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Oxidative Medicine and Cellular Longevity
Volume 2017, Article ID 3296294, 10 pages
https://doi.org/10.1155/2017/3296294
Review Article

Sestrin2 as a Novel Biomarker and Therapeutic Target for Various Diseases

1College of Pharmacy, Qatar University, P.O. Box 2713, Doha, Qatar
2Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
3Department of Biological and Environmental Sciences, College of Arts and Sciences, Qatar University, P.O. Box 2713, Doha, Qatar
4Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
5School of Medicine, University of Texas Health Sciences Center at San Antonio, San Antonio, TX, USA

Correspondence should be addressed to Shankar Munusamy; aq.ude.uq@ymasunum.raknahs

Received 4 March 2017; Accepted 3 May 2017; Published 11 June 2017

Academic Editor: Alexander N. Orekhov

Copyright © 2017 Mazhar Pasha et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Sestrin2 (SESN2), a highly conserved stress-inducible metabolic protein, is known to repress reactive oxygen species (ROS) and provide cytoprotection against various noxious stimuli including genotoxic and oxidative stress, endoplasmic reticulum (ER) stress, and hypoxia. Studies demonstrate that the upregulation of Sestrin2 under conditions of oxidative stress augments autophagy-directed degradation of Kelch-like ECH-associated protein 1 (Keap1), which targets and breaks down nuclear erythroid-related factor 2 (Nrf2), a key regulator of various antioxidant genes. Moreover, ER stress and hypoxia are shown to induce Sestrins, which ultimately reduce cellular ROS levels. Sestrin2 also plays a pivotal role in metabolic regulation through activation of the key energy sensor AMP-dependent protein kinase (AMPK) and inhibition of mammalian target of rapamycin complex 1 (mTORC1). Other downstream effects of Sestrins include autophagy activation, antiapoptotic effects in normal cells, and proapoptotic effects in cancer cells. As perturbations in the aforementioned pathways are well documented in multiple diseases, Sestrin2 might serve as a potential therapeutic target for various diseases. Thus, the aim of this review is to discuss the upstream regulators and the downstream effectors of Sestrins and to highlight the significance of Sestrin2 as a biomarker and a therapeutic target in diseases such as metabolic disorders, cardiovascular and neurodegenerative diseases, and cancer.