Title
Aluminum-triggered structural modifications and aggregation of β-amyloids
Author
F. Ricchelli, D. Drago, B. Filippi, G. Tognon, P. Zatta
Year
2005
Journal
Cellular and Molecular Life Sciences
Abstract
We investigated the structural effects induced by Al3+ on different b-amyloid (Ab) 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 b 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+-Ab(1–42) complex. Comparative studies showed that Zn2+ and Cu2+ were much less efficient than Al3+ in stimuCMLS, Cell. Mol. Life Sci. 62 (2005) 1724–1733 1420-682X/05/151724-10 DOI 10.1007/s00018-005-5141-0 © Birkhäuser Verlag, Basel, 2005 CMLS Cellular and Molecular Life Sciences lating the spontaneous aggregation/fibrillogenesis of Abs. Studies with liposomes as membrane models showed dramatic changes in the structural properties of the lipid bilayer in the presence of Al3+-Ab complexes, suggesting a major role of Al3+ in Ab-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 Ab aggregation in the extracellular spaces.
Instrument
J-715
Keywords
Circular dichroism, Secondary structure, Ligand binding, Biochemistry