Fig. 1: Schematic representation of ER and UPR under stress condition and putative current therapeutic approaches
Diagram representing the ER and UPR in condition of ER stress within the cell. ER stress-mediated accumulation of misfolded proteins triggers the activation of the PERK, IRE1α and ATF6 stress sensor through the molecular chaperone Bip. Prolonged insults, secondary ER stress and the sustained UPR activation result in cellular apoptosis. Mitochondria-ER interaction modulates the Ca2+ content in the mitochondria and secondary activation of autophagy/apoptosis processes. Putative treatment strategies modulating ER/UPR pathways towards cell survival are mapped: compounds 1 and 2 interfere with the PERK-Eif2 axis, while compounds 3 and 4 interfere with chaperones functions.