Disaggregation ability of different chelating molecules on copper ion-triggered amyloid fibers.

ABSTRACT

Dysfunctional interaction of amyloid-ß (Aß) with excess metal ions is proved to be related to the etiology of Alzheimer's disease (AD). Using metal-binding compounds to reverse metal-triggered Aß aggregation has become one of the potential therapies for AD. In this study, the ability of a carboxylic acid gemini surfactant (SDUC), a widely used metal chelator (EDTA), and an antifungal drug clioquinol (CQ) in reversing the Cu(2+)-triggered Aß(1-40) fibers have been systematically studied by using turbidity essay, BCA essay, atomic force microscopy, transmission electron microscopy, and isothermal titration microcalorimetry. The results show that the binding affinity of Cu(2+) with CQ, SDUC, and EDTA is in the order of CQ > EDTA > SDUC, while the disaggregation ability to Cu(2+)-triggered Aß(1-40) fibers is in the order of CQ > SDUC > EDTA. Therefore, the disaggregation ability of chelators to the Aß(1-40) fibers does not only depend on the binding affinity of the chelators with Cu(2+). Strong self-assembly ability of SDUC and π-π interaction of the conjugate group of CQ also contributes toward the disaggregation of the Cu(2+)-triggered Aß(1-40) fibers and result in the formation of mixed small aggregates.