Soluble amyloid β1-28-copper(I)/copper(II)/iron(II) complexes are potent antioxidants in cell-free systems

Rozena Baruch-Suchodolsky, Bilha Fischer

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Amyloid β (Aβ) is a central characteristic of Alzheimer's disease (AD). Currently, there is a long-standing dispute regarding the role of Aβ-metal ion (Zn, Cu, and Fe) complexes in AD pathogenesis. Here, we aim to decipher the connection between oxidative damage implicated in AD and Aβ-metal ion complexes. For this purpose we study, using ESR, the modulation of Cu/Fe-induced H2O2 decomposition by Aβ1-28 (Aβ28), a soluble model of Aβ40/42. The addition of H2O2 to 0.6 nM-360 μM Aβ28 solutions containing 100 μM Cu(II)/Cu(I)/Fe(II) at pH 6.6 results in a concentration-dependent sigmoidal decay of [·OH] with IC50 values of 61, 59, and 84 μM, respectively. Furthermore, Aβ28 reduces 90% of ·OH production rate in the Cu(I)-H2O2 system in 5 min. Unlike soluble Aβ28, Aβ28-Cu aggregates exhibit poor antioxidant activity. The mode of antioxidant activity of soluble Aβ28 is twofold. The primary (rapid) mechanism involves metal chelation, whereas the secondary (slow) mechanism involves OH scavenging and oxidation of Cu(Fe)-coordinating ligands. On the basis of our findings, we propose that soluble Aβ may play a protective role in the early stages of AD, but not in healthy individuals, where Aβ' s concentration is nanomolar. Yet, when Aβ-metal ion complexes undergo aggregation, they significantly lose their protective function and allow oxidative damage to occur.

Original languageEnglish
Pages (from-to)7796-7806
Number of pages11
JournalBiochemistry
Volume47
Issue number30
DOIs
StatePublished - 29 Jul 2008

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