Transition metal-mediated glycoxidation accelerates cross-linking of beta-amyloid peptide

Eur J Biochem. 2000 Jul;267(13):4171-8. doi: 10.1046/j.1432-1327.2000.01452.x.

Abstract

beta-Amyloid deposits, hallmarks of Alzheimer's disease, contain both sugar-derived 'advanced glycation end products' (AGEs) and copper and iron ions. Our in vitro experiments using synthetic beta-amyloid peptide and glucose or fructose show that formation of covalently cross-linked high-molecular-mass beta-amyloid peptide oligomers is accelerated by micromolar amounts of copper (Cu+, Cu2+) and iron (Fe2+, Fe3+) ions. Formation of these covalent AGE cross-links can be inhibited by capping agents of amino groups, redox-inactive metal chelators and antioxidants, suggesting that these drugs may be able to slow down the formation of insoluble beta-amyloid deposits in vivo and possibly the progression of Alzheimer's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / metabolism*
  • Antioxidants / pharmacology
  • Glycation End Products, Advanced / physiology*
  • Glycosylation
  • Humans
  • Metals / pharmacology*
  • Phosphates / pharmacology

Substances

  • Amyloid beta-Peptides
  • Antioxidants
  • Glycation End Products, Advanced
  • Metals
  • Phosphates