Sestrin-2 also known as Hi95 is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
that in humans is encoded by the ''SESN2''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.
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
Ketamine is a dissociative anesthetic used medically for induction and maintenance of anesthesia. It is also used as a recreational drug. It is one of the safest anesthetics, as, in contrast with opiates, ether, and propofol, it suppresses ne ...
has been found to activate the
mammalian target of rapamycin complex 1 (mTORC1) pathway in the
medial prefrontal cortex (mPFC) of the
brain
A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...
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.
is a
ligand
In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's electr ...
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
References
Further reading
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