Aluminum-triggered structural modifications and aggregation of beta-amyloids.
Cell Mol Life Sci
; 62(15): 1724-33, 2005 Aug.
Article
in En
| MEDLINE
| ID: mdl-15990957
ABSTRACT
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Amyloid beta-Peptides
/
Aluminum
Language:
En
Journal:
Cell Mol Life Sci
Year:
2005
Document type:
Article