Poloxamer 188 Copolymer Membrane Sealant Rescues Toxicity of Amyloid Oligomers In Vitro

Erene W. Mina, Cristian Lasagna-Reeves, Charles G. Glabe, Rakez Kayed

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)577-585
Number of pages9
JournalJournal of Molecular Biology
Volume391
Issue number3
DOIs
StatePublished - Aug 21 2009

    Fingerprint

Keywords

  • P188
  • amyloid
  • membrane
  • oligomers
  • toxicity

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this