Evidence of cadmium and mercury involvement in the Aβ42 aggregation process

Abstract

Aβ42 is a small peptide formed from 42 aminoacids that presents a great propensity to aggregate until it forms fibrils. Aβ42 aggregation and fibrillation are very complex processes whose molecular mechanisms seem to depend on characteristics intrinsic to the peptide molecule, as well as extrinsic factors. Peptide concentration, mean pH and several substances, including metal ions, are principal extrinsic factors for the oligomerization process. Different metals affect the aggregation of the Aβ42 molecule, and their toxicity favours the misfolding and aggregation of the peptide. In this study, we evaluate the effect of different concentrations of Cd²⁺ and Hg²⁺ on the Aβ42 peptide in solution by different methods. The toxicity of Aβ42 was evaluated with the MTT assay, while the aggregation process was monitored by single-channel measurements, electrophoresis and western blot. Cd²⁺ and Hg²⁺ seem to favour the formation of high-molecular-weight aggregates, to decrease ion channel turnover inside the membrane and to significantly increase Aβ42 toxicity.

Keywords: Aggregation; Aβ42; Cadmium; Cytotoxicity; Mercury.