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

FEBS Lett. 2015 Oct 24;589(21):3228-36. doi: 10.1016/j.febslet.2015.09.027. Epub 2015 Oct 10.

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.

Keywords: Alzheimer’s disease; Amyloid-β Peptide; Europium; GM1 ganglioside; Permeation inhibition; Protein misfolding.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / antagonists & inhibitors*
  • Cell Membrane Permeability / drug effects*
  • Europium / pharmacokinetics*
  • Europium / pharmacology
  • G(M1) Ganglioside / metabolism
  • Lipid Bilayers / chemistry
  • Spectrometry, Fluorescence
  • Surface Plasmon Resonance

Substances

  • Amyloid beta-Peptides
  • Lipid Bilayers
  • G(M1) Ganglioside
  • Europium