Inhibitory effect of human serum albumin on Cu-induced Aβ40 aggregation and toxicity

It has been suggested that the aggregation and cytotoxicity of amyloid-beta (A beta) peptide with transition-metal ions in neuronal cells is involved in the development and progression of Alzheimer's disease (AD). As the most abundant protein in blood plasma and in cerebrospinal fluid, human serum albumin (HSA) can bind A beta in vivo and subsequently inhibit A beta fibril growth. However, the roles of albumin in Cu-induced A beta aggregation and toxicity, and its potential biological relevance to AD therapy, were not stressed enough. Here, we showed that HSA was capable of binding Cu (I) with much higher affinity than A beta, competitively inhibiting the interaction of A beta and Cu ions. In the presence of biological reducing agent ascorbate, HSA inhibited Cu (II)/Cu (I)-mediated A beta(40) aggregation, reactive oxygen species production, and neurotoxicity. However, in the absence of Cu (II)/Cu (I), HSA could not effectively inhibit A beta(40) aggregation and neurotoxicity at 24 h (or less) incubation time, but decreased A beta(40) aggregation at much longer incubation (120 h). Our data suggested that through competitively decreasing Cu-A beta interaction, HSA could effectively inhibit Cu (II)/Cu (I)-induced A beta(40) aggregation and neurotoxicity, and play important roles in regulating redox balance as well as metal homeostasis in AD prevention and therapy. (C) 2015 Elsevier B.V. All rights reserved.