Common structure and toxic function of amyloid oligomers implies a common mechanism of pathogenesis.
Recent findings indicate that soluble amyloid oligomers may represent the primary pathologic species in degenerative diseases. These amyloid oligomers share common structural features and the ability to permeabilize membranes, suggesting that they also share a common primary mechanism of pathogenesis. Membrane permeabilization by amyloid oligomers may initiate a common group of downstream pathologic processes, including intracellular calcium dyshomeostasis, production of reactive oxygen species, altered signaling pathways, and mitochondrial dysfunction that represent key effectors of cellular dysfunction and cell death in amyloid-associated degenerative disease, such as sporadic inclusion-body myositis.
Glabe
Charles G
CG
Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA. cglabe@uci.edu
Kayed
Rakez
R
D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism; D000682:Amyloid / Q000737:chemistry / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000276:immunology; D000686:Amyloidosis / Q000209:etiology / Q000378:metabolism; D000818:Animals; D000918:Antibody Specificity; D001704:Biopolymers; D002118:Calcium / Q000378:metabolism; D002463:Cell Membrane Permeability; D003704:Dementia / Q000209:etiology / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D006816:Huntington Disease / Q000209:etiology / Q000378:metabolism; D002479:Inclusion Bodies / Q000737:chemistry; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000502:physiology; D018979:Myositis, Inclusion Body / Q000209:etiology / Q000378:metabolism; D010300:Parkinson Disease / Q000209:etiology / Q000378:metabolism; D017510:Protein Folding; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D012995:Solubility; D013329:Structure-Activity Relationship
D000682:Amyloid; D016229:Amyloid beta-Peptides; D001704:Biopolymers; D017382:Reactive Oxygen Species; D002118:Calcium