Figure 3.

Neuronal survival and death signal complexes and downstream pathways associated with NMDARs. (a) Post-synaptic activity promotes neuronal survival via increasing the activation of the GluN2A-mediated PI3K/Akt complex and the downstream pathway. In addition, BDNF and PTEN are prosurvival and negative regulation factors, respectively, operating downstream of the PI3K/Akt, thereby producing opposite effects. (b) During cerebral ischemia, the influx of calcium through GluN2B-containing NMDARs induces phosphorylation of DAPK1 and formats PSD95-GluN2B-nNOS complex contributing to massive NO production and activating their downstream targets. Moreover, the GluN2B-PSD93-SynGAP and GluN2B-TRPM complexes are activated by hyperfunctioning NMDARs leading to neuronal death. Some treatments have been developed to interfere with these death effects (depicted in polygons).