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; Louise C. Serpell

doi:10.1016/j.febslet.2015.09.027

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, Louise C. Serpell

Research output: Contribution to journal › Article › peer-review

9 Citations (SciVal)

Abstract

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.

Original language	English
Pages (from-to)	3228-3236
Number of pages	9
Journal	FEBS Letters
Volume	589
Issue number	21
DOIs	https://doi.org/10.1016/j.febslet.2015.09.027
Publication status	Published - 24 Oct 2015

Keywords

Alzheimer's disease
Amyloid-β Peptide
Europium
GM1 ganglioside
Permeation inhibition
Protein misfolding

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10.1016/j.febslet.2015.09.027

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title = "Europium as an inhibitor of Amyloid-β(1-42) induced membrane permeation",

abstract = "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.",

keywords = "Alzheimer's disease, Amyloid-β Peptide, Europium, GM1 ganglioside, Permeation inhibition, Protein misfolding",

author = "Williams, {Thomas L.} and Brigita Urbanc and Marshall, {Karen E.} and Vadukul, {Devkee M.} and Jenkins, {A. Toby A} and Serpell, {Louise C.}",

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AU - Williams, Thomas L.

AU - Urbanc, Brigita

AU - Marshall, Karen E.

AU - Vadukul, Devkee M.

AU - Jenkins, A. Toby A

AU - Serpell, Louise C.

PY - 2015/10/24

Y1 - 2015/10/24

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - Amyloid-β Peptide

KW - Europium

KW - GM1 ganglioside

KW - Permeation inhibition

KW - Protein misfolding

UR - http://www.scopus.com/inward/record.url?scp=84944930612&partnerID=8YFLogxK

UR - http://dx.doi.org/10.1016/j.febslet.2015.09.027

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DO - 10.1016/j.febslet.2015.09.027

M3 - Article

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EP - 3236

JO - FEBS Letters

JF - FEBS Letters

IS - 21

ER -

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

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Keywords

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