Endoplasmic reticulum stress-induced apoptosis pathway

The **endoplasmic reticulum stress-induced apoptosis pathway** is a cellular signaling cascade activated when the protein-folding capacity of the ER is exceeded or compromised, leading to an accumulation of misfolded or unfolded proteins[3][4][6]. Cells respond by initiating the unfolded protein response (UPR) to restore homeostasis, mediated by three principal ER sensors: inositol-requiring enzyme 1 (IRE1), PERK (PKR-like ER kinase), and activating transcription factor 6 (ATF6)[3][4]. If ER stress is excessive or prolonged and adaptive mechanisms fail, UPR signaling switches from pro-survival to pro-apoptotic, engaging transcription factors (like CHOP) and BH3-only family proteins (such as DP5 and PUMA), as well as molecular pathways that culminate in mitochondrial outer membrane permeabilization, cytochrome c release, and caspase activation, leading to cell death[1][2][3][4][5][6]. Excessive ER stress-induced apoptosis contributes to tissue injury in various diseases, including cancer, neurodegeneration, diabetes, and ischemic damage[2][5]. **Note:** This entity represents a signaling pathway, not a discrete molecule, receptor, or conventional drug target. In drug discovery and pharmacology databases, only individual molecules (proteins, receptors, enzymes, transporters, etc.) are considered actionable targets. The ER stress-induced apoptosis pathway consists of multiple molecular targets (e.g., PERK, IRE1, ATF6, CHOP, BAX, caspases) but is not itself a molecule; therefore, it is not considered a therapeutic target as defined by standard nomenclature and ontology, and so entries such as interacting drugs, mechanism of action, biomarkers, and safety concerns should reference component molecules rather than the pathway as a whole[2][3][4][5][6].

Other names

ER stress-induced apoptotic pathwayER stress apoptosisunfolded protein response-induced apoptosisUPR-mediated apoptosis