The endoplasmic-reticulum (ER) stress response constitutes a cellular process that is triggered by a variety of conditions that disturb folding of proteins in the ER. Eukaryotic cells have developed an evolutionarily conserved adaptive mechanism, the unfolded protein response (UPR), which aims to clear unfolded proteins and restore ER homeostasis. In cases where ER stress cannot be reversed, cellular functions deteriorate, often leading to cell death. Accumulating evidence implicates ER stress-induced cellular dysfunction and cell death as major contributors to many diseases, making modulators of ER stress pathways potentially attractive targets for therapeutics discovery. Here, we summarize recent advances in understanding the diversity of molecular mechanisms that govern ER stress signaling in health and disease. This article is part of a Special Section entitled: Cell Death Pathways.
Keywords: AGE; ALS; AMD; ARE; ASK1; ATF/cAMP response elements; ATF4; ATF6; BAG; BAR; BI-1; Bcl-2 associated athanogene; BiP; CASR; CHOP; CMV; CRE; Cell death mechanisms; DRP-1; Diseases; ER; ER Stress; ER antigen peptide transporter 1; ER stress-response element; ER-assisted degradation; ERAD; ERO1α; ERSE; GADD34; HCV; HFD; HO-1; HSV; IBD; IEC; IP(3)R; IRE1α; JNK; Jun-N-terminal kinase; MEF; MHC; NLRP; NOD-like receptor, (NLR) family pyrin domain-containing; NRF2; PDIA6; PERK; PKC; RIDD; RP; SNP; T2DM; TAP1; TLR; TXNIP; UPR; VEGF; X box-binding protein-1; XBP-1; activating transcription factor 4; activating transcription factor 6; advanced glycated end-products; age-related macular degeneration; amyotropic lateral sclerosis; antioxidant response elements; apoptotic-signaling kinase-1; bax-inhibitor 1; bifunctional apoptosis regulator; binding immunoglobulin protein; calcium-sensing receptor; cytomegalovirus; dynamin-related protein; elF2α; endoplasmic reticulum; endoplasmic reticulum oxidoreductase-1; eukaryotic translation initiation factor; growth arrest and DNA damage-inducible 34; heme oxygenase 1; hepatitis C virus; herpes simplex virus; high fat diet; inflammatory bowel disease; inositol triphosphate receptor; inositol-requiring protein-1; intestinal epithelial cells; major histocompatibility complex; mouse embryonic fibroblast; nuclear erythroid 2 p45-related factor 2; protein disulfide isomerase associated 6; protein kinase C; protein kinase RNA (PKR)-like ER kinase; regulated IRE1-dependent decay of mRNA; retinitis pigmentosa; single nucleotide polymorphism; thioredoxin-interacting protein; toll-like receptor; transcriptional factor C/EBP homologous protein; type 2 diabetes; unfolded protein response; vascular endothelial growth factor.