Abeta-mediated ROS production by Cu ions: structural insights, mechanisms and relevance to Alzheimer's disease

Abstract

Metal ions are involved in Alzheimer's disease (AD) via their ability to induce aggregation of amyloidogenic peptide and production of Reactive Oxygen Species (ROS), two key events in the development of the pathology. Here, we review very recent results concerning the coordination of Cu(I) and Cu(II) ion to the amyloid-beta peptide, the one encountered in AD. Implications of these structural data for the redox chemistry of the Cu(I/II)-Abeta couple are discussed. The different pathways for the ROS generation by the Cu(I/II)-Abeta species are described. In the more relevant one, reduction of dioxygen is realized by a two-electron process involving two Cu(I) in close vicinity, while the production of the hydroxyl radical from hydrogen peroxide is less constrained. A brief summary of how the Abeta peptide is oxidised during the ROS production is also given. Lastly, the pro- vs. anti-oxidant properties of Abeta are commented on.