Figure 1.

The activation of UPR^ER in the neuronal cell. Under the imposed ER stress, a neuronal cell activates UPR^ER that starts with the release of GRP78 from its association with the luminal components of the three transmembrane transducers of UPR^ER: PERK, IRE1 and ATF6. GRP78 is recruited to the misfolded protein cargo. This stimulates all the three transducers in a series of events that disseminate their effect through transcriptional control of genes. PERK phosphorylates cytoplasmic eIF2 α that causes attenuation of global protein translation, paradoxically favors translation of ATF4 and activates Nrf2. Further IRE1 leads to XBP1 splicing and activation of JNK/NF-κB. ATF6 undergo proteolysis. All working in coherence, first ameliorates the stress, but later under chronic ER stress apoptotic pathway leads to cell death.