S-Nitrosylation Regulates Cell Survival and Death in the Central Nervous System

Nitric oxide (NO), which is produced from nitric oxide synthase, is an important cell signaling molecule that is crucial for many physiological functions such as neuronal death, neuronal survival, synaptic plasticity, and vascular homeostasis. This diffusible gaseous compound functions as an effector or second messenger in many intercellular communications and/or cell signaling pathways. Protein S-nitrosylation is a posttranslational modification that involves the covalent attachment of an NO group to the thiol side chain of select cysteine residues on target proteins. This process is thought to be very important for the regulation of cell death, cell survival, and gene expression in the central nervous system (CNS). However, there have been few reports on the role of protein S-nitrosylation in CNS disorders. Here, we briefly review specific examples of S-nitrosylation, with particular emphasis on its functions in neuronal cell death and survival. An understanding of the role and mechanisms underlying the effects of protein S-nitrosylation on neurodegenerative/neuroprotective events may reveal a novel therapeutic strategy for rescuing neurons in neurodegenerative diseases.