Redox Processes of Methionine Relevant to β-Amyloid Oxidation and Alzheimerʹs Disease

This minireview gives an overview over the oxidation mechanisms of methionine (Met) relevant for analogous processes which may lead to the oxidation of β-amyloid (βA) peptides. The CuII-catalyzed oxidation of a C-terminal Met35 residue in βA peptides may be a key to the known propensities of these peptides to form H2O2 and free radicals. Though the reduction potentials of CuII and Met would seem unfavorable, there are several structural features of βA, which may promote a one-electron oxidation of Met. The potentially close association of the Met sulfur with the C=O group C-terminal of Ile31 in the C-terminus of βA may support the formation of an S–O bonded radical cation intermediate. Evidence for such S–O bond formation has recently been obtained for a model, N-acetylmethionine amide. Additional support for a potential catalytic role of an oxygen-containing functional group comes from numerous studies with organic model sulfides.