S-nitrosothiol pathway (SNO pathway)

The S-nitrosothiol pathway is a fundamental biochemical system responsible for the post-translational modification of proteins through S-nitrosylation, where a nitric oxide (NO) moiety is attached to specific cysteine residues (Foster et al., 2003, PubMed). This pathway acts as a key mediator of nitric oxide signaling, independent of the classical cGMP pathway, and regulates a wide array of physiological functions including smooth muscle relaxation, metabolic homeostasis, and immune cell activation (Stamler et al., 2001, Cell). The primary regulatory enzyme in this pathway is S-nitrosoglutathione reductase (GSNOR), which controls the levels of S-nitrosoglutathione (GSNO), the most abundant endogenous S-nitrosothiol and a critical NO reservoir (Liu et al., 2004, Nature). Dysregulation of S-nitrosothiol levels is linked to the pathogenesis of respiratory diseases like asthma and cystic fibrosis, as well as cardiovascular and neurodegenerative conditions (Que et al., 2005, Science). Pharmacological intervention typically involves the use of GSNOR inhibitors, such as Cavosonstat, which aim to increase S-nitrosothiol bioavailability to exert anti-inflammatory and bronchodilatory effects (Green et al., 2012, Journal of Clinical Investigation). By preserving S-nitrosylated proteins, these drugs help restore normal cellular signaling and protect against oxidative and nitrosative stress-induced damage (Marozkina and Gaston, 2012, Methods in Enzymology).

Other names

S-nitrosylation pathwaySNO signalingNitrosative signaling pathwayS-nitrosoglutathione (GSNO) pathway

Inhibition of S-nitrosoglutathione reductase (GSNOR) to increase the concentration of S-nitrosoglutathione and other S-nitrosothiols, thereby enhancing S-nitrosylation-dependent signaling and cytoprotection.