title: Metal-catalyzed oxidation of Aβ and the resulting reorganization of Cu binding sites promote ROS production.
abstract: In the context of Alzheimer's disease (AD), the production of HO˙ by copper-amyloid beta (Aβ) in the presence of ascorbate is known to be deleterious for the Aβ peptide itself and also for the surrounding molecules, thus establishing a direct link between AD and oxidative stress. The metal-catalyzed oxidation (MCO) of Aβ primarily targets the residues involved in copper coordination during HO˙ production. In the present work, we demonstrate that the oxidative damage undergone by Aβ during MCO lead to a change in copper coordination, with enhanced catalytic properties that increases the rates of ascorbate consumption and HO˙ production, and the amount of HO˙ released by the system. This phenomenon is observed after the peptide has been sufficiently oxidized.
authors.affiliation: LCC (Laboratoire de Chimie de Coordination), CNRS UPR 8241, 205 route de Narbonne, 31062 Toulouse Cedex 09, France. clemence.cheignon@lcc-toulouse.fr fabrice.collin@univ-tlse3.fr and Université de Toulouse, UPS, INPT, 31077 Toulouse, France and UMR 152 Pharma Dev, Université de Toulouse, IRD, UPS, France.
authors.forename: Clémence
authors.initials: C
authors.lastname: Cheignon
authors.affiliation: LCC (Laboratoire de Chimie de Coordination), CNRS UPR 8241, 205 route de Narbonne, 31062 Toulouse Cedex 09, France. clemence.cheignon@lcc-toulouse.fr fabrice.collin@univ-tlse3.fr and Université de Toulouse, UPS, INPT, 31077 Toulouse, France.
authors.forename: Peter
authors.initials: P
authors.lastname: Faller
authors.affiliation: University of Grenoble Alpes, Institut NEEL, F-38000 Grenoble, France and CNRS, Institut NEEL, F-38000 Grenoble, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Testemale
authors.affiliation: LCC (Laboratoire de Chimie de Coordination), CNRS UPR 8241, 205 route de Narbonne, 31062 Toulouse Cedex 09, France. clemence.cheignon@lcc-toulouse.fr fabrice.collin@univ-tlse3.fr and Université de Toulouse, UPS, INPT, 31077 Toulouse, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Hureau
authors.affiliation: LCC (Laboratoire de Chimie de Coordination), CNRS UPR 8241, 205 route de Narbonne, 31062 Toulouse Cedex 09, France. clemence.cheignon@lcc-toulouse.fr fabrice.collin@univ-tlse3.fr and Université de Toulouse, UPS, INPT, 31077 Toulouse, France and UMR 152 Pharma Dev, Université de Toulouse, IRD, UPS, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Collin
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D001205:Ascorbic Acid / Q000378:metabolism; D001665:Binding Sites; D003300:Copper / Q000378:metabolism*; D006801:Humans; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D017382:Reactive Oxygen Species; D003300:Copper; D001205:Ascorbic Acid