title: Nitric Oxide-Mediated Posttranslational Modifications: Impacts at the Synapse.
abstract: Nitric oxide (NO) is an important gasotransmitter molecule that is involved in numerous physiological processes throughout the nervous system. In addition to its involvement in physiological plasticity processes (long-term potentiation, LTP; long-term depression, LTD) which can include NMDAR-mediated calcium-dependent activation of neuronal nitric oxide synthase (nNOS), new insights into physiological and pathological consequences of nitrergic signalling have recently emerged. In addition to the canonical cGMP-mediated signalling, NO is also implicated in numerous pathways involving posttranslational modifications. In this review we discuss the multiple effects of S-nitrosylation and 3-nitrotyrosination on proteins with potential modulation of function but limit the analyses to signalling involved in synaptic transmission and vesicular release. Here, crucial proteins which mediate synaptic transmission can undergo posttranslational modifications with either pre- or postsynaptic origin. During normal brain function, both pathways serve as important cellular signalling cascades that modulate a diverse array of physiological processes, including synaptic plasticity, transcriptional activity, and neuronal survival. In contrast, evidence suggests that aging and disease can induce nitrosative stress via excessive NO production. Consequently, uncontrolled S-nitrosylation/3-nitrotyrosination can occur and represent pathological features that contribute to the onset and progression of various neurodegenerative diseases, including Parkinson's, Alzheimer's, and Huntington's.
authors.affiliation: MRC Toxicology Unit, Hodgkin Building, Leicester LE1 9HN, UK.
authors.forename: Sophie A
authors.initials: SA
authors.lastname: Bradley
authors.affiliation: MRC Toxicology Unit, Hodgkin Building, Leicester LE1 9HN, UK.
authors.forename: Joern R
authors.initials: JR
authors.lastname: Steinert
mesh_terms: D000818:Animals; D006801:Humans; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D013569:Synapses / Q000378:metabolism* / Q000473:pathology; D009435:Synaptic Transmission
chemical_list: D009569:Nitric Oxide; C496320:NOS1 protein, human; D052248:Nitric Oxide Synthase Type I