Aluminum-triggered structural modifications and aggregation of β-amyloids
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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.
Key words.Alzheimer metal ions aluminum amyloid copper zinc
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