Metal binding to the amyloid-β peptides in the presence of biomembranes: potential mechanisms of cell toxicity

J Biol Inorg Chem. 2019 Dec;24(8):1189-1196. doi: 10.1007/s00775-019-01723-9. Epub 2019 Sep 27.

Abstract

The amyloid-β (Aβ) peptides are key molecules in Alzheimer's disease (AD) pathology. They interact with cellular membranes, and can bind metal ions outside the membrane. Certain oligomeric Aβ aggregates are known to induce membrane perturbations and the structure of these oligomers-and their membrane-perturbing effects-can be modulated by metal ion binding. If the bound metal ions are redox active, as e.g., Cu and Fe ions are, they will generate harmful reactive oxygen species (ROS) just outside the membrane surface. Thus, the membrane damage incurred by toxic Aβ oligomers is likely aggravated when redox-active metal ions are present. The combined interactions between Aβ oligomers, metal ions, and biomembranes may be responsible for at least some of the neuronal death in AD patients.

Keywords: Amyloid disease; Amyloid-beta peptide; Cytotoxicity; Membrane pore; Phospholipid membrane; Reactive oxygen species; Redox-active metal ion.

Publication types

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

MeSH terms

  • Alzheimer Disease / metabolism
  • Amino Acid Sequence
  • Amyloid beta-Peptides / metabolism*
  • Cell Membrane / metabolism*
  • Copper / chemistry
  • Copper / metabolism*
  • Humans
  • Iron / chemistry
  • Iron / metabolism*
  • Protein Binding
  • Reactive Oxygen Species / chemistry
  • Reactive Oxygen Species / metabolism

Substances

  • Amyloid beta-Peptides
  • Reactive Oxygen Species
  • Copper
  • Iron