Nitric Oxide and Oxidative Damage in the CNS
NO is synthesized by a family of enzymes known collectively as NO synthases that catalyze the reaction of L-arginine with molecular oxygen to form NO and L-citrulline. The NO synthases can be divided into 2 main groups: a) constitutive isoforms that are continuously expressed and b) inducible isoforms, the de novo synthesis of which is stimulated by cytokines or bacterial-derived lipopolysaccharide (LPS) acting alone or in synergy (Nathan, 1992; Moncada et al., 1991). Although all NO synthases catalyze the same basic reaction, they are structurally and, to a certain extent, functionally distinct enzymes encoded by separate genes (Nathan, 1992). Several important differences exist between constitutive and inducible NO synthases in terms of requirement of Ca2+ for enzyme activation, cellular localization, and perhaps most importantly in the context of this chapter, the actual amount of NO generated. These differences, discussed below, have considerable implications for both NO-dependent toxicity and the development of NO synthase inhibitors as efficacious cytoprotective drugs.
KeywordsMultiple Sclerosis Nitric Oxide Experimental Autoimmune Encephalomyelitis Multiple System Atrophy Multiple Sclerosis Lesion
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