Permeabilization of Lipid Bilayers Is a Common Conformation-dependent Activity of Soluble Amyloid Oligomers in Protein Misfolding Diseases*

By R. Kayed, Y. Sokolov, B. Edmonds, Theresa M. McIntire, S. Milton, James E. Hall, C. Glabe. Journal of Biological Chemistry, 2004

871 citations recorded by the source corpus.

Amyloid fibrillization is multistep process involving soluble oligomeric intermediates, including spherical oligomers and protofibrils. Amyloid oligomers have a common, generic structure, and they are intrinsically toxic to cells, even when formed from non-disease related proteins, which implies they also share a common mechanism of pathogenesis and toxicity. Here we report that soluble oligomers from several types of amyloids specifically increase lipid bilayer conductance regardless of the sequence, while fibrils and soluble low molecular weight species have no effect. The increase in membrane conductance occurs without any evidence of discrete channel or pore formation or ion selectivity. The conductance is dependent on the concentration of oligomers and can be reversed by anti-oligomer antibody. These results indicate that soluble oligomers from many types of amyloidogenic proteins and peptides increase membrane conductance in a conformation-specific fashion and suggest that this may represent the common primary mechanism of pathogenesis in amyloid-related degenerative diseases.

Subfields: Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/a5ba6e79f71ede9112dcaaeea02253b46cfd09c8

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Citations in the corpus

Α-synuclein misfolding and Parkinson's disease. (2012, background): “Membrane permeation by amyloid oligomers without pore formation has also been proposed [98].”
Different Species of α-Synuclein Oligomers Induce Calcium Influx and Seeding (2007, background): “…than mature fibrils of -syn, are the pathogenic species (Conway et al., 2000; Goldberg and Lansbury, 2000; Masliah et al., 2000; Auluck et al., 2002; Bucciantini et al., 2002, 2004; Gosavi et al., 2002; Kayed et al., 2003, 2004; Park and Lansbury, 2003; Bodner et al., 2006; ElAgnaf et al., 2006).”
Alzheimer’s Disease and the β-Amyloid Peptide (2010, neutral): “Receptor-mediated effects are noted [98,99] as well as direct activity of oligomers on the membrane bilayer, especially at high ( µ M) concentrationswhich may stem from their surface activity.”