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Mediators of endoplasmic reticulum stress-induced apoptosis
Open accessAbstract
The efficient functioning of the endoplasmic reticulum (ER) is essential for most cellular activities and survival. Conditions that interfere with ER function lead to the accumulation and aggregation of unfolded proteins. ER transmembrane receptors detect the onset of ER stress and initiate the unfolded protein response (UPR) to restore normal ER function. If the stress is prolonged, or the adaptive response fails, apoptotic cell death ensues. Many studies have focused on how this failure initiates apoptosis, as ER stress-induced apoptosis is implicated in the pathophysiology of several neurodegenerative and cardiovascular diseases. In this review, we examine the role of the molecules that are activated during the UPR in order to identify the molecular switch from the adaptive phase to apoptosis. We discuss how the activation of these molecules leads to the commitment of death and the mechanisms that are responsible for the final demise of the cell.
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“Alterations of ER redox state may also influence the cell death machinery by inducing caspase-dependent apoptosis through the down-regulation of Bcl-2 protein, which physiologically blocks the apoptotic cell death [52]”
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The integrated stress response
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Role of ROS and RNS Sources in Physiological and Pathological Conditions
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Metadata
- Authors
- Szegezdi, E., Logue, S. E., Gorman, A. M., & Samali, A.
- Affiliations
- National University of Ireland (IE)
- Venue
- The EMBO Reports
- Published
- 2006-09-01
- Volume
- 7
- Issue
- 9
- Pages
- 880-885
- ISSN
- 1469-221X (ISSN-L)
- 1469-3178
- PMC
- PMC1559676
- OpenAlex
- W2133644385
- Cited by
- 2,345
- References
- 45
- Citations by year
- 2026: 42 · 2025: 85 · 2024: 121 · 2023: 129 · 2022: 147 · 2021: 126 · 2020: 147 · 2019: 139 · 2018: 154 · 2017: 140 · 2016: 140 · 2015: 140 · 2014: 137 · 2013: 134 · 2012: 124
- FWCI
- 5.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- EMBO Reports (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Arrow@dit (Dublin Institute of Technology) (submittedVersion)
- ARAN (University of Galway Research Repository) (Ollscoil na Gaillimhe – University of Galway) (submittedVersion, cc-by-nc-nd)
- Funders
- Science Foundation Ireland
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- endoplasmic reticulum stress, apoptosis, unfolded protein response, ER stress-induced apoptosis, unfolded proteins, neurodegenerative diseases, cardiovascular disease, cell death mechanisms
- MeSH terms
- Animals, Endoplasmic Reticulum, Humans, Models, Biological, Signal Transduction, Apoptosis, Protein Folding, Oxidative Stress, Molecular Chaperones, Protein Transport, Mice
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