Figure 1.

Unfolded protein response (UPR) pathways in the ER and small molecule interventions. Upon ER stress, the ER launches three adaptive pathways through IRE1α, PERK, and activating transcription factor 6 (ATF6), collectively called as the UPR, to restore proteostasis. All these three ER stress sensors activate signaling cascades, increasing protein-folding ability and decreasing ER stress. Small molecules targeting three key UPR signaling components are also indicated in the figure suggesting the sites for therapeutic interventions. Adapted and modified from Webster et al. (2017).