Protein S-nitrosylation: role for nitric oxide signaling in neuronal death

Abstract Background One of the signaling mechanisms mediated by nitric oxide (NO) is through S -nitrosylation, the reversible redox-based modification of cysteine residues, on target proteins that regulate a myriad of physiological and pathophysiological processes. In particular, an increasing number of studies have identified important roles for S -nitrosylation in regulating cell death. Scope of review The present review focuses on different targets and functional consequences associated with nitric oxide and protein S-nitrosylation during neuronal cell death. Major conclusions S -Nitrosylation exhibits double-edged effects dependent on the levels, spatiotemporal distribution, and origins of NO in the brain: in general Snitrosylation resulting from the basal low level of NO in cells exerts anti-cell death effects, whereas S -nitrosylation elicited by induced NO upon stressed conditions is implicated in pro-cell death effects. General Significance Dysregulated protein S -nitrosylation is implicated in the pathogenesis of several diseases including degenerative diseases of the central nervous system (CNS). Elucidating specific targets of S -nitrosylation as well as their regulatory mechanisms may aid in the development of therapeutic intervention in a wide range of brain diseases.