Chemical and mechanistic analysis of photodynamic inhibition of Alzheimer's beta-amyloid aggregation

Abstract

The self-assembly of the beta-amyloid peptide (A) into amyloid aggregates is a central phenomenon associated with Alzheimer's disease. Here, we report chemical modifications of key amino acid residues of A(42) (Y10, H13, H14, and M35) by photoexcited thioflavin-T (ThT), a fluorescent probe of amyloid structure. The quantitative chemical kinetics analysis shows that the oxidized monomer species does not self-assemble, nor perturb the aggregation kinetics of non-oxidized A beta(42).