ABSTRACT
As in other cell types, the principal reactive oxygen species (ROS) generated in neurons is superoxide anion radical (O2 *) which arises from the electron transport process in mitochondria (Fig. 1). Neurons express two different superoxide dismutases (Mn-SOD, which is localized in mitochondria, and Cu/Zn-SOD, which is located primarily in the cytoplasm) which convert O2 * to hydrogen peroxide (H20 2). The brain contains high levels of iron which, when in the Fe2+ form, catalyzes the conversion of H20 2 to the highly destructive hydroxyl radical (OH*). Hydroxyl radical is a potent inducer of membrane lipid peroxidation, an autocatalytic process involving propagation of an initial free radical attack on double bonds of polyunsaturated membrane fatty acids. When membrane lipids are peroxidized a toxic aldehyde called 4-hydroxynonenal is liberated which can cova lently modify proteins (on cysteine, lysine, and histidine residues) and thereby impair their function (1,2). Protein targets of 4-hydroxynonenal that appear to play a role in its neurotoxic actions are membrane ion-motive ATPases (3,4), glucose transporters (5,6), and glutamate transporters (6,7). Another oxy radical pathway that appears to be a major contributor to neurodegenerative processes involves the interaction of O2 * with nitric oxide (NO) resulting in the formation
Figure 1 Mechanisms for production and removal of reactive oxygen species in neurons, and mechanisms responsible for oxidative stress-induced disruption of neuronal ion homeostasis. See text for discussion.
