Endoplasmic reticulum stress: a master regulator of metabolic syndrome

Mohan, Sreelekshmi and R, Preetha Rani M. and Brown, Lindsay and Ayyappan, Prathapan and G, Raghu K. (2019) Endoplasmic reticulum stress: a master regulator of metabolic syndrome. European Journal of Pharmacology, 860 (172553). pp. 1-10. ISSN 0014-2999

Abstract

Endoplasmic reticulum (ER) stress, a change in the ER homeostasis, leads to initiation of the unfolded protein response (UPR). The primary functions of the UPR are to restore the ER's physiological activity and coordinate the apoptotic and adaptive responses. Pathophysiological conditions that augment ER stress include hypoxia, misfolded and/or mutated protein accumulation, and high glucose. Prolonged ER stress is a critical factor in the pathogenesis of metabolic syndrome including type 2 diabetes mellitus, cardiovascular diseases, atherosclerosis, obesity, and fatty liver disease. UPR is a complex homeostatic pathway between newly synthesized proteins and their maturation, although the regulatory mechanisms contributing to the UPR and the possible therapeutic strategies are yet to be clarified. Therefore, a comprehensive understanding of the underlying molecular mechanisms is necessary to develop therapeutic interventions targeting ER stress response. In this review, we discuss the role of ER stress and UPR signaling in the pathogenesis of metabolic syndrome, highlighting the main functions of UPR components. We have emphasized the use of novel small molecular chemical chaperones, considered as modulators of ER stress. The initial studies with these chemical chaperones are promising, but detailed studies are required to define their efficacy and adverse effects during therapeutic use in humans.


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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Additional Information: Published version cannot be displayed due to copyright restrictions.
Faculty/School / Institute/Centre: Current - Faculty of Health, Engineering and Sciences - School of Health and Wellbeing (1 Jan 2015 -)
Faculty/School / Institute/Centre: Current - Faculty of Health, Engineering and Sciences - School of Health and Wellbeing (1 Jan 2015 -)
Date Deposited: 19 Aug 2019 05:15
Last Modified: 25 Sep 2019 05:59
Uncontrolled Keywords: ER stress; unfolded protein response; diabetes; obesity; cardiovascular diseases; liver
Fields of Research : 11 Medical and Health Sciences > 1115 Pharmacology and Pharmaceutical Sciences > 111501 Basic Pharmacology
Socio-Economic Objective: E Expanding Knowledge > 97 Expanding Knowledge > 970111 Expanding Knowledge in the Medical and Health Sciences
Identification Number or DOI: 10.1016/j.ejphar.2019.172553
URI: http://eprints.usq.edu.au/id/eprint/36832

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