Aluminum-triggered structural modifications and aggregation of beta-amyloids

• Published in: Cellular and molecular life sciences : CMLS Vol. 62; no. 15; pp. 1724 - 1733
• Main Authors: Ricchelli, F, Drago, D, Filippi, B, Tognon, G, Zatta, P
• Format: Journal Article
• Language: English
• Published: Switzerland Birkhäuser-Verlag 01.08.2005
• Subjects: Aluminum - pharmacology; Amyloid beta-Peptides - chemistry; Amyloid beta-Peptides - ultrastructure; Benzothiazoles; Chelating Agents - pharmacology; Circular Dichroism; Deferoxamine - pharmacology; Fluorescent Dyes - chemistry; Hydrophobic and Hydrophilic Interactions; Liposomes; Peptide Fragments - chemistry; Protein Conformation - drug effects; Spectrometry, Fluorescence; Thiazoles - chemistry
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s00018-005-5141-0

We investigated the structural effects induced by Al3+ on different beta-amyloid (Abeta) fragments at pH 7.4 and T=25 degrees C, with particular attention given to the sequences 1-40 and 1-42. Al3+ caused peptide enrichment in beta 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+-Abeta(1-42) complex. Comparative studies showed that Zn2+ and Cu2+ were much less efficient than Al3+ in stimulating the spontaneous aggregation/fibrillogenesis of Abetas. Studies with liposomes as membrane models showed dramatic changes in the structural properties of the lipid bilayer in the presence of Al3+-Abeta complexes, suggesting a major role of Al3+ in Abeta-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 Abeta aggregation in the extracellular spaces.