title: Targeting the unfolded protein response in disease.
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.
authors.affiliation: 1] 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.
authors.forename: Claudio
authors.initials: C
authors.lastname: Hetz
authors.forename: Eric
authors.initials: E
authors.lastname: Chevet
authors.forename: Heather P
authors.initials: HP
authors.lastname: Harding
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015195:Drug Design; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D006801:Humans; D058990:Molecular Targeted Therapy; D015398:Signal Transduction / Q000502:physiology; D056811:Unfolded Protein Response / Q000187:drug effects*