Elucidating Amyloid β-Protein Folding and Assembly:  A Multidisciplinary Approach

Oligomeric, neurotoxic amyloid protein assemblies are thought to be causative agents in Alzheimer's and other neurodegenerative diseases. Development of oligomer-specific therapeutic agents requires a mechanistic understanding of the oligomerization process. This is a daunting task because amyl...

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Bibliographic Details
Published in:Accounts of chemical research 2006-09, Vol.39 (9), p.635-645
Main Authors: Teplow, David B, Lazo, Noel D, Bitan, Gal, Bernstein, Summer, Wyttenbach, Thomas, Bowers, Michael T, Baumketner, Andrij, Shea, Joan-Emma, Urbanc, Brigita, Cruz, Luis, Borreguero, Jose, Stanley, H. Eugene
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Amyloid beta-Peptides - chemistry
Models, Molecular
Molecular Sequence Data
Protein Conformation
Protein Folding
Thermodynamics
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Summary:Oligomeric, neurotoxic amyloid protein assemblies are thought to be causative agents in Alzheimer's and other neurodegenerative diseases. Development of oligomer-specific therapeutic agents requires a mechanistic understanding of the oligomerization process. This is a daunting task because amyloidogenic protein oligomers often are metastable and comprise structurally heterogeneous populations in equilibrium with monomers and fibrils. A single methodological approach cannot elucidate the entire protein assembly process. An integrated multidisciplinary program is required. We discuss here the synergistic application of in hydro, in vacuo, and in silico methods to the study of the amyloid β-protein, the key pathogenetic agent in Alzheimer's disease.
ISSN:0001-4842
1520-4898
DOI:10.1021/ar050063s