Emerging roles of nitric oxide in neurodegeneration.

Nitric oxide (NO) is a gaseous signaling molecule which has physiological and pathological roles in the cell. Under normal conditions, NO is produced by nitric oxide synthase (NOS) and can induce physiological responses such as vasodilation. However, over-activation of NOS has been linked to a number of human pathological conditions. For instance, most neurodegenerative disorders are marked by the presence of nitrated protein aggregates. How nitrosative stress leads to neurodegeneration is not clear, but various studies suggest that increased nitrosative stress causes protein nitration which then leads to protein aggregation. Protein aggregates are highly toxic to neurons and can promote neurodegeneration. In addition to inducing protein aggregation, recent studies show that nitrosative stress can also compromise a number of neuroprotective pathways by modifying activities of certain proteins through S-nitrosylation. These findings suggest that increased nitrosative stress can contribute to neurodegeneration through multiple pathways.