title: 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.
authors.affiliation: Laboratoire d'Electrochimie, Chimie des Interfaces et Modélisation pour l'Energie, CNRS UMR-7575, Ecole Nationale Supérieure de Chimie de Paris - Chimie-ParisTech, 11 rue P. et M. Curie, F-75231 Paris Cedex 05, France.
authors.forename: Roberto
authors.initials: R
authors.lastname: Giacovazzi
authors.forename: Ilaria
authors.initials: I
authors.lastname: Ciofini
authors.forename: Li
authors.initials: L
authors.lastname: Rao
authors.forename: Christian
authors.initials: C
authors.lastname: Amatore
authors.forename: Carlo
authors.initials: C
authors.lastname: Adamo
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry*; D001921:Brain / Q000378:metabolism*; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D008958:Models, Molecular; D030421:Peroxynitrous Acid / Q000096:biosynthesis*
chemical_list: D016229:Amyloid beta-Peptides; D030421:Peroxynitrous Acid; D003300:Copper