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Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2019.00977

Endoplasmic reticulum stress activates UPR signaling and mediates inflammation, obesity and cardiac dysfunction: Therapeutic and molecular approach

  • 1Taylor's University, Malaysia
  • 2Liverpool John Moores University, United Kingdom
  • 3University of Canberra, Australia
  • 4School of Medicine, Taylor's University, Malaysia

Obesity has been implicated as a risk factor for insulin resistance and cardiovascular diseases (CVDs). Although the association between obesity and CVD is a well-established phenomenon, the precise mechanisms remain incompletely understood. This has led to a relative paucity of therapeutic measures for the prevention and treatment of CVD and associated metabolic disorders. Recent studies have shed light on the pivotal role of prolonged endoplasmic reticulum stress (ERS)-initiated activation of the unfolded protein response (UPR), and the ensuing chronic low-grade inflammation, and altered insulin signaling in promoting obesity-compromised cardiovascular system (CVS). In this aspect, potential ways of attenuating ERS-initiated UPR signaling seems a promising avenue for therapeutic interventions. We review intersecting role of obesity-induced ERS, chronic inflammation, insulin resistance, and oxidative stress in the discovery of targeted therapy. Moreover, this review highlights the current progress and strategies on therapeutics being explored in preclinical and clinical research to modulate ERS and UPR signaling.

Keywords: Endoplasmic Reticulum Stress, unfolded protein response (UPR), Insulin resisitance, Obesity, Oxidative Stress

Received: 15 May 2019; Accepted: 31 Jul 2019.

Edited by:

Issy Laher, University of British Columbia, Canada

Reviewed by:

Andrea Sorrentino, Brigham and Women's Hospital, Harvard Medical School, United States
Jeffrey G. Dickhout, McMaster University, Canada  

Copyright: © 2019 Amen, Sarker, Ghildyal and Arya. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Aditya Arya, Taylor's University, Subang Jaya, 47500, Selangor Darul Ehsan, Malaysia, aditya.arya@taylors.edu.my