Ebook: Protein Folding and Misfolding: Neurodegenerative Diseases
- Tags: Biomedicine general, Molecular Medicine, Neurosciences, Cell Biology, Medical Biochemistry, Neurobiology
- Series: Focus on Structural Biology 7
- Year: 2009
- Publisher: Springer Netherlands
- Edition: 1
- Language: English
- pdf
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.
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.
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.
Content:
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 ?-Synuclein Aggregation by Antioxidants and Chaperones in Parkinson’s Disease....Pages 175-206
Novel Proteins in ?-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
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.
Content:
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 ?-Synuclein Aggregation by Antioxidants and Chaperones in Parkinson’s Disease....Pages 175-206
Novel Proteins in ?-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
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