Transition metal-mediated glycoxidation accelerates cross-linking of beta-amyloid peptide.
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.
Loske
C
C
Physiological Chemistry I, Biocenter, University of Würzburg, Germany.
Gerdemann
A
A
Schepl
W
W
Wycislo
M
M
Schinzel
R
R
Palm
D
D
Riederer
P
P
Münch
G
G
D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000975:Antioxidants / Q000494:pharmacology; D017127:Glycation End Products, Advanced / Q000502:physiology*; D006031:Glycosylation; D006801:Humans; D008670:Metals / Q000494:pharmacology*; D010710:Phosphates / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D017127:Glycation End Products, Advanced; D008670:Metals; D010710:Phosphates