Aggregated β-amyloid peptides (Aβ) are neurotoxic and responsible for neuronal death both in vitro and in vivo. From the structural point of view, Aβ self-aggregation involves a conformational change in the peptide. Here, we investigated the relationship between conformational changes and amino acid residues of Aβ40. Urea unfolding in combination with NMR spectroscopy was applied to probe the stabilization of Aβ40 conformation. L17 and F19 residues were found more sensitive to environmental changes than the other residues. Replacement of these two residues with alanine could stabilize the conformation of Aβ40. Further analysis indicated that the Aβ40(L17A/F19A) mutant could diminish the aggregation and reduce the neurotoxicity. These results suggest that L17 and F19 are the critical residues responsible for conformational changes which may trigger neurotoxic cascade of Aβ40.
|頁（從 - 到）||91-95|
|期刊||Biochemical and Biophysical Research Communications|
|出版狀態||Published - 4 2月 2011|