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

• Published in: The Journal of clinical investigation Vol. 129; no. 6; pp. 2207 - 2209
• Main Authors: Hasegawa, Yuto, Zhu, Xiaolei, Kamiya, Atsushi
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 01-06-2019
• Subjects: Analysis; Animal models; Animals; Antidepressants; Antidepressive Agents; Biomedical research; Brain-Derived Neurotrophic Factor; Depression; Depression (Mood disorder); Health aspects; Kinases; Leucine; Mechanistic Target of Rapamycin Complex 1; Medical schools; Mental depression; Prefrontal cortex; Rats; Signal Transduction - drug effects; United States > US
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI129702

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.