Methionine oxidation: Implications for the mechanism of toxicity of the β-amyloid peptide from Alzheimer's disease

Abstract

The amyloid β-peptide, Aβ is toxic to neurons and this toxicity plays a central role in the progression of Alzheimer's disease. The mechanism(s) by which Aβ exerts its toxicity has been hotly debated with several theories postulated. Here we discuss the role of oxidation of the sulfur atom of Met35 in Aβ42 (Met(O)Aβ), a modification that has significant implications for the mechanism of Aβ toxicity. Both Met(O)Aβ and its native form display toxicity to primary neuronal cells in culture which can be rescued by catalase, a H2O2 inhibitor and clioquinol a mild copper chelator. However both native Aβ and Met(O)Aβ differ substantially in primary and secondary structures, solubility, ability to pe..