Protein S-Nitrosylation as a Therapeutic Target for Neurodegenerative Diseases

At physiological levels, nitric oxide (NO) contributes to the maintenance of normal neuronal activity and survival, thus serving as an important regulatory mechanism in the central nervous system. By contrast, accumulating evidence suggests that exposure to environmental toxins or the normal aging process can trigger excessive production of reactive oxygen/nitrogen species (such as NO), contributing to the etiology of several neurodegenerative diseases. We highlight here protein S-nitrosylation, resulting from covalent attachment of an NO group to a cysteine thiol of the target protein, as a ubiquitous effector of NO signaling in both health and disease. We review our current understanding of this redox-dependent post-translational modification under neurodegenerative conditions, and evaluate how targeting dysregulated protein S-nitrosylation can lead to novel therapeutics.

TrendsProtein S-nitrosylation represents an important component of NO signaling.S-Nitrosylation mediates both physiological and pathological brain signaling.NitroMemantine protects neurons via S-nitrosylation of NMDA receptors.CGP3466B (or TCH346) is neuroprotective by inhibiting formation of SNO-GAPDH.