Dual functions of beta-amyloid oligomer and fibril in Cu(II)-induced H2O2 production.

摘要

Amyloid-beta (Abeta) aggregation and Cu(II)-related oxidative stress are involved in the dysfunction and death of neurons in Alzheimer's disease (AD). However, the relationship between Abeta and Cu(II) is not clear. Furthermore, the pro- or anti-oxidant properties of Abeta are also under great debate. Here the H2O2 generating ability of Abeta42 in its monomeric, oligomeric and fibrillar forms was studied in the presence of Cu(II). The results show that Abeta42 in both oligomeric and fibrillar forms can promote H2O2 generation at lower concentrations of Cu(II) and Abeta42 oligomer can promote H2O2 generation to a higher extent. Nevertheless, the promoting effect of Abeta42 oligomer and fibril may convert to an inhibitory effect when the concentration of Cu(II) is increased. This indicates the dual functions of Abeta42 oligomer and fibril in Cu(II)-induced H2O2 production. Hereby we present a new perspective on the roles of Abeta42 in Cu(II)-mediated oxidative stress and add new evidence to the viewpoint that Abeta42 oligomer may be primarily responsible for the pathogenesis of AD.