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Europium as an inhibitor of Amyloid-β(1-42) induced membrane permeation
Journal article   Open access   Peer reviewed

Europium as an inhibitor of Amyloid-β(1-42) induced membrane permeation

Thomas L Williams, Brigita Urbanc, Karen E Marshall, Devkee M Vadukul, A. Toby A Jenkins and Louise C Serpell
FEBS letters, v 589(21), pp 3228-3236
24 Oct 2015
PMID: 26450778
url
https://doi.org/10.1016/j.febslet.2015.09.027View
Published, Version of Record (VoR) Open

Abstract

GM1 ganglioside Amyloid-β Peptide Protein misfolding Alzheimer’s disease Permeation inhibition Europium
[Display omitted] •Europium ions complex with GM1 gangliosides in phospholipid membranes.•Europium ions cause inhibition Aβ–membrane interactions.•Europium blocks an Aβ receptor protecting against membrane permeation.•Discrete Aβ binding events correlate to specific membrane permeation events. Soluble Amyloid-beta (Aβ) oligomers are a source of cytotoxicity in Alzheimer’s disease (AD). The toxicity of Aβ oligomers may arise from their ability to interact with and disrupt cellular membranes mediated by GM1 ganglioside receptors within these membranes. Therefore, inhibition of Aβ–membrane interactions could provide a means of preventing the toxicity associated with Aβ. Here, using Surface Plasmon field-enhanced Fluorescence Spectroscopy, we determine that the lanthanide, Europium III chloride (Eu3+), strongly binds to GM1 ganglioside-containing membranes and prevents the interaction with Aβ42 leading to a loss of the peptides ability to cause membrane permeation. Here we discuss the molecular mechanism by which Eu3+ inhibits Aβ42-membrane interactions and this may lead to protection of membrane integrity against Aβ42 induced toxicity.

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Biochemistry & Molecular Biology
Biophysics
Cell Biology
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