期刊
CELLULAR AND MOLECULAR LIFE SCIENCES
卷 62, 期 15, 页码 1724-1733出版社
SPRINGER BASEL AG
DOI: 10.1007/s00018-005-5141-0
关键词
Alzheimer; metal ions; aluminum; amyloid; copper; zinc
We investigated the structural effects induced by Al3+ on different beta-amyloid (A beta) 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+-A beta((1-42)) complex. Comparative studies showed that Zn2+ and Cu2+ were much less efficient than Al3+ in stimulating the spontaneous aggregation/fibrillogenesis of A beta s. Studies with liposomes as membrane models showed dramatic changes in the structural properties of the lipid bilayer in the presence of Al3+-A beta complexes, suggesting a major role of Al3+ in A beta-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 A beta aggregation in the extracellular spaces.
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