NO synthase and NO-dependent signal pathways in brain aging and neurodegenerative disorders: The role of oxidant/antioxidant balance

Nitric oxide and other reactive nitrogen species appear to play several cru cial roles in the brain. These include physiological processes such as neur omodulation, neurotransmission and synaptic plasticity, and pathological pr ocesses such as neurodegeneration and neuroinflammation. There is increasin g evidence that glial cells in the central nervous system can produce nitri c oxide in vivo in response to stimulation by cytokines and that this produ ction is mediated by the inducible isoform of nitric oxide synthase. Althou gh the etiology and pathogenesis of the major neurodegenerative and neuroin flammatory disorders (Alzheimer's disease, amyothrophic lateral sclerosis, Parkinson's disease, Huntington's disease and multiple sclerosis) are unkno wn, numerous recent studies strongly suggest that reactive nitrogen species play an important role. Furthermore, these species are probably involved i n brain damage following ischemia and reperfusion, Down's syndrome and mito chondrial encephalopathies. Recent evidence also indicates the importance o f cytoprotective proteins such as heat shock proteins (HSPs) which appear t o be critically involved in protection from nitrosative and oxidative stres s. In this review, evidence for the involvement of nitrosative stress in th e pathogenesis of the major neurodegenerative/neuroinflammatory diseases an d the mechanisms operating in brain as a response to imbalance in the oxida nt/antioxidant status are discussed.