Poloxamer 188 copolymer membrane sealant rescues toxicity of amyloid oligomers in vitro.
Amyloid oligomers and protofibrils increase cell membrane permeability, eventually leading to cell death. Here, we demonstrate that amyloid oligomer toxicity and membrane permeabilization can be reversed using the membrane sealant copolymer poloxamer 188. The data indicate that amyloid oligomer toxicity is caused by defects in the lipid bilayer of the type that are sealed by poloxamer 188. Our results also suggest the possibility of using polymer-based membrane sealants to prevent or reverse amyloid oligomer toxicity in vivo. Because the ability to permeabilize membranes is a generic property of amyloid oligomers, this therapeutic approach may be effective for the treatment of many degenerative diseases caused in part by the interaction of misfolded proteins with cell membranes, as in Alzheimer's disease, type II diabetes, and a host of others.
Mina
Erene W
EW
Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697-3900, USA.
Lasagna-Reeves
Cristian
C
Glabe
Charles G
CG
Kayed
Rakez
R
D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000633:toxicity; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D002463:Cell Membrane Permeability; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008051:Lipid Bilayers / Q000378:metabolism; D008560:Membrane Fluidity; D009842:Oligopeptides / Q000633:toxicity*; D020442:Poloxamer / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D008051:Lipid Bilayers; D009842:Oligopeptides; D020442:Poloxamer