Skip to main content
. 2022 Apr 11;23(8):4243. doi: 10.3390/ijms23084243

Figure 2.

Figure 2

The NO signaling pathway, resulting in neuronal cell death during brain ischemia and reperfusion. During brain I/R, NMDAR forms a complex with nNOS through PSD95, resulting in nNOS activation and NO synthesis [20,21,22,23]. NO produced by nNOS activates c-Src through phosphorylation to inhibit the activity of NMDAR [32]. NO also phosphorylates downstream signaling molecules, including ASK, MLK3, and p38, which subsequently activates their downstream signaling proteins and finally stimulates the cell apoptosis pathway, resulting in cell death [24,25,26,27,28]. NO activates CaMKII through S-nitrosylation, resulting in neuronal damage [16]. NMDAR, N-methyl-D-aspartate receptor; nNOS, neuronal NOS; PSD95, postsynaptic density protein 95; ASK, apoptosis signal-regulating kinase; MLK3, mixed linage kinase 3; CaMKII, Ca2+/calmodulin-dependent protein kinase II; MKK4/7, mitogen-activated protein kinase kinase 4/7; JNK3, c-jun N-terminal kinase 3. Reproduced with permission from the European Review for Medical and Pharmacological Sciences, 2019, 23, 7674–7683. Copyright © 2022 Eur Rev Med Phamarcol Sci.