Protein Misfolding Diseases

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.

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.

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For decades it has been known that structured conformations are important for the proper functioning of most cellular proteins. However, appreciation that protein folding to the functional conformations as well as the structural maintenance of protein molecules are very complex processes has only emerged during the last ten years. The intimate interplay uncovered by this scientific development led us to realize that perturbations of the protein folding process and disturbances of conformational maintenance are major disease mechanisms. This development has given rise to the concept of conformational diseases and the broader signature of protein folding diseases, comprising diseases in which mutations or environmental stresses may result in a partial misfolding that leads then to alternative conformations capable of disturbing cellular processes. This may happen by self-association (aggregation), as in prion and Alzheimer’s diseases, or by incorporation of alternatively folded subunits into structural entities, as in collagen diseases. Another possibility is that folding to the native structure is impaired or abolished, resulting in decreased stea- state levels of the correctly folded protein, as is observed in cystic fibrosis and 1-antitrypsin deficiency, as well as in many enzyme deficiencies. In addition, deficiencies of proteins that are engaged in assisting and supervising protein folding (protein quality control) may impair the folding of many other proteins, resulting in pathological phenotypes. Examples of this are the spastic paraplegia attributable to mutations in mitochondrial protease/chaperone complexes.

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.

Bio-Nanoimaging: Protein Misfolding & Aggregation provides a unique introduction to both novel and established nanoimaging techniques for visualization and characterization of misfolded and aggregated protein species. The book is divided into three sections covering: - Nanotechnology and nanoimaging technology, including cryoelectron microscopy of beta(2)-microglobulin, studying amyloidogensis by FRET; and scanning tunneling microscopy of protein deposits - Polymorphisms of protein misfolded and aggregated species, including fibrillar polymorphism, amyloid-like protofibrils, and insulin oligomers - Polymorphisms of misfolding and aggregation processes, including multiple pathways of lysozyme aggregation, misfolded intermediate of a PDZ domain, and micelle formation by human islet amyloid polypeptide Protein misfolding and aggregation is a fast-growing frontier in molecular medicine and protein chemistry. Related disorders include cataracts, arthritis, cystic fibrosis, late-onset diabetes mellitus, and numerous neurodegenerative diseases like Alzheimer's and Parkinson's. Nanoimaging technology has proved crucial in understanding protein-misfolding pathologies and in potential drug design aimed at the inhibition or reversal of protein aggregation. Using these technologies, researchers can monitor the aggregation process, visualize protein aggregates and analyze their properties. Provides practical examples of nanoimaging research from leading molecular biology, cell biology, protein chemistry, biotechnology, genetics, and pharmaceutical labs Includes over 200 color images to illustrate the power of various nanoimaging technologies Focuses on nanoimaging techniques applied to protein misfolding and aggregation in molecular medicine

Protein misfolding is a key feature of many disorders in humans, given that over twenty proteins are known to misfold and cause disease. In Protein Folding, Misfolding, and Disease: Methods and Protocols, experts in the field present a collection of current methods for studying the analysis of protein folding and misfolding, featuring strategies for expressing and refolding recombinant proteins which can then be utilized in subsequent experiments. This detailed volume also covers methods for analyzing the formation of amyloid, protocols for determining the size and structure of native and misfolded proteins, as well as specific examples of where misfolded proteins can be examined using state-of –the-art technologies. Written in the highly successful Methods in Molecular BiologyTM series format, chapters contain introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Up to date and authoritative, Protein Folding, Misfolding, and Disease: Methods and Protocols offers researchers the tools necessary to move ahead in this vital field.

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.