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Journal article
A beta 42 oligomers, but not fibrils, simultaneously bind to and cause damage to ganglioside-containing lipid membranes
Biochemical journal, v 439
01 Oct 2011
PMID: 21702743
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
A beta (amyloid-beta peptide) assembles to form amyloid fibres that accumulate in senile plaques associated with AD (Alzheimer's disease). The major constituent, a 42-residue A beta, has the propensity to assemble and form soluble and potentially cytotoxic oligomers, as well as ordered stable amyloid fibres. It is widely believed that the cytotoxicity is a result of the formation of transient soluble oligomers. This observed toxicity may be associated with the ability of oligomers to associate with and cause permeation of lipid membranes. In the present study, we have investigated the ability of oligomeric and fibrillar A beta 42 to simultaneously associate with and affect the integrity of biomimetic membranes in vitro. Surface plasmon field-enhanced fluorescence spectroscopy reveals that the binding of the freshly dissolved oligomeric 42-residue peptide binds with a two-step association with the lipid bilayer, and causes disruption of the membrane resulting in leakage from vesicles. In contrast, fibrils bind with a 2-fold reduced avidity, and their addition results in approximately 2-fold less fluorophore leakage compared with oligomeric A beta. Binding of the oligomers may be, in part, mediated by the GM1 ganglioside receptors as there is a 1.8-fold increase in oligomeric A beta binding and a 2-fold increase in permeation compared with when GM1 is not present. Atomic force microscopy reveals the formation of defects and holes in response to oligomeric A beta, but not preformed fibrillar A beta. The results of the present study indicate that significant membrane disruption arises from association of low-molecular-mass A beta and this may be mediated by mechanical damage to the membranes by A beta aggregation. This membrane disruption may play a key role in the mechanism of A beta-related cell toxicity in AD.
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Details
- Title
- A beta 42 oligomers, but not fibrils, simultaneously bind to and cause damage to ganglioside-containing lipid membranes
- Creators
- Thomas L. Williams - Univ Sussex, Sch Life Sci, Falmer BN1 9QG, E Sussex, EnglandBenjamin R. G. Johnson - University of LeedsBrigita Urbanc - Drexel UniversityA. Toby A. Jenkins - University of BathSimon D. A. Connell - University of LeedsLouise C. Serpell - University of Sussex
- Publication Details
- Biochemical journal, v 439
- Publisher
- Portland Press Ltd
- Number of pages
- 11
- Grant note
- ART-PG2007-3 / Alzheimers Research UK; Alzheimer's Research UK (ARUK) A6027818 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Alzheimer's Research UK (previously Alzheimer's Research Trust)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Physics
- Web of Science ID
- WOS:000295767100007
- Scopus ID
- 2-s2.0-80052747064
- Other Identifier
- 991019169651404721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology