Metal-catalyzed oxidation of Aβ and the resulting reorganization of Cu binding sites promote ROS production. Issue 10 (1st September 2016)

• Record Type: Journal Article
• Authors: Cheignon, Clémence; Faller, Peter; Testemale, Denis; Hureau, Christelle; Collin, Fabrice
• Is Part Of: Metallomics. Volume 8:Issue 10(2016:Oct.)
• Page Start: 1081
• Page End: 1089
• Publication Date: 2016-09-01
• Subjects: Metals -- Physiological effect -- Periodicals; 572.51
• DOI: 10.1039/c6mt00150e
• Languages: English
• ISSNs: 1756-5901

Abstract

Abstract : Aβ oxidation due to HO˙ production by Cu–Aβ/ascorbate changes copper coordination and leads to the self-enhancement of HO˙ production and release. 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.