| | Attenuated cytotoxicity but enhanced βfibril of a mutant amyloid β-peptide with a methionine to cysteine substitutionEdited by Gianni Cesareni Received 6 February 2007; received in revised form 14 February 2007; accepted 14 February 2007. published online 01 March 2007. Abstract Amyloid-β peptide (Aβ), 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 Aβ40 was synthesized, and this result in enhanced β-sheet structures according to both circular dichroism (CD) spectra and β-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 β-aggregation and Aβ-induced neurotoxicity. Abbreviations: AD, Alzheimer’s disease, Aβ, amyloid-β peptide, APP, amyloid precursor protein, ROS, reactive oxygen species, CD, circular dichroism, HFIP, 1,1,1,3,3,3-hexafluoro-2-propanol, WT, wide type, ThT, thioflavin T, OD, optical density, MTT, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide, DMSO, dimethyl sulfoxide a College of Life Science, Capital Normal University, Beijing 100037, China b College of Applied Sciences and Humanities of Beijing Union University, Beijing 100083, China  Corresponding author. Fax: +86 10 64900143.
PII: S0014-5793(07)00204-9 doi:10.1016/j.febslet.2007.02.038 © 2007 Federation of European Biochemical Societies | |
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ABSTRACT
