Channel formation in planar lipid bilayers by a neurotoxic fragment of the beta-amyloid peptide

Biochem Biophys Res Commun. 1994 Jul 29;202(2):1142-8. doi: 10.1006/bbrc.1994.2047.

Abstract

Alzheimer's disease (AD) pathology is characterized by plaques, tangles, and neuronal cell loss. The main constituent of plaques is beta-amyloid peptide (A beta), a 39-42 residue peptide which has been linked to disruption of calcium homeostasis and neurotoxicity in vitro. We demonstrate that a neurotoxic fragment of A beta, A beta (25-35) spontaneously inserted into planar lipid membranes to form weakly selective, voltage dependent, ion-permeable channels. We suggest that channel formation may be involved in the pathogenesis of AD and that A beta (25-35) may be the active channel forming segment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Amyloid beta-Peptides / chemistry
  • Amyloid beta-Peptides / metabolism*
  • Calcium / metabolism
  • Chlorides / metabolism
  • Humans
  • Ion Channels / metabolism*
  • Lipid Bilayers / metabolism*
  • Membrane Potentials
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism*
  • Potassium / metabolism
  • Sodium / metabolism

Substances

  • Amyloid beta-Peptides
  • Chlorides
  • Ion Channels
  • Lipid Bilayers
  • Peptide Fragments
  • Sodium
  • Potassium
  • Calcium