title: Protein S-Nitrosylation as a Therapeutic Target for Neurodegenerative Diseases.
abstract: 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.
authors.affiliation: Scintillon Institute, San Diego, CA 92121, USA. Electronic address: tnakamura@scintillon.org.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Scintillon Institute, San Diego, CA 92121, USA; Department of Neurosciences, University of California, San Diego School of Medicine, La Jolla, CA 92039, USA. Electronic address: slipton@ucsd.edu.
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Lipton
mesh_terms: D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006801:Humans; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D015538:Nitrosation; D011499:Protein Processing, Post-Translational; D026361:Reactive Nitrogen Species / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D026403:S-Nitrosothiols / Q000378:metabolism; D015290:Second Messenger Systems
chemical_list: D026361:Reactive Nitrogen Species; D016194:Receptors, N-Methyl-D-Aspartate; D026403:S-Nitrosothiols; D009569:Nitric Oxide; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases
keywords: Alzheimer's disease; NitroMemantine; Parkinson's disease; denitrosylation; protein S-nitrosylation; transnitrosylation