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Nat Rev Drug Discov. 2008 Dec;7(12):1013-30. doi: 10.1038/nrd2755.

Cell death and endoplasmic reticulum stress: disease relevance and therapeutic opportunities.

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  • 1Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, California 92037, USA.

Abstract

The accumulation of unfolded proteins in the endoplasmic reticulum (ER) represents a cellular stress induced by multiple stimuli and pathological conditions. These include hypoxia, oxidative injury, high-fat diet, hypoglycaemia, protein inclusion bodies and viral infection. ER stress triggers an evolutionarily conserved series of signal-transduction events, which constitutes the unfolded protein response. These signalling events aim to ameliorate the accumulation of unfolded proteins in the ER; however, when these events are severe or protracted they can induce cell death. With the increasing recognition of an association between ER stress and human diseases, and with the improved understanding of the diverse underlying molecular mechanisms, novel targets for drug discovery and new strategies for therapeutic intervention are beginning to emerge.

PMID:
19043451
DOI:
10.1038/nrd2755
[PubMed - indexed for MEDLINE]
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