Skip to main content
. Author manuscript; available in PMC: 2017 Jan 1.
Published in final edited form as: Trends Pharmacol Sci. 2015 Dec 17;37(1):73–84. doi: 10.1016/j.tips.2015.10.002

Figure 1.

Figure 1

NO/S-nitrosylation signaling under physiological and pathological conditions in the central nervous system. Physiological activation of NMDA receptors localized at synapses triggers calcium influx through the NMDA receptor-associated ion channel and stimulates nNOS tethered to the NMDA receptor protein complex. Physiological (basal) levels of NO thus produced contribute to normal neuronal functions, e.g., via S-nitrosylation of NMDA receptors (SNO-NMDAR) to prevent their overactivation. Under pathological (neurodegenerative) conditions, excessive activation of extrasynaptic the NMDAR-nNOS pathway (or iNOS expression in glia cells) can lead to overproduction of NO. Under these conditions, excessive generation of ROS can also occur. These pathways cause aberrant SNO-protein formation, such as SNO-GAPDH and SNO-PDI, augmenting pathological processes; in some cases nitrosothiol formation is followed by reaction of the same cysteine residue with ROS to form –SOxH adducts (with × = 1–3).