Protein folding and misfolding: neurodegenerative diseases (Focus on Structural Biology Book 7)

The worldwide increasing age of populations brought the neurodegenerative diseases into the focus of interest. A number of the diverse human neurodegenerative diseases are now recognized as conformational diseases frequently caused by aggregations of unfolded or misfolded proteins. Knowledge on the intrinsically unstructured proteins, a new family of gene products as well as on the misfolded proteins produced by genetic mutation or environmental effects has been extensively accumulated in the past years. These proteins frequently cause proteolytic stress and/ or enter into aberrant, non-physiological protein-protein interactions leading to sequestration of protein aggregates which are assemblies of many not-yet-identified components in addition to the deposition of well-characterized misfolded peptides and proteins such as b-amyloid, tau, a-synuclein and polyglutamine containing proteins. These protein assemblies display diverse ultrastructures such aggresomes, fibers, oligomers or amorphous structures, however, the nature of these species concerning their cytoprotective or cytotoxic effects has not been clarified yet. The main focus of this volume is to review the molecular events initiated by unfolded or misfolded proteins leading to conformational human diseases, with special emphasis on the macromolecular homo- and heteroassociations of the malfolded proteins into characteristic ultrastructures found primarily in Parkinson’s and Alzheimer’s diseases. This book reviews the structural knowledge accumulated for well-studied and for newly discovered proteins involved in paradigmatic conformational disorders with the aim to broaden our understanding of the pathomechanisms of neurodegeneration, which is crucial for finding effective therapeutic interventions that could prevent or circumvent the development of neurodegenerative disorders in humans. Front Matter....Pages I-XIII Structural Disorder and Its Connection with Misfolding Diseases....Pages 1-19 Intrinsic Disorder in Proteins Associated with Neurodegenerative Diseases....Pages 21-75 Dynamic Role of Ubiquitination in the Management of Misfolded Proteins Associated with Neurodegenerative Diseases....Pages 77-95 Protein Misfolding and Axonal Protection in Neurodegenerative Diseases....Pages 97-110 Endoplasmic Reticulum Stress in Neurodegeneration....Pages 111-132 Involvement of Alpha-2 Domain in Prion Protein Conformationally-Induced Diseases....Pages 133-157 Synuclein Structure and Function in Parkinson’s Disease....Pages 159-174 Inhibition of α-Synuclein Aggregation by Antioxidants and Chaperones in Parkinson’s Disease....Pages 175-206 Novel Proteins in α-Synucleinopathies....Pages 207-224 TPPP/p25: A New Unstructured Protein Hallmarking Synucleinopathies....Pages 225-250 Protein-Based Neuropathology and Molecular Classification of Human Neurodegenerative Diseases....Pages 251-272 Back Matter....Pages 273-277 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.