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 (Eu(3+)), 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 Eu(3+) inhibits Aβ42-membrane interactions and this may lead to protection of membrane integrity against Aβ42 induced toxicity.
authors.affiliation: School of Life Sciences, University of Sussex, Falmer, East Sussex BN1 9QG, UK; Physics Department, Drexel University, Philadelphia, PA 19104, USA; School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. Electronic address: tw200682@gmail.com.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Williams
authors.affiliation: Physics Department, Drexel University, Philadelphia, PA 19104, USA.
authors.forename: Brigita
authors.initials: B
authors.lastname: Urbanc
authors.affiliation: School of Life Sciences, University of Sussex, Falmer, East Sussex BN1 9QG, UK.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Marshall
authors.affiliation: School of Life Sciences, University of Sussex, Falmer, East Sussex BN1 9QG, UK.
authors.forename: Devkee M
authors.initials: DM
authors.lastname: Vadukul
authors.affiliation: Department of Chemistry, University of Bath, Bath BA2 7AY, UK.
authors.forename: A Toby A
authors.initials: AT
authors.lastname: Jenkins
authors.affiliation: School of Life Sciences, University of Sussex, Falmer, East Sussex BN1 9QG, UK. Electronic address: L.C.Serpell@sussex.ac.uk.
authors.forename: Louise C
authors.initials: LC
authors.lastname: Serpell
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors*; D002463:Cell Membrane Permeability / Q000187:drug effects*; D005063:Europium / Q000493:pharmacokinetics* / Q000494:pharmacology; D005677:G(M1) Ganglioside / Q000378:metabolism; D008051:Lipid Bilayers / Q000737:chemistry; D013050:Spectrometry, Fluorescence; D020349:Surface Plasmon Resonance
chemical_list: D016229:Amyloid beta-Peptides; D008051:Lipid Bilayers; D005677:G(M1) Ganglioside; D005063:Europium
keywords: Alzheimer’s disease; Amyloid-β Peptide; Europium; GM1 ganglioside; Permeation inhibition; Protein misfolding