SESN2

From English Wikipedia @ Freddythechick

An Error has occurred retrieving Wikidata item for infobox

Sestrin-2 also known as Hi95 is a protein that in humans is encoded by the SESN2 gene.[1][2][3]

Function

This gene encodes a member of the sestrin family of PA26-related proteins. The encoded protein may function in the regulation of cell growth and survival. This protein may be involved in cellular response to different stress conditions.[3][4] The Sestrins constitute a family of evolutionarily-conserved stress-inducible proteins that suppress oxidative stress and regulate adenosine monophosphate-dependent protein kinase (AMPK)-mammalian target of rapamycin (mTOR) signaling. By virtue of these activities, the Sestrins serve as important regulators of metabolic homeostasis.[5] Accordingly, inactivation of Sestrin genes in invertebrates resulted in diverse metabolic pathologies, including oxidative damage, fat accumulation, mitochondrial dysfunction and muscle degeneration that resemble accelerated tissue aging.[3][6]

Ligands

The NMDA receptor antagonist ketamine has been found to activate the mammalian target of rapamycin complex 1 (mTORC1) pathway in the medial prefrontal cortex (mPFC) of the brain as an essential downstream mechanism in the mediation of its rapid-acting antidepressant effects.[7] NV-5138 is a ligand and modulator of sestrin2, a leucine amino acid sensor and upstream regulatory pathway of mTORC1, and is under development for the treatment of depression.[7] The drug has been found to directly and selectively activate the mTORC1 pathway, including in the mPFC, and to produce rapid-acting antidepressant effects similar to those of ketamine.[7]

See also

References

  1. ^ Peeters H, Debeer P, Bairoch A, Wilquet V, Huysmans C, Parthoens E, Fryns JP, Gewillig M, Nakamura Y, Niikawa N, Van de Ven W, Devriendt K (Apr 2003). "PA26 is a candidate gene for heterotaxia in humans: identification of a novel PA26-related gene family in human and mouse". Hum Genet. 112 (5–6): 573–80. doi:10.1007/s00439-003-0917-5. PMID 12607115. S2CID 22257894.
  2. ^ Budanov AV, Shoshani T, Faerman A, Zelin E, Kamer I, Kalinski H, Gorodin S, Fishman A, Chajut A, Einat P, Skaliter R, Gudkov AV, Chumakov PM, Feinstein E (Aug 2002). "Identification of a novel stress-responsive gene Hi95 involved in regulation of cell viability". Oncogene. 21 (39): 6017–31. doi:10.1038/sj.onc.1205877. PMID 12203114. S2CID 7991114.
  3. ^ 3.0 3.1 3.2 "Entrez Gene: SESN2 sestrin 2".
  4. ^ Lee JH, Bodmer R, Bier E, Karin M (June 2010). "Sestrins at the crossroad between stress and aging". Aging. 2 (6): 369–74. doi:10.18632/aging.100157. PMC 2919257. PMID 20606249.
  5. ^ Gong L, Wang Z, Wang Z, Zhang Z (2021). "Sestrin2 as a Potential Target for Regulating Metabolic-Related Diseases". Front Endocrinol (Lausanne). 12: 751020. doi:10.3389/fendo.2021.751020. PMC 8595836. PMID 34803916.
  6. ^ Lee JH, Budanov AV, Karin M (Dec 2013). "Sestrins orchestrate cellular metabolism to attenuate aging". Cell Metab. 18 (6): 792–801. doi:10.1016/j.cmet.2013.08.018. PMC 3858445. PMID 24055102.
  7. ^ 7.0 7.1 7.2 Duman RS (2018). "Ketamine and rapid-acting antidepressants: a new era in the battle against depression and suicide". F1000Res. 7: 659. doi:10.12688/f1000research.14344.1. PMC 5968361. PMID 29899972.

Further reading