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Nat Rev Drug Discov. 2013 Sep;12(9):703-19. doi: 10.1038/nrd3976.

Targeting the unfolded protein response in disease.

Author information

  • 11] Biomedical Neuroscience Institute, Program of Cellular and Molecular Biology, ICBM, Faculty of Medicine, University of Chile, 1027 Independencia, PO Box 70086, Santiago, Chile. [2] Department of Immunology and Infectious Diseases, Harvard School of Public Health, 651 Huntington Avenue, Boston, Massachusetts 02115, USA.

Abstract

Stress induced by the accumulation of unfolded proteins in the endoplasmic reticulum (ER) is a feature of specialized secretory cells and is also observed in many diseases, including cancer, diabetes, autoimmune conditions, liver disorders, obesity and neurodegenerative disorders. Cellular adaptation to ER stress is achieved by the activation of the unfolded protein response, which is an integrated signal transduction pathway that modulates many aspects of ER physiology. When these mechanisms of adaptation are insufficient to handle the unfolded protein load, cells undergo apoptosis. Here, we discuss recent advances in the design of novel compounds and therapeutic strategies to manipulate levels of ER stress in disease.

PMID:
23989796
[PubMed - indexed for MEDLINE]
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