Necroptosis-related diseases are regulated by the unfolded protein response during endoplasmic reticulum stress

In recent years, research has highlighted that necroptosis plays a significant role in various diseases, suggesting that studying the pathways of necroptosis may offer novel avenues for developing treatments for these conditions. The classical necroptosis pathway involves the activation and phosphorylation of RIPK1, RIPK3, and MLKL. Moreover, the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress is crucial in regulating necroptosis. ER stress impacts cell survival by activating the UPR, which subsequently influences downstream PERK, IRE1α, and ATF6 pathways. This paper will elucidate the signaling mechanisms within the classical necroptosis pathway and the three UPR pathways involved in ER stress. Additionally, this review will focus on the functional mechanisms of the UPR pathways in necroptosis and the latest research advancements on how these pathways regulate necroptosis and influence the progression of related diseases.