Effects of clioquinol on metal-triggered amyloid-beta aggregation revisited.

ABSTRACT

Amyloid-beta (Abeta) plaques are largely associated with the neuropathogenesis of Alzheimer's disease (AD). Metal ions such as Cu(II) and Zn(II) have been implicated as contributors to their formation and deposition. Metal chelators have been used to modulate metal-induced Abeta aggregation. The bidentate ligand clioquinol (CQ) presents an effective influence on metal-involved Abeta aggregation, which has been explained through its metal chelation and is generally monitored by fluorescence and turbidity assays in vitro. The studies herein, however, suggest that the effects of CQ on metal-driven Abeta aggregation may not be visualized accurately by both assays. Subsequently, the present work demonstrates that CQ is able to chelate metal ions from metal-Abeta species and to assist, in part, in the disaggregation of Abeta aggregates, but it could not completely hinder the progression of Abeta aggregation.