Aluminum-triggered structural modifications and aggregation of β-amyloids

F. Ricchelli, D. Drago, B. Filippi, G. Tognon, P. Zatta

Research output: Contribution to journalArticlepeer-review

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 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.

Original languageEnglish
Pages (from-to)1724-1733
Number of pages10
JournalCellular and Molecular Life Sciences
Volume62
Issue number15
DOIs
Publication statusPublished - Aug 2005

Keywords

  • Aluminum
  • Alzheimer
  • Amyloid
  • Copper
  • Metal ions
  • Zinc

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Cell Biology

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