title: Aberrant protein s-nitrosylation in neurodegenerative diseases.
abstract: S-Nitrosylation is a redox-mediated posttranslational modification that regulates protein function via covalent reaction of nitric oxide (NO)-related species with a cysteine thiol group on the target protein. Under physiological conditions, S-nitrosylation can be an important modulator of signal transduction pathways, akin to phosphorylation. However, with aging or environmental toxins that generate excessive NO, aberrant S-nitrosylation reactions can occur and affect protein misfolding, mitochondrial fragmentation, synaptic function, apoptosis or autophagy. Here, we discuss how aberrantly S-nitrosylated proteins (SNO-proteins) play a crucial role in the pathogenesis of neurodegenerative diseases, including Alzheimer's and Parkinson's diseases. Insight into the pathophysiological role of aberrant S-nitrosylation pathways will enhance our understanding of molecular mechanisms leading to neurodegenerative diseases and point to potential therapeutic interventions.
authors.affiliation: Del E. Web Center for Neuroscience, Aging, and Stem Cell Research, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA. tnakamura@sanfordburnham.org
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nakamura
authors.forename: Shichun
authors.initials: S
authors.lastname: Tu
authors.forename: Mohd Waseem
authors.initials: MW
authors.lastname: Akhtar
authors.forename: Carmen R
authors.initials: CR
authors.lastname: Sunico
authors.forename: Shu-Ichi
authors.initials: S
authors.lastname: Okamoto
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Lipton
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D026361:Reactive Nitrogen Species / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; D026361:Reactive Nitrogen Species; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase