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.

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.

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.

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

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.

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

Current research suggests that neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, and Creutzfeldt-Jacob may be linked to disorders in protein shape referred to as protein misfolding. Continued study in this area could lead to promising advances in future treatment of these diseases. This groundbreaking text describes the latest findings regarding protein misfolding in the context of it being a marker, and perhaps a cause, in neurodegenerative diseases. Comprehensive coverage includes the diverse biochemical targets/markers for each disease, the currently limited success of drug therapies, and the cutting-edge research that could lead to more promising treatments.