title: Attenuated cytotoxicity but enhanced betafibril of a mutant amyloid beta-peptide with a methionine to cysteine substitution.
abstract: 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.
authors.affiliation: College of Life Science, Capital Normal University, Beijing 100037, China.
authors.forename: Xue-Ling
authors.initials: XL
authors.lastname: Dai
authors.forename: Ya-Xuan
authors.initials: YX
authors.lastname: Sun
authors.forename: Zhao-Feng
authors.initials: ZF
authors.lastname: Jiang
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000682:Amyloid / Q000737:chemistry*; D016229:Amyloid beta-Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity*; D000818:Animals; D002478:Cells, Cultured; D002942:Circular Dichroism; D003545:Cysteine / Q000737:chemistry; D006801:Humans; D008715:Methionine / Q000737:chemistry; D008969:Molecular Sequence Data; D009474:Neurons / Q000187:drug effects*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity*; D017433:Protein Structure, Secondary; D051381:Rats
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D008715:Methionine; D003545:Cysteine