Partial Destabilization of Amyloid-β Protofibril by Methionine Photo-Oxidation: A Molecular Dynamic Simulation Study.

ABSTRACT: Selective photosensitized oxidation of amyloid protein aggregates is being investigated as a possible therapeutic strategy for treating Alzheimer's disease (AD). Photo-oxidation has been shown to degrade amyloid-β (Aβ) aggregates and ameliorate aggregate toxicity in vitro and reduce aggregate levels in the brains of AD animal models. To shed light on the mechanism by which photo-oxidation induces fibril destabilization, we carried out an all-atom molecular dynamics (MD) simulation to examine the effect of methionine (Met35) oxidation on the conformation and stability of a β-sheet-rich Aβ_9-40 protofibril. Analyses of up to 1 μs simulations showed that the oxidation of the Met35 residues, which resulted in the addition of hydrophilic oxygens in the fibril core, reduced the overall

SUBMITTER: Maghsoodi F 

PROVIDER: S-EPMC10035002 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature