Nitric oxide signaling and nitrosative stress in neurons: role for S-nitrosylation

Nitric oxide (NO) mediates cellular signaling pathways that regulate a plethora of physiological processes. One of the signaling mechanisms mediated by NO is through S-nitrosylation of cysteine residues in target proteins, which is now regarded as an important redox-based physiological action. Deregulation of the protein S-nitrosylation upon nitrosative stress, however, has also been linked to various human diseases, such as neurodegenerative disorders. Between these physiological and pathophysiological roles, there are mechanisms whereby a milder level of nitrosative stress provides S-nitrosylation of some proteins that counteracts the pathological processes, serving as a negative feedback mechanism. In addition, NO has recently emerged as a mediator of epigenetic gene expression and chromatin changes. In this review, these molecular mechanisms, especially those in the central nervous system and neurodegenerative disorders, are described.