Abstract
S-nitrosylation is a biologically relevant post-translational protein modification with signaling consequence. In eukaryotes, a large number of proteins have been identified as S-nitrosylation targets. Derangement in protein S-nitrosylation has been implicated in the pathogenesis of a number of different disease entities including Multiple Sclerosis (MS). A growing body of evidence has shown that Nitric oxide (NO) plays a critical role in MS. NO and other reactive nitrogen species (RNS) are involved in neuroinflammation and neurodegeneration in MS. Signaling by RNS is carried out mainly by S-nitrosylation of critical cysteine residues in targeted proteins. In recent years, newer roles in MS have been attributed to RNS. These roles relate to S-nitrosylation of cysteines in proteins which has emerged as a potential new paradigm in signal transduction and regulation of protein function. In the present review we discuss the evidence for the diverse roles of S-nitrosylation in MS, including nitrosative stress-induced gene expression in MS, and S-nitrosylation of transcription factors in MS. In addition, S-nitrosylation can be therapeutically used in MS. Recent studies providing evidence for SNO-based therapy strategy in the treatment of MS will also be discussed. Undoubtedly, new exciting results will contribute to the expanding area of MS research.
Highlights
Nitric Oxide (NO) has long been recognized as a modulator of gene expression both in prokaryotic and eukaryotic cells and is an import molecule involved in many physiological and pathological processes [1,2]
Jaffrey et al found that the retinoblastoma (Rb), heat-shock protein 72 (Hsp72), isoforms 2 of the collapsin-response-mediator protein (CRMP2), and calbindin were S-nitrosylated when rat cerebellum homogenates were incubated with the NO donors GSNO [18]
These findings indicate that, some proteins are susceptible to S-nitrosylation in vitro with various NO donors, they may not be modified in vivo to any appreciable extent even under severe nitrosative stress conditions
Summary
Nitric Oxide (NO) has long been recognized as a modulator of gene expression both in prokaryotic and eukaryotic cells and is an import molecule involved in many physiological and pathological processes [1,2]. S-nitrosylation is one of the key mechanisms by which NO regulates the function of various target proteins is through the coupling a nitroso moiety from NO-derived metabolites to a reactive cysteine leading to the formation of a S-nitrosothiol (SNO) [3]. Modafinil, dalfampridine, baclofen, diazepam, gabapentin, and opioids) are used for symptomatic treatment of disability and symptoms, but these do not improve disease outcome [11]. This chronic immune-mediated disease potentially requires more definitive symptomatic and disease-modifying therapies. Recent studies have reported that SNOs accumulate in brain white matter of MS patients, indicating that the occurrence of protein S-nitrosylation correlates with the inflammatory demyelinating disorders in MS patients [8]. J Clin Cell Immunol 4: 147. doi:10.4172/2155-9899.1000147
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