Attenuated cytotoxicity but enhanced betafibril of a mutant amyloid beta-peptide with a methionine to cysteine substitution

• Published in: FEBS letters 2007-04, Vol.581 (7), p.1269
• Main Authors: Dai, Xue-Ling, Sun, Ya-Xuan, Jiang, Zhao-Feng
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amino Acid Substitution; Amyloid - chemistry; Amyloid beta-Peptides - chemical synthesis; Amyloid beta-Peptides - chemistry; Amyloid beta-Peptides - toxicity; Animals; Cells, Cultured; Circular Dichroism; Cysteine - chemistry; Humans; Methionine - chemistry; Molecular Sequence Data; Neurons - drug effects; Peptide Fragments - chemical synthesis; Peptide Fragments - chemistry; Peptide Fragments - toxicity; Protein Structure, Secondary; Rats
• ISSN: 0014-5793

Amyloid-beta peptide (Abeta), the major constituent of senile plaques in the Alzheimer's disease (AD) brain, is the main source of oxidative stress leading to neurodegeneration. The methionine residue in this peptide is reported to be responsible for neurotoxicity. Structurally similar substitution with methionine 35 replaced by cysteine in Abeta(40) was synthesized, and this result in enhanced beta-sheet structures according to both circular dichroism (CD) spectra and beta-fibril specific fluorescence assay but attenuated cytotoxicity whether in the presence of copper or not. These findings may provide further evidence on disclosing the connection between amyloid beta-aggregation and Abeta-induced neurotoxicity.