Amyloid deposition is a key pathological hallmark across a series of neurodegenerative diseases including Alzheimer's Disease, Parkinson's Disease and amyotrophic lateral sclerosis. Although the precise role of amyloids as causative triggers in neurodegeneration may be debatable, the structural conversions underlying the formation of amyloid oligomers and fibrils are critical events in disease pathophysiology. Such structural interconversions and protein self-assembly processes involve several proteins (such as amyloid, Tau, -synuclein, SOD1, or TDP-43) displaying distinct biochemical and structural properties but eventually aggregating into similar cross-beta fibrils.
Despite substantial breakthroughs achieved by Cryo-EM single-particle analysis of amyloid fibrils and their polymorphic variants, or advances on kinetic and analytic methods to quantitatively describe the complex chemical networks associated with the aggregation reaction, the field still lacks in-depth knowledge on the basis of molecular mechanisms as well as on the biological, physical and chemical processes behind amyloid protein aggregation. This knowledge is critical not only to establish the underlying basic biological processes related to amyloid aggregation in vivo, but also to envision the design of mechanism-based and/or structure-oriented therapeutics against amyloid-related diseases.
This Research Topic aims to collect high-quality Reviews and Original Research articles on the emerging research areas in the field listed below, with emphasis on the biochemical aspects of amyloid-related protein aggregation and its involvement in the molecular and cellular mechanisms underlying neurodegenerative diseases. We believe this field needs multidisciplinary approaches, and we thus encourage contributions including multi/interdisciplinary studies (e.g. chemistry, biochemistry, biophysics, molecular biology, structural biology, cellular biology, computational biology).
Priority topics to be covered include, but are not limited to, the following areas of the biochemistry of amyloids in neurodegenerative diseases:
· Investigations of amyloid oligomers and amyloid precursors
· Amyloid polymorphism
· Post-translational modifications and amyloid formation
· Phase transitions and protein aggregation in neurodegeneration
· Biological modulators of protein aggregation, including chaperones, metal ions and small molecules
· Molecular chaperones and protein interactions as physiological regulators of amyloid formation
· Surface-induced amyloid processes in neurodegeneration
· Cellular assays and other experimental models for protein aggregation and toxicity
· Quantitative approaches for mechanistic analysis of amyloid aggregation
· Structural studies of amyloid assemblies and protein self-assembly complexes
· Methods for the preparation and detection of amyloid and oligomers
· Bioimaging approaches for detection and spatial-temporal analysis of protein aggregation
Amyloid deposition is a key pathological hallmark across a series of neurodegenerative diseases including Alzheimer's Disease, Parkinson's Disease and amyotrophic lateral sclerosis. Although the precise role of amyloids as causative triggers in neurodegeneration may be debatable, the structural conversions underlying the formation of amyloid oligomers and fibrils are critical events in disease pathophysiology. Such structural interconversions and protein self-assembly processes involve several proteins (such as amyloid, Tau, -synuclein, SOD1, or TDP-43) displaying distinct biochemical and structural properties but eventually aggregating into similar cross-beta fibrils.
Despite substantial breakthroughs achieved by Cryo-EM single-particle analysis of amyloid fibrils and their polymorphic variants, or advances on kinetic and analytic methods to quantitatively describe the complex chemical networks associated with the aggregation reaction, the field still lacks in-depth knowledge on the basis of molecular mechanisms as well as on the biological, physical and chemical processes behind amyloid protein aggregation. This knowledge is critical not only to establish the underlying basic biological processes related to amyloid aggregation in vivo, but also to envision the design of mechanism-based and/or structure-oriented therapeutics against amyloid-related diseases.
This Research Topic aims to collect high-quality Reviews and Original Research articles on the emerging research areas in the field listed below, with emphasis on the biochemical aspects of amyloid-related protein aggregation and its involvement in the molecular and cellular mechanisms underlying neurodegenerative diseases. We believe this field needs multidisciplinary approaches, and we thus encourage contributions including multi/interdisciplinary studies (e.g. chemistry, biochemistry, biophysics, molecular biology, structural biology, cellular biology, computational biology).
Priority topics to be covered include, but are not limited to, the following areas of the biochemistry of amyloids in neurodegenerative diseases:
· Investigations of amyloid oligomers and amyloid precursors
· Amyloid polymorphism
· Post-translational modifications and amyloid formation
· Phase transitions and protein aggregation in neurodegeneration
· Biological modulators of protein aggregation, including chaperones, metal ions and small molecules
· Molecular chaperones and protein interactions as physiological regulators of amyloid formation
· Surface-induced amyloid processes in neurodegeneration
· Cellular assays and other experimental models for protein aggregation and toxicity
· Quantitative approaches for mechanistic analysis of amyloid aggregation
· Structural studies of amyloid assemblies and protein self-assembly complexes
· Methods for the preparation and detection of amyloid and oligomers
· Bioimaging approaches for detection and spatial-temporal analysis of protein aggregation