Endoplasmic reticulum stress-induced apoptotic pathway

The endoplasmic reticulum stress-induced apoptotic pathway is a conserved cellular mechanism activated in response to prolonged or unresolvable ER stress, typically triggered by misfolded protein accumulation, calcium dysregulation, oxidative stress, or energy imbalance[1][2][3]. The unfolded protein response (UPR) initially aims to restore homeostasis by halting protein translation, increasing chaperone expression, and enhancing degradation of misfolded proteins (ERAD). If stress persists, signaling switches to pro-apoptotic outputs through molecules such as CHOP/GADD153 (inducing pro-apoptotic genes and downregulating anti-apoptotic BCL2 family members), JNK (facilitating mitochondrial apoptosis), and caspases (execution phase)[1][2][3][4]. This switch is central to pathophysiology in many diseases marked by chronic cell stress, such as neurodegeneration, metabolic disorders, and cancer.

Other names

ER stress-induced apoptosisER stress apoptotic pathwayunfolded protein response-mediated apoptosis

Inhibition or activation of UPR sensors (PERK, IRE1, ATF6), modulation of downstream effectors (CHOP, JNK, caspases), use of chemical chaperones to alleviate protein misfolding, antioxidants to reduce ER-induced oxidative stress, direct proteostasis modulation