Sestrin-2 also known as Hi95 is a
protein that in humans is encoded by the ''SESN2''
gene.
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.
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.
Ligands
The
NMDA receptor antagonist ketamine has been found to activate the
mammalian target of rapamycin complex 1
mTORC1, also known as mammalian target of rapamycin complex 1 or mechanistic target of rapamycin complex 1, is a protein complex that functions as a nutrient/energy/redox sensor and controls protein synthesis.
mTOR Complex 1 (mTORC1) is comp ...
(mTORC1) pathway in the
medial prefrontal cortex (mPFC) of the
brain as an essential downstream mechanism in the mediation of its
rapid-acting antidepressant
Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, heada ...
effects.
NV-5138
NV-5138 is an orally and centrally active small-molecule drug which is under development by Navitor Pharmaceuticals for the treatment of major depressive disorder (MDD). It directly and selectively activates the mammalian target of rapamycin co ...
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.
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.
See also
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SESN1
Sestrin 1, also known as p53-regulated protein PA26, is a protein that in humans is encoded by the ''SESN1'' gene.
This gene encodes a member of the sestrin family. Sestrins are induced by the p53 tumor suppressor protein and play a role in the ...
References
Further reading
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