are actively pursuing more effective treatments, as well as preventative measures, and a possible cure. These include the use of molecular chaperones to control misfolding and novel pharmaceuticals, as well as the potential role of various inhibitors and NSAIDS. A Comprehensive Multifaceted Examination of the Complex Causal Agents Implicated in Protein Misfolding Divided into five sections, this groundbreaking text provides up-to-date accounts for Alzheimer’s, Parkinson’s, Huntington’s, Amyotrophic Lateral Sclerosis and Transmissible Spongiform Encephalitis. It also explores the highly likelihood that multiple factors, including oxidative stress, play a role in these complex diseases.

Protein Misfolding And Disease

Author: Peter Bross
Editor: Springer Science & Business Media
ISBN: 1592593941
File Size: 30,83 MB
Format: PDF, Kindle
Read: 7207
Download

This volume presents a comprehensive review of the latest thinking about the molecular processes underlying conformational diseases, combined with a remarkable set of biochemical, genomic cellular, and chemical laboratory techniques for studying their genesis and pathologies. The authors apply their carefully refined methods to a variety of metabolic and neurodegenerative disorders, as well as to the aging process. The techniques presented are broadly applicable in many diverse disease contexts and may be used in both diagnosis and research on new treatment strategies. Use proven techniques for the study of diseases attributable to protein misfolding Understand conformational disease mechanisms in metabolic and neurodegenerative disorders Develop new treatment strategies Uncover new ideas and new angles of investigation.

Protein Misfolding And Spreading Pathology In Neurodegenerative Diseases

Author: Diana Fernandes Lázaro
Editor: Frontiers Media SA
ISBN: 2889635074
File Size: 39,80 MB
Format: PDF, Docs
Read: 6518
Download


Molecular Targets In Protein Misfolding And Neurodegenerative Disease

Author: Pierfausto Seneci
Editor: Academic Press
ISBN: 0128004991
File Size: 60,88 MB
Format: PDF, ePub, Docs
Read: 5691
Download

Aimed at "drug discoverers" – i.e. any scientist who is interested in neurodegenerative diseases in general, and in finding disease-modifying treatments in particular – the first edition of Molecular Targets in Protein Misfolding and Neurodegenerative Disease will contain both a detailed, discipline-specific coverage (paragraphs on medicinal chemistry, on clinical and preclinical characterization of compounds in development, on target identification and validation, on genetic factors influencing a pathology, etc.) and a drug discovery-oriented, overall evaluation of each target (validation, druggability, existing leads, etc.). Together these will satisfy the needs of various audiences, including in vitro biologists, pharmacologists, medicinal chemists, etc. Written to provide a comprehensive coverage of disease-modifying mechanisms and compounds against neurodegenerative diseases Provides a “drug discovery application oriented perspective, evaluating targets and candidates for their overall therapeutic potential Provides discipline-specific chapters (medicinal chemistry, target validation, preclinical and clinical development Provides an overview on a number of molecular mechanisms (e.g. phosphorylation, chaperon refolding, ubiquitination, autophagy, microtubule transportation, protease cleavage, etc.) with relevance for any disease area Contains a more thorough description of the therapeutic relevance of ~10 specific molecular targets

Fundamentals Of Neurodegeneration And Protein Misfolding Disorders

Author: Martin Beckerman
Editor: Springer
ISBN: 3319221175
File Size: 54,71 MB
Format: PDF, ePub
Read: 2971
Download

This unique text introduces students and researchers to the world of misfolded proteins, toxic oligomers, and amyloid assemblages, and the diseases of the brain that result. During the past few years the connections between failures in protein quality control and neurological disorders have been reinforced and strengthened by discoveries on multiple fronts. These findings provide novel insights on how amyloidogenic oligomers and fibrils form, interconvert from one state to another, and propagate from cell to cell and region to region. Starting with protein folding and protein quality control basics, the reader will learn how misfolded proteins can cause diseases ranging from prion diseases to Alzheimer’s disease and Parkinson’s disease to Huntington’s disease, amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Authoritative but written in a clear and engaging style, Fundamentals of Neurodegeneration and Protein Misfolding Disorders addresses one of today’s forefront areas of science and medicine. The text emphasizes the new groundbreaking biophysical and biochemical methods that enable molecular-level explorations and the conceptual breakthroughs that result. It contains separate chapters on each of the major disease classes. Special emphasis is placed on those factors and themes that are common to the diseases, especially failures in synaptic transmission, mitochondrial control, and axonal transport; breakdowns in RNA processing; the potential role of environmental factors; and the confounding effects of neuroinflammation. The book is ideal for use in teaching at the advanced undergraduate and graduate levels, and serves as a comprehensive reference for a broad audience of students and researchers in neuroscience, molecular biology, biological physics and biomedical engineering.

Protein Misfolding Aggregation And Conformational Diseases

Author: Vladimir N. Uversky
Editor: Springer Science & Business Media
ISBN: 0387259198
File Size: 36,30 MB
Format: PDF
Read: 6451
Download

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.

Protein Misfolding Diseases

Author: Marina Ramirez-Alvarado
Editor: John Wiley & Sons
ISBN: 9781118031810
File Size: 29,68 MB
Format: PDF, ePub, Mobi
Read: 167
Download

An increasingly aging population will add to the number of individuals suffering from amyloid. Protein Misfolding Diseases provides a systematic overview of the current and emerging therapies for these types of protein misfolding diseases, including Alzheimer's, Parkinson's, and Mad Cow. The book emphasizes therapeutics in an amyloid disease context to help students, faculty, scientific researchers, and doctors working with protein misfolding diseases bridge the gap between basic science and pharmaceutical applications to protein misfolding disease.

Genotype Proteotype Phenotype Relationships In Neurodegenerative Diseases

Author: J. Cummings
Editor: Springer Science & Business Media
ISBN: 3540265228
File Size: 46,56 MB
Format: PDF, ePub, Docs
Read: 2097
Download

Recent advances in understanding the role of protein dysmetabolism in neurodegeneration was the theme of the Fondation IPSEN meeting addressing Genotype-Proteotype-Phenotype relationships. Experts from international laboratories contributed to the current volume to produce a comprehensive overview of the role of protein misfolding in neurodegeneration. Links between genotype and protein characteristics and between proteotype and clinical phenomenology were discussed across diseases categories. Progress in understanding the role of abnormalities of protein metabolism may lead to the identification of biological markers relevant to disease monitoring and to the development of new therapeutic agents capable of modifying and ameliorating basic neurodegenerative mechanisms.

Protein Folding And Misfolding Neurodegenerative Diseases

Author: Judit Ovádi
Editor: Springer Science & Business Media
ISBN: 1402094345
File Size: 80,53 MB
Format: PDF, Mobi
Read: 3889
Download

Offering all the latest in the study of neurodegenerative diseases, this book reviews the molecular events initiated by unfolded or misfolded proteins leading to conformational human diseases, especially those found in Parkinson’s and Alzheimer’s diseases.

Template Directed Protein Misfolding In Neurodegenerative Disease

Author: William Clay Guest
Editor:
ISBN:
File Size: 55,82 MB
Format: PDF, Kindle
Read: 6868
Download


Role Of Misfolded Proteins In The Pathogenesis Of Neurodegenerative Disorders And Challenges Impacting The Development Of Novel Therapies An Overview

Author: Dr.Hakim Saboowala
Editor: Dr.Hakim Saboowala
ISBN:
File Size: 39,54 MB
Format: PDF, Docs
Read: 8323
Download

Role of Misfolded Proteins in the Pathogenesis of Neurodegenerative Disorders and Challenges impacting the development of Novel Therapies. An Overview. A hallmark of neurodegenerative proteinopathies is the formation of misfolded protein aggregates that cause cellular toxicity and contribute to cellular proteostatic collapse. Therapeutic targeting of protein misfolding has generated unique challenges for drug discovery and development for several reasons, including: 1)The dynamic nature of the protein species involved, 2)Uncertainty about which forms of a given disease protein such as Monomers, Oligomers, or Insoluble aggregates, are primarily responsible for cellular toxicity, 3)Our still limited understanding about which components of the cellular proteo-static machinery these disease proteins interact with and 4) Lack of well-validated biomarkers for clinical trials. Therapeutic options are currently being explored that target different steps in the production and processing of proteins implicated in neurodegenerative disease, including synthesis, chaperone-assisted folding and trafficking, and degradation via the proteasome and autophagy pathways. Other therapies, like mTOR inhibitors and activators of the heat shock response, can rebalance the entire proteostatic network. Hence an attempt has been made in this E-Booklet to discuss major challenges that impact the development of novel therapies, including incomplete knowledge of druggable disease targets and their mechanism of action as well as a lack of biomarkers to monitor disease progression and therapeutic response. …Dr. H. K. Saboowala. M.B.(Bom) .M.R.S.H.(London)

Protein Misfolding Disorders

Author: Claudio Hetz
Editor: Bentham Science Publishers
ISBN: 1608050130
File Size: 66,39 MB
Format: PDF, ePub, Mobi
Read: 4689
Download

Neurodegenerative disorders such as Amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD), Parkinson’s disease (PD), Prion-related disorders (PrD) and Huntington’s disease (HD) share a common neuropathology, primarily featuring the presence of abnormal protein inclusions containing specific misfolded proteins. These groups of diseases are now classified as Protein Misfolding Disorders. This book gives a comprehensive overview of the possible mechanisms involved in Protein Misfolding Disorders and possible therapeutic strategies to treat these diseases. The Ebook provides the most recent evidence addressing the role of cellular stress responses to neurological diseases, along with therapeutic strategies to alleviate ER stress in a disease context. -- Publisher.

What Causes Protein Misfolding And Toxicity In Neurodegenerative Disease

Author: Ashley A. Zurawel
Editor:
ISBN:
File Size: 19,70 MB
Format: PDF, ePub, Docs
Read: 676
Download

Central to many neurodegenerative diseases is protein aggregation leading to pathogenesis. Prion disease is characterized by a central misfolding event of PrP[superscript C] into the disease causing conformer, PrP[superscript Sc], yet the mechanism central to this event is not well understood. In Huntington’s disease, huntingtin with an expanded polyQ region aggregates and results in altered protein-protein interactions, yet how exactly this results in pathogenesis remains unanswered. I demonstrate that the interaction between PrP and a conversion cofactor 1- palmitoyl-2-oleoyl-sn-glycero-3-phophoglycerol (POPG) used to make infectious, recombinant PrP[superscript Sc] in vitro leads to the unmasking of the PrP polybasic domain, critical to PrP[superscript C]-PrP[superscriptSc] replicative interface. I also demonstrate that this interaction leads to structural changes in PrP such as aggregation and reorganization of the N-terminal region. Using two eukaryotic model organisms, I demonstrate the influence of polyQ containing proteins on huntingtin toxicity and aggregation. I show that in an organism with few endogenously occurring polyQ containing proteins, S. pombe, huntingtin with an expanded polyQ tract aggregates but is not toxic, in comparison to an established model of polyQ length-dependent huntingtin toxicity, S. cerevisiae, where it aggregates and is toxic and in which there are many endogenous polyQ proteins. I also demonstrate that the CAG nucleotide tracts within huntingtin are genetically stable in S. pombe, in contrast to their genetic instability in S. cerevisiae. Finally, I show the development of an immunoprecipitation protocol that will be used to study the Htt coimmunoprecipitating proteins from these different cellular microenvironments.

Chemical Modulators Of Protein Misfolding And Neurodegenerative Disease

Author: Pierfausto Seneci
Editor: Academic Press
ISBN: 012801959X
File Size: 39,53 MB
Format: PDF, ePub
Read: 391
Download

This book is a neurochemistry-based companion for Protein Misfolding and Neurodegenerative Diseases: Molecular Targets, an Elsevier title by the same author publishing in December 2014. While the first book focuses on biology and molecular targets, this companion book describes how these targets are regulated by small molecules and disease-modifying compounds. The book begins with a brief introduction to how key proteins become dysfunctional, and each subsequent chapter describes major disease mechanisms in Alzheimer’s and other tauopathies. Properties and development status of these molecular targets and disease mechanisms are thoroughly described, as are small molecule effectors of autophagy and dis-aggregating agents. Written to provide comprehensive coverage of neurodegenerative disease-modifying compounds Provides discipline-specific chapters that cover medicinal chemistry and clinical applications Provides an overview of more than 200 chemical classes and lead compounds, acting on selected molecular targets that are of relevance to any neurodegenerative disorder Coverage of misfolding diseases, chaperone proteins, ubiquitination and autophagy/oncology makes this book suitable for structural neurochemists, chemists, biologists, non-CNS scientists, and scientists interested in drug discovery

Protein Quality Control In Neurodegenerative Diseases

Author: Richard I. Morimoto
Editor: Springer Science & Business Media
ISBN: 3642279287
File Size: 53,82 MB
Format: PDF, ePub, Mobi
Read: 2728
Download

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.

Genotype Proteotype Phenotype Relationships In Neurodegenerative Diseases

Author: J. Cummings
Editor: Springer
ISBN: 9783540807803
File Size: 41,42 MB
Format: PDF, Docs
Read: 2767
Download

Recent advances in understanding the role of protein dysmetabolism in neurodegeneration was the theme of the Fondation IPSEN meeting addressing Genotype-Proteotype-Phenotype relationships. Experts from international laboratories contributed to the current volume to produce a comprehensive overview of the role of protein misfolding in neurodegeneration. Links between genotype and protein characteristics and between proteotype and clinical phenomenology were discussed across diseases categories. Progress in understanding the role of abnormalities of protein metabolism may lead to the identification of biological markers relevant to disease monitoring and to the development of new therapeutic agents capable of modifying and ameliorating basic neurodegenerative mechanisms.

Protein Misfolding In Alzheimer S And Other Age Related Neurodegenerative Diseases

Author:
Editor:
ISBN:
File Size: 27,40 MB
Format: PDF, Kindle
Read: 2603
Download


Heat Shock Proteins And The Brain Implications For Neurodegenerative Diseases And Neuroprotection

Author: Alexzander A.A. Asea
Editor: Springer Science & Business Media
ISBN: 9781402082313
File Size: 77,86 MB
Format: PDF, ePub
Read: 1624
Download

With the prevalence of neurodegenerative diseases on the rise as average life expectancy increases, the hunt for effective treatments and preventive measures for these disorders is a pressing challenge. Neurodegenerative disorders such as Alzheimer’s disease, Huntington’s disease, Parkinson’s disease and amyotrophic lateral sclerosis have been termed ‘protein misfolding disorders’ that are char- terized by the neural accumulation of protein aggregates. Manipulation of the cellular stress response involving the induction of heat shock proteins offers a the- peutic strategy to counter conformational changes in neural proteins that trigger pathogenic cascades resulting in neurodegenerative diseases. Heat shock proteins are protein repair agents that provide a line of defense against misfolded, aggregati- prone proteins. Heat Shock Proteins and the Brain: Implications for Neurodegenerative Diseases and Neuroprotection reviews current progress on neural heat shock proteins (HSP) in relation to neurodegenerative diseases (Part I), neuroprotection (Part II), ext- cellular HSP (Part III) and aging and control of life span (Part IV). Key basic and clinical research laboratories from major universities and hospitals around the world contribute chapters that review present research activity and importantly project the field into the future. The book is a must read for researchers, postdoctoral fellows and graduate students in the fields of Neuroscience, Neurodegenerative Diseases, Molecular Medicine, Aging, Physiology, Pharmacology and Pathology.

Protein Folding Disorders Of The Central Nervous System

Author: Ghiso Jorge A
Editor: World Scientific
ISBN: 9813222972
File Size: 68,85 MB
Format: PDF, ePub, Mobi
Read: 9268
Download

This exciting new book explores the dark side of the molecular protein assembly bringing an updated view of how failures in the homeostatic mechanisms that efficiently regulate protein folding leads to the accumulation of structurally abnormal pathogenic assemblies, encompassing an emerging group of diseases collectively known as "Protein Folding Disorders." This complex and diverse group of chronic and progressive entities are bridged together by their relationship to structural transitions in the native state of specific proteinaceous components, which for reasons poorly understood, convert into polymeric aggregates that generate poorly soluble tissue deposits and which are considered today the culprit of the disease pathogenesis in their respective diseases. Despite the diversity in the amino acid sequence of the different proteins involved in these heterogeneous disorders, all the pathologic conformers can trigger cascades of events ultimately resulting in cell dysfunction and death with devastating clinical consequences in many of the most precious aspects of human existence including personality, cognition, memory, and skilled movements. This book, which is composed of a compilation of chapters authored by outstanding and well-published scientists in the respective fields currently performing active investigations at world renowned universities and research centers, focuses on the growing number of diseases associated with protein misfolding in the central nervous system. Individual chapters are dedicated to the most common neurodegenerative diseases associated with protein aggregation/fibrillization focusing on the nature of the pathogenic species and the cellular pathways involved in the molecular pathogenesis of Alzheimer's, Parkinson's, and Huntington's diseases as well as in Amyotrophic Lateral Sclerosis, and Prion disorders. A group of contributions is centered on the current knowledge of the intracellular pathways and subcellular organelles affected by the different disease conditions, while others are focused in the emerging pathogenic role of misfolded subunits assembled into neurotoxic soluble oligomers, and in the novel notion of the transmissibility of the protein misfolded species, an innovative concept until recently only accepted for Prion diseases. Lastly, a different set of chapters is dedicated to the evaluation of novel therapeutic strategies for these devastating diseases. Contents: Misfolding, Aggregation, and Amyloid Formation: The Dark Side of Proteins (Agueda Rostagno and Jorge A Ghiso)Oligomers at the Synapse: Synaptic Dysfunction and Neurodegeneration (Emily Vogler, Matthew Mahavongtrakul, and Jorge Busciglio)Prion-Like Protein Seeding and the Pathobiology of Alzheimer's Disease (Lary C Walker)The Tau Misfolding Pathway to Dementia (Alejandra D Alonso, Leah S Cohen, and Viktoriya Morozova)The Biology and Pathobiology of α-Synuclein (Joel C Watts, Anurag Tandon, and Paul E Fraser)Impact of Loss of Proteostasis on Central Nervous System Disorders (Sentiljana Gumeni, Eleni N Tsakiri, Christina-Maria Cheimonidi, Zoi Evangelakou, Despoina Gianniou, Kostantinos Tallas, Eleni-Dimitra Papanagnou, Aimilia D Sklirou, and Ioannis P Trougakos)Protein Misfolding and Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis (Giovanni Manfredi and Hibiki Kawamata)Impact of Mitostasis and the Role of the Anti-Oxidant Responses on Central Nervous System Disorders (Sentiljana Gumeni, Eleni N Tsakiri, Christina-Maria Cheimonidi, Zoi Evangelakou, Despoina Gianniou, Kostantinos Tallas, Eleni-Dimitra Papanagnou, Aimilia D Sklirou, and Ioannis P Trougakos)Propagation of Misfolded Proteins in Neurodegeneration: Insights and Cautions from the Study of Prion Disease Prototypes (Robert C C Mercer, Nathalie Daude,

Folding For The Synapse

Author: Andreas Wyttenbach
Editor: Springer Science & Business Media
ISBN: 9781441970619
File Size: 45,71 MB
Format: PDF, Mobi
Read: 8345
Download

Folding for the Synapse addresses the current view on how protein folding and misfolding, controlled by molecular chaperones, contribute to synapse function and dysfunction. Molecular chaperones have been studied in relation to de novo protein folding, but there is increasing awareness that chaperone function is required for the regulation of protein dynamics when functioning physiologically as an isolated moiety or part of a protein complex. This book will introduce both important concepts of folding machineries and give examples of the biological relevance of further chaperone functions.