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


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
Issue number6
StatePublished - Jun 3 2019

ASJC Scopus subject areas

  • Medicine(all)

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