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

25 Citations (Scopus)

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

Poloxamer
Amyloid
Membranes
Cell Membrane Permeability
Aptitude
Lipid Bilayers
Type 2 Diabetes Mellitus
Alzheimer Disease
Polymers
Membrane Proteins
Cell Death
In Vitro Techniques

Keywords

  • amyloid
  • membrane
  • oligomers
  • P188
  • toxicity

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Poloxamer 188 Copolymer Membrane Sealant Rescues Toxicity of Amyloid Oligomers In Vitro. / Mina, Erene W.; Lasagna-Reeves, Cristian; Glabe, Charles G.; Kayed, Rakez.

In: Journal of Molecular Biology, Vol. 391, No. 3, 21.08.2009, p. 577-585.

Research output: Contribution to journalArticle

Mina, Erene W. ; Lasagna-Reeves, Cristian ; Glabe, Charles G. ; Kayed, Rakez. / Poloxamer 188 Copolymer Membrane Sealant Rescues Toxicity of Amyloid Oligomers In Vitro. In: Journal of Molecular Biology. 2009 ; Vol. 391, No. 3. pp. 577-585.
@article{d7fcbeea707549cb91e561360c9532b7,
title = "Poloxamer 188 Copolymer Membrane Sealant Rescues Toxicity of Amyloid Oligomers In Vitro",
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.",
keywords = "amyloid, membrane, oligomers, P188, toxicity",
author = "Mina, {Erene W.} and Cristian Lasagna-Reeves and Glabe, {Charles G.} and Rakez Kayed",
year = "2009",
month = "8",
day = "21",
doi = "10.1016/j.jmb.2009.06.024",
language = "English (US)",
volume = "391",
pages = "577--585",
journal = "Journal of Molecular Biology",
issn = "0022-2836",
publisher = "Academic Press Inc.",
number = "3",

}

TY - JOUR

T1 - Poloxamer 188 Copolymer Membrane Sealant Rescues Toxicity of Amyloid Oligomers In Vitro

AU - Mina, Erene W.

AU - Lasagna-Reeves, Cristian

AU - Glabe, Charles G.

AU - Kayed, Rakez

PY - 2009/8/21

Y1 - 2009/8/21

N2 - 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.

AB - 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.

KW - amyloid

KW - membrane

KW - oligomers

KW - P188

KW - toxicity

UR - http://www.scopus.com/inward/record.url?scp=67651149466&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67651149466&partnerID=8YFLogxK

U2 - 10.1016/j.jmb.2009.06.024

DO - 10.1016/j.jmb.2009.06.024

M3 - Article

VL - 391

SP - 577

EP - 585

JO - Journal of Molecular Biology

JF - Journal of Molecular Biology

SN - 0022-2836

IS - 3

ER -