2019
DOI: 10.1172/jci126859
|View full text |Cite
|
Sign up to set email alerts
|

Sestrin modulator NV-5138 produces rapid antidepressant effects via direct mTORC1 activation

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
1
1
1
1

Citation Types

3
58
0

Year Published

2019
2019
2023
2023

Publication Types

Select...
10

Relationship

0
10

Authors

Journals

citations
Cited by 63 publications
(61 citation statements)
references
References 50 publications
3
58
0
Order By: Relevance
“…Clinical targeting of the mTOR pathway to rescue RGC degeneration may involve pharmacological activation of the pathway. Recently, a small molecule, NV-5138, has been shown to activate mTORC1 both in vivo and in vitro (Kato et al, 2019;Sengupta et al, 2019). Alternatively, to address the concern that pharmacological activation of the mTOR pathway may affect the function of other cell types because of its ubiquitous presence, RGCs could be targeted for silencing the TSC2 gene by adeno-associated virus sera 2 (AAV2) transduction, which is RGC specific in the adult retina (Hanlon et al, 2017;Harvey et al, 2009).…”
Section: Discussionmentioning
confidence: 99%
“…Clinical targeting of the mTOR pathway to rescue RGC degeneration may involve pharmacological activation of the pathway. Recently, a small molecule, NV-5138, has been shown to activate mTORC1 both in vivo and in vitro (Kato et al, 2019;Sengupta et al, 2019). Alternatively, to address the concern that pharmacological activation of the mTOR pathway may affect the function of other cell types because of its ubiquitous presence, RGCs could be targeted for silencing the TSC2 gene by adeno-associated virus sera 2 (AAV2) transduction, which is RGC specific in the adult retina (Hanlon et al, 2017;Harvey et al, 2009).…”
Section: Discussionmentioning
confidence: 99%
“…Lysine-specific demethylase 1 (LSD1) suppresses oxidized low-density lipoprotein (Ox-LDL)-induced inflammation by promoting Sestrin2-mediated PI3K/AKT/mTOR pathway activation (Zhuo et al, 2019). Recently, Navitor Pharmaceuticals developed Sestrin2-specific inhibitor, a leucine analog NV-5138, and try to treat the major depressive disorder (MDD) by activating mTORC1 in the brain (Hasegawa et al, 2019;Kato et al, 2019;Sengupta et al, 2019). However, one of the main causes of obesity, inflammation and metabolic disease is the hyperactivation of mTORC1, so the development of Sestrin2-specific activator compound or drug would be a potential therapeutic (Dong, 2015).…”
Section: Introduction Of Sestrinsmentioning
confidence: 99%
“…In vivo analysis of extracellular serotonin after administration of Alk-S-Cit. SSRIs increase the serotonin level in the synaptic cleft by binding to SERT, especially in the medial prefrontal cortex, a brain region implicated in antidepressant effects (24). The medial prefrontal cortex receives inputs from the dorsal raphe nucleus, the largest serotonergic nucleus in the murine brain, and exhibits increased levels of extracellular serotonin after the administration of SSRIs (25).…”
Section: Resultsmentioning
confidence: 99%