J Clin Invest. 2019 May 20;129(6):2207-2209. 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.
越来越多的证据表明，mTORC1 信号级联的改变与抑郁症的病理生理学有关，这表明直接调节 mTORC1 信号可能提供新的治疗潜力。在本期 JCI 中，Kato 及其同事报告称，通过激活 mTORC1 信号，最近开发的合成亮氨酸类似物 NV-5138 在大鼠模型中具有快速和持续的抗抑郁作用。研究人员还发现，NV-5138 的抗抑郁作用是通过上调脑源性神经营养因子 (BDNF) 信号介导的，并且 NV-5138 治疗在后内侧前额叶皮层产生快速的突触反应。这些发现强调了直接激活 mTORC1 信号作为治疗抑郁症的潜在药物干预措施。
