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 Al 3+-Aβ(1-42) complex. Comparative studies showed that Zn2+ and Cu2+ were much less efficient than Al 3+ 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 Al 3+-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.
- Metal ions
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Cell Biology