词条 | SESN2 |
释义 |
FunctionThis 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. 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][5] LigandsThe 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.[6] 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.[6] 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.[6] See also
References1. ^{{cite journal | vauthors = 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 | title = PA26 is a candidate gene for heterotaxia in humans: identification of a novel PA26-related gene family in human and mouse | journal = Hum Genet | volume = 112 | issue = 5–6 | pages = 573–80 |date=Apr 2003 | pmid = 12607115 | pmc = | doi = 10.1007/s00439-003-0917-5 }} 2. ^{{cite journal | vauthors = 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 | title = Identification of a novel stress-responsive gene Hi95 involved in regulation of cell viability | journal = Oncogene | volume = 21 | issue = 39 | pages = 6017–31 |date=Aug 2002 | pmid = 12203114 | pmc = | doi = 10.1038/sj.onc.1205877 }} 3. ^1 2 {{cite web | title = Entrez Gene: SESN2 sestrin 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=83667| accessdate = }} 4. ^{{cite journal | vauthors = Lee JH, Bodmer R, Bier E, Karin M | title = Sestrins at the crossroad between stress and aging | journal = Aging | volume = 2 | issue = 6 | pages = 369–74 |date=June 2010 | pmid = 20606249 | pmc = 2919257 | doi = 10.18632/aging.100157| url = }} 5. ^{{cite journal | vauthors = Lee JH, Budanov AV, Karin M | title = Sestrins orchestrate cellular metabolism to attenuate aging | journal = Cell Metab | volume = 18 | issue = 6 | pages = 792–801 |date=Dec 2013 | pmid = 24055102 | pmc = 3858445 | doi = 10.1016/j.cmet.2013.08.018 }} 6. ^1 2 {{cite journal | vauthors = Duman RS | title = Ketamine and rapid-acting antidepressants: a new era in the battle against depression and suicide | journal = F1000Res | volume = 7 | issue = | pages = | date = 2018 | pmid = 29899972 | pmc = 5968361 | doi = 10.12688/f1000research.14344.1 | url = }} Further reading{{refbegin | 2}}
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