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ER stress-induced cell death mechanisms
1Sanford-Burnham Medical Research Institute, La Jolla, CA, 92037, USA.
Biochimica Et Biophysica Acta
|July 16, 2013
Summary
Cellular endoplasmic-reticulum (ER) stress triggers the unfolded protein response (UPR) to restore homeostasis. Unresolved ER stress causes cell dysfunction and death, highlighting UPR pathways as therapeutic targets for disease.
Area of Science:
- Cellular Biology
- Molecular Biology
- Pathophysiology
Background:
- Endoplasmic-reticulum (ER) stress arises from conditions disrupting protein folding within the ER.
- Eukaryotic cells employ the unfolded protein response (UPR), an adaptive mechanism, to resolve ER stress and maintain homeostasis.
- Failure to resolve ER stress leads to cellular dysfunction and potential cell death.
Purpose of the Study:
- To summarize recent advancements in understanding ER stress signaling mechanisms.
- To explore the molecular intricacies of ER stress in both health and disease contexts.
- To highlight the role of ER stress in various pathological conditions.
Main Methods:
- Review of current scientific literature on ER stress and UPR.
- Analysis of molecular mechanisms governing ER stress signaling pathways.
- Synthesis of data linking ER stress to cellular dysfunction and disease pathogenesis.
Main Results:
- ER stress involves a complex signaling network aimed at restoring protein folding and ER function.
- The UPR encompasses multiple pathways that are activated under conditions of proteotoxic stress.
- Dysregulation of ER stress signaling is implicated in the progression of numerous diseases.
Conclusions:
- ER stress and the UPR are critical cellular processes with significant implications for human health.
- Modulators of ER stress pathways represent promising therapeutic targets for a range of diseases.
- Further research into the molecular mechanisms of ER stress is essential for advancing therapeutic strategies.
Keywords:
AGEALSAMDAREASK1ATF/cAMP response elementsATF4ATF6BAGBARBI-1Bcl-2 associated athanogeneBiPCASRCHOPCMVCRECell death mechanismsDRP-1DiseasesERER StressER antigen peptide transporter 1ER stress-response elementER-assisted degradationERADERO1αERSEGADD34HCVHFDHO-1HSVIBDIECIP(3)RIRE1αJNKJun-N-terminal kinaseMEFMHCNLRPNOD-like receptor, (NLR) family pyrin domain-containingNRF2PDIA6PERKPKCRIDDRPSNPT2DMTAP1TLRTXNIPUPRVEGFX box-binding protein-1XBP-1activating transcription factor 4activating transcription factor 6advanced glycated end-productsage-related macular degenerationamyotropic lateral sclerosisantioxidant response elementsapoptotic-signaling kinase-1bax-inhibitor 1bifunctional apoptosis regulatorbinding immunoglobulin proteincalcium-sensing receptorcytomegalovirusdynamin-related proteinelF2αendoplasmic reticulumendoplasmic reticulum oxidoreductase-1eukaryotic translation initiation factorgrowth arrest and DNA damage-inducible 34heme oxygenase 1hepatitis C virusherpes simplex virushigh fat dietinflammatory bowel diseaseinositol triphosphate receptorinositol-requiring protein-1intestinal epithelial cellsmajor histocompatibility complexmouse embryonic fibroblastnuclear erythroid 2 p45-related factor 2protein disulfide isomerase associated 6protein kinase Cprotein kinase RNA (PKR)-like ER kinaseregulated IRE1-dependent decay of mRNAretinitis pigmentosasingle nucleotide polymorphismthioredoxin-interacting proteintoll-like receptortranscriptional factor C/EBP homologous proteintype 2 diabetesunfolded protein responsevascular endothelial growth factor
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