Metal-catalyzed oxidation of Aβ and the resulting reorganization of Cu binding sites promote ROS production

In the context of Alzheimer's disease (AD), the production of HO center dot by copper-amyloid beta (Ab) in the presence of ascorbate is known to be deleterious for the A beta peptide itself and also for the surrounding molecules, thus establishing a direct link between AD and oxidative stress. The metal-catalyzed oxidation (MCO) of A beta primarily targets the residues involved in copper coordination during HO center dot production. In the present work, we demonstrate that the oxidative damage undergone by A beta during MCO lead to a change in copper coordination, with enhanced catalytic properties that increases the rates of ascorbate consumption and HO center dot production, and the amount of HO center dot released by the system. This phenomenon is observed after the peptide has been sufficiently oxidized.