NV-5138 as a fast-acting antidepressant via direct activation of mTORC1 signaling

Yuto Hasegawa, Xiaolei Zhu, Atsushi Kamiya

Research output: Contribution to journalReview article

Abstract

Growing evidence implicates altered mTORC1 signaling cascades in the pathophysiology of depression, suggesting that direct modulation of mTORC1 signaling may offer novel therapeutic potential. In this issue of the JCI, Kato and colleagues reported that administration of NV-5138, a recently developed synthetic leucine analog, has a rapid and sustained antidepressant action in rat models via activation of mTORC1 signaling. The investigators also found that the antidepressant effect of NV-5138 is mediated by upregulation of brain-derived neurotrophic factor (BDNF) signaling and that NV-5138 treatment produces rapid synaptic responses in the medial prefrontal cortex. These findings highlight the direct activation of mTORC1 signaling as a potential pharmacological intervention for the treatment of depression.

Original languageEnglish (US)
Pages (from-to)2207-2209
Number of pages3
JournalJournal of Clinical Investigation
Volume129
Issue number6
DOIs
StatePublished - Jun 3 2019

Fingerprint

Antidepressive Agents
Brain-Derived Neurotrophic Factor
Prefrontal Cortex
Leucine
Up-Regulation
Research Personnel
Pharmacology
mechanistic target of rapamycin complex 1
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

Cite this

NV-5138 as a fast-acting antidepressant via direct activation of mTORC1 signaling. / Hasegawa, Yuto; Zhu, Xiaolei; Kamiya, Atsushi.

In: Journal of Clinical Investigation, Vol. 129, No. 6, 03.06.2019, p. 2207-2209.

Research output: Contribution to journalReview article

@article{7329729e5d424436b829d61e3721b1ba,
title = "NV-5138 as a fast-acting antidepressant via direct activation of mTORC1 signaling",
abstract = "Growing evidence implicates altered mTORC1 signaling cascades in the pathophysiology of depression, suggesting that direct modulation of mTORC1 signaling may offer novel therapeutic potential. In this issue of the JCI, Kato and colleagues reported that administration of NV-5138, a recently developed synthetic leucine analog, has a rapid and sustained antidepressant action in rat models via activation of mTORC1 signaling. The investigators also found that the antidepressant effect of NV-5138 is mediated by upregulation of brain-derived neurotrophic factor (BDNF) signaling and that NV-5138 treatment produces rapid synaptic responses in the medial prefrontal cortex. These findings highlight the direct activation of mTORC1 signaling as a potential pharmacological intervention for the treatment of depression.",
author = "Yuto Hasegawa and Xiaolei Zhu and Atsushi Kamiya",
year = "2019",
month = "6",
day = "3",
doi = "10.1172/JCI129702",
language = "English (US)",
volume = "129",
pages = "2207--2209",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "6",

}

TY - JOUR

T1 - NV-5138 as a fast-acting antidepressant via direct activation of mTORC1 signaling

AU - Hasegawa, Yuto

AU - Zhu, Xiaolei

AU - Kamiya, Atsushi

PY - 2019/6/3

Y1 - 2019/6/3

N2 - Growing evidence implicates altered mTORC1 signaling cascades in the pathophysiology of depression, suggesting that direct modulation of mTORC1 signaling may offer novel therapeutic potential. In this issue of the JCI, Kato and colleagues reported that administration of NV-5138, a recently developed synthetic leucine analog, has a rapid and sustained antidepressant action in rat models via activation of mTORC1 signaling. The investigators also found that the antidepressant effect of NV-5138 is mediated by upregulation of brain-derived neurotrophic factor (BDNF) signaling and that NV-5138 treatment produces rapid synaptic responses in the medial prefrontal cortex. These findings highlight the direct activation of mTORC1 signaling as a potential pharmacological intervention for the treatment of depression.

AB - Growing evidence implicates altered mTORC1 signaling cascades in the pathophysiology of depression, suggesting that direct modulation of mTORC1 signaling may offer novel therapeutic potential. In this issue of the JCI, Kato and colleagues reported that administration of NV-5138, a recently developed synthetic leucine analog, has a rapid and sustained antidepressant action in rat models via activation of mTORC1 signaling. The investigators also found that the antidepressant effect of NV-5138 is mediated by upregulation of brain-derived neurotrophic factor (BDNF) signaling and that NV-5138 treatment produces rapid synaptic responses in the medial prefrontal cortex. These findings highlight the direct activation of mTORC1 signaling as a potential pharmacological intervention for the treatment of depression.

UR - http://www.scopus.com/inward/record.url?scp=85066630278&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85066630278&partnerID=8YFLogxK

U2 - 10.1172/JCI129702

DO - 10.1172/JCI129702

M3 - Review article

C2 - 31107245

AN - SCOPUS:85066630278

VL - 129

SP - 2207

EP - 2209

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 6

ER -