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Current Protein & Peptide Science


ISSN (Print): 1389-2037
ISSN (Online): 1875-5550

Review Article

Endoplasmic Reticulum Stress Signaling Pathways: Activation and Diseases

Author(s): Zhi Zheng, Yuxi Shang, Jiahui Tao, Jun Zhang* and Bingdong Sha*

Volume 20 , Issue 9 , 2019

Page: [935 - 943] Pages: 9

DOI: 10.2174/1389203720666190621103145

Price: $65


Secretory and membrane proteins are folded in the endoplasmic reticulum (ER) prior to their exit. When ER function is disturbed by exogenous and endogenous factors, such as heat shock, ultraviolet radiation, hypoxia, or hypoglycemia, the misfolded proteins may accumulate, promoting ER stress. To rescue this unfavorable situation, the unfolded protein response is activated to reduce misfolded proteins within the ER. Upon ER stress, the ER transmembrane sensor molecules inositol-requiring enzyme 1 (IRE1), RNA-dependent protein kinase (PKR)-like ER kinase (PERK), and activating transcription factor 6, are activated. Here, we discuss the mechanisms of PERK and IRE1 activation and describe two working models for ER stress initiation: the BiP-dependent model and the ligand-driven model. ER stress activation has been linked to multiple diseases, including cancers, Alzheimer’s disease, and diabetes. Thus, the regulation of ER stress may provide potential therapeutic targets for these diseases.

Keywords: ER stress, unfolded protein response, activation mechanism, cancer, Alzheimer's disease, diabetes.

Graphical Abstract
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