Aluminum-triggered structural modifications and aggregation of beta-amyloids.
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.
CNR Institute of Biomedical Technologies, Metalloproteins Unit, Department of Biology, University of Padova, Viale G. Colombo, 3-35121, Padova, Italy.
F
F
Ricchelli
D
D
Drago
B
B
Filippi
G
G
Tognon
P
P
Zatta
D000535:Aluminum / Q000494:pharmacology*; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000648:ultrastructure; D052160:Benzothiazoles; D002614:Chelating Agents / Q000494:pharmacology; D002942:Circular Dichroism; D003676:Deferoxamine / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D008081:Liposomes; D010446:Peptide Fragments / Q000737:chemistry; D011487:Protein Conformation / Q000187:drug effects; D013050:Spectrometry, Fluorescence; D013844:Thiazoles / Q000737:chemistry
D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D002614:Chelating Agents; D005456:Fluorescent Dyes; D008081:Liposomes; D010446:Peptide Fragments; D013844:Thiazoles; C009462:thioflavin T; D000535:Aluminum; D003676:Deferoxamine