Fig. 2

ER stress and human diseases triggered by misfolded protein aggregates. Environmental conditions, such as genetic mutations, hypoxia, and oxidative stress, disrupt ER homeostasis, leading to protein misfolding and accumulation. This, in turn, induces ER stress and expedites the build-up of disease-associated protein aggregates. The activation of the UPR signaling pathway serves to alleviate ER stress. However, when sustained ER stress surpasses the adaptive response capacity to manage protein misfolding, it can culminate in cell death, inflammation, and the proliferation of cancer cells, consequently contributing to disease progression. (ER stress, endoplasmic reticulum stress; UPR, unfolded protein response; PERK, protein kinase R-like endoplasmic reticulum kinase; IRE1, inositol-requiring enzyme 1; ATF6, activating transcription factor 6; Bip, immunoglobulin binding protein; eIF2α, eukaryotic initiation factor 2α.)