Advertisement

Cellular and Molecular Life Sciences CMLS

, Volume 62, Issue 15, pp 1724–1733 | Cite as

Aluminum-triggered structural modifications and aggregation of β-amyloids

  • F. Ricchelli
  • D. Drago
  • B. Filippi
  • G. Tognon
  • P. ZattaEmail author
Research Article

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.

Key words.

Alzheimer metal ions aluminum amyloid copper zinc 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Copyright information

© Birkhäuser Verlag, Basel 2005

Authors and Affiliations

  • F. Ricchelli
    • 1
  • D. Drago
    • 1
  • B. Filippi
    • 2
  • G. Tognon
    • 1
  • P. Zatta
    • 1
    Email author
  1. 1.CNR Institute of Biomedical Technologies, Metalloproteins Unit, Department of BiologyUniversity of PadovaPadovaItaly
  2. 2.Department of Chemical SciencesUniversity of PadovaPadovaItaly

Personalised recommendations