Issue 21, 2014

Copper–amyloid-β complex may catalyze peroxynitrite production in brain: evidence from molecular modeling

Abstract

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.

Graphical abstract: Copper–amyloid-β complex may catalyze peroxynitrite production in brain: evidence from molecular modeling

Supplementary files

Article information

Article type
Paper
Submitted
15 نومبر 2013
Accepted
10 جنؤری 2014
First published
15 جنؤری 2014

Phys. Chem. Chem. Phys., 2014,16, 10169-10174

Author version available

Copper–amyloid-β complex may catalyze peroxynitrite production in brain: evidence from molecular modeling

R. Giacovazzi, I. Ciofini, L. Rao, C. Amatore and C. Adamo, Phys. Chem. Chem. Phys., 2014, 16, 10169 DOI: 10.1039/C3CP54839B

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