Targeting the unfolded protein response in disease

被引：843

作者：

Hetz, Claudio ^{[1
,2
]}

Chevet, Eric ^{[3
]}

Harding, Heather P. ^{[4
,5
]}

机构：

[1] Univ Chile, Fac Med, ICBM, Biomed Neurosci Inst,Program Cellular & Mol Biol, Santiago 7, Chile

[2] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA

[3] Univ Bordeaux Segalen, INSERM, U1053, French Natl Inst Hlth & Med Res, F-33000 Bordeaux, France

[4] Univ Cambridge, Metab Res Labs, Cambridge CB2 0QQ, England

[5] Univ Cambridge, Natl Inst Hlth Res, Cambridge Biomed Res Ctr, Cambridge CB2 0QQ, England

来源：

NATURE REVIEWS DRUG DISCOVERY | 2013年 / 12卷 / 09期

基金：

英国惠康基金;

关键词：

ENDOPLASMIC-RETICULUM-STRESS; SODIUM 4-PHENYLBUTYRATE PROTECTS; MOLECULAR CHAPERONE-INDUCER; TRANSCRIPTION FACTOR XBP-1; NEURONAL CELL-DEATH; ER STRESS; MESSENGER-RNA; EIF2-ALPHA DEPHOSPHORYLATION; TRANSMEMBRANE PROTEIN; DISULFIDE ISOMERASES;

D O I：

10.1038/nrd3976

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 [微生物学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页码：703 / 719

页数：17

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