Protein Aging and Its Relevance to the Etiology of Alzheimer’s Disease

Abstract

The oxidative modification of proteins is elicited by a number of reactive oxygen species (ROS) that are produced endogenously as minor by-products of normal electron transport processes in metabolism, by exposure to oxidative stress as a consequence of metabolic disorders or environmental challenges, and by metal-catalyzed oxidation (MCO) systems. The ROS most commonly implicated in protein modification are hydroxyl radical (OH•), superoxide anion radical (O2 •−), nitric oxide radical (NO•), thiyl radical (RS•), perferryl radical (FeO2 2+), ferryl radical (FeO2+), and various non-radical species, such as hydrogen peroxide (H2O2), ozone (O3), singlet oxygen (1O2), peroxynitrite (HONOO), nitronium ion (NO2 +), and hypochlorous acid (HOC1). Whereas each of these ROS may contribute to biological damage under a particular set of conditions, it is generally accepted that OH• is the most damaging ROS under most physiological conditions. Hydroxyl radicals are readily generated by at least four different mechanisms: (a) the homolytic cleavage of water by ionizing radiation (X-rays, gamma rays), reaction (1), which describes the overall reaction in which aqueous electrons (eaq −) , H2O+, and an excited state of water (H2O*) are intermediates (Swallow 1960); (b) cleavage of H2O2 by reaction with either Fe(II) or Cu(I), the Fenton reaction, reaction (2); (c) by homolytic cleavage of peroxynitrite, reaction (3) (Beckman et al. 1990); (d) by reaction of ozone with a phenol (PH), reaction (4) (Grimes et al. 1988; Pryor 1994).