Copper–amyloid-β complex may catalyze peroxynitrite production in brain: evidence from molecular modeling
Literature Information
Ilaria Ciofini, Li Rao, Christian Amatore
Rationalization of the origin of peroxynitrite-related damages in the brain of Alzheimer's disease (AD) patients linking to functional hyperemia, inexplicable on the basis of the accepted hydrogen peroxide catalytic route, is here provided by molecular modeling. The present theoretical work indeed strongly supports the facile occurrence of an Aβ-catalyzed generation of peroxynitrite in the brain, alternative to the already accepted H2O2-route, whenever ascorbate, dioxygen and nitric oxide are present near Cu–Aβ complexes without the necessity of generating short-lived superoxide ions. The proposed route requires nitric oxide and dioxygen to be simultaneously present at sufficiently high concentrations near Cu–Aβ complexes, requirement which is frequently fulfilled in brain during functional hyperemia. Conversely, hydrogen peroxide would be produced during resting phases.
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