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

Clémence Cheignon (1, 2) , Peter Faller (1) , Denis Testemale (3) , Christelle Hureau (1) , Fabrice Collin (1, 2)

1 LCC - Laboratoire de chimie de coordination
2 PHARMA-DEV - Pharmacochimie et Biologie pour le Développement
3 NEEL - MRS - Matériaux, Rayonnements, Structure

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.

Mots clés: AMYLOID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; HYDROGEN-PEROXIDE; COPPER-BINDING; HYDROXYL RADICALS; MASS-SPECTROMETRY; PHYSIOLOGICAL PH; PEPTIDE; COORDINATION; COMPLEXES

Domaines: Chimie de coordination; Neurobiologie

Clémence Cheignon, Peter Faller, Denis Testemale, Christelle Hureau, Fabrice Collin. Metal-catalyzed oxidation of Aβ and the resulting reorganization of Cu binding sites promote ROS production. Metallomics, 2016, 8 (10), pp.1081-1089. ⟨10.1039/C6MT00150E⟩. ⟨hal-01392682⟩