Aluminum-triggered structural modifications and aggregation of β-amyloids

Abstract.

We investigated the structural effects induced by Al³⁺ on different β-amyloid (Aβ) fragments at pH 7.4 and T= 25°C, with particular attention given to the sequences 1–40 and 1–42. Al³⁺ caused peptide enrichment in β sheet structure and formation of solvent-exposed hydrophobic clusters. These intermediates evolved to polymeric aggregates which organized in fibrillar forms in the case of the Al³⁺-Aβ_(1–42) complex. Comparative studies showed that Zn²⁺ and Cu²⁺ were much less efficient than Al³⁺ in stimulating the spontaneous aggregation/fibrillogenesis of Aβs. Studies with liposomes as membrane models showed dramatic changes in the structural properties of the lipid bilayer in the presence of Al³⁺-Aβ complexes, suggesting a major role of Al³⁺ in Aβ-induced cell dysfunction. Al³⁺ effects were abolished by desferrioxamine mesylate (DFO) only in solution. We concluded that, in vivo, DFO may act as a protective agent by preventing or reverting Aβ aggregation in the extracellular spaces.