Amyloid-ß-peptide reduces copper(II) to copper(I) independent of its aggregation state

• CARLOS OPAZO ; FRANCISCA H RUIZ ; NIBALDO C INESTROSA ^[1]
  1. [1] Pontificia Universidad Católica de Chile

     Pontificia Universidad Católica de Chile

     Santiago, Chile

     
• Localización: Biological Research, ISSN-e 0717-6287, ISSN 0716-9760, Vol. 33, Nº. 2, 2000, págs. 125-131
• Idioma: inglés
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• Resumen

  • Alzheimer’s disease (AD) is characterized by the deposition of amyloid b-peptide (Aß) 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 Aß 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-ß-peptide on copper reduction. In independent experiments we measured the copper-reducing ability of soluble and fibrillar Aß1-40 forms by bathocuproine assays. As it was previously observed for the amyloid precursor protein (APP), the Aß peptide showed copper-reducing ability. The capacity of Aß to reduce copper was independent of the aggregation state. Finally, the Aß peptide derived from the human sequence has a greater effect than the Aß peptide derived from the rat sequence, suggesting that histidine 13 may play a role in copper reduction. In agreement with this possibility, the Aß peptide reduces less copper in the presence of exogenous histidine