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AuthorPasha, Mazhar
AuthorEid, Ali H.
AuthorEid, Assaad A.
AuthorGorin, Yves
AuthorMunusamy, Shankar
Available date2017-06-12T07:25:28Z
Publication Date2017-06-11
Publication NameOxidative Medicine and Cellular Longevity
Identifierhttp://dx.doi.org/10.1155/2017/3296294
CitationMazhar Pasha, Ali H. Eid, Assaad A. Eid, Yves Gorin, and Shankar Munusamy, “Sestrin2 as a Novel Biomarker and Therapeutic Target for Various Diseases,” Oxidative Medicine and Cellular Longevity, vol. 2017, Article ID 3296294, 10 pages, 2017.
ISSN1942-0900
URIhttp://hdl.handle.net/10576/5565
AbstractSestrin2 (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.
SponsorThis publication was made possible by a NPRP award [NPRP8-1750-3-360] from the Qatar National Research Fund (a member of The Qatar Foundation). The statements made herein are solely the responsibility of the authors.
Languageen
PublisherHindawi
SubjectSestrins
Oxidative Stress
ER Stress
AMPK
mTOR
Autophagy
TitleSestrin2 as a Novel Biomarker and Therapeutic Target for Various Diseases
TypeArticle
Volume Number2017
ESSN1942-0994
dc.accessType Open Access


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