Amyloid-beta-peptide reduces copper(II) to copper(I) independent of its aggregation state.
Alzheimer's disease (AD) is characterized by the deposition of amyloid beta-peptide (A beta) and neuronal degeneration in brain regions involved in learning and memory. One of the leading etiologic hypotheses regarding AD is the involvement of free radical-mediated oxidative stress in neuronal degeneration. Recent evidence suggests that metals concentrated in amyloid deposits may contribute to the oxidative insults observed in AD-affected brains. We hypothesized that A beta peptide in the presence of copper enhances its neurotoxicity generating free radicals via copper reduction. In the present study, we have examined the effect of the aggregation state of amyloid-beta-peptide on copper reduction. In independent experiments we measured the copper-reducing ability of soluble and fibrillar A beta(1-40) forms by bathocuproine assays. As it was previously observed for the amyloid precursor protein (APP), the A beta peptide showed copper-reducing ability. The capacity of A beta to reduce copper was independent of the aggregation state. Finally, the A beta peptide derived from the human sequence has a greater effect than the A beta peptide derived from the rat sequence, suggesting that histidine 13 may play a role in copper reduction. In agreement with this possibility, the A beta peptide reduces less copper in the presence of exogenous histidine.
Opazo
C
C
Centro de Regulación Celular y Patología, Departamento de Biología Celular y Molecular, Pontificia Universidad Católica de Chile, Santiago.
Ruiz
F H
FH
Inestrosa
N C
NC
D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D003300:Copper / Q000378:metabolism*; D006801:Humans; D015227:Lipid Peroxidation / Q000502:physiology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D003300:Copper