香港浸会大学Min Li等研究人员合作发现，柯诺辛促进TFEB/TFE3介导的自噬并减轻阿尔茨海默病模型中Aβ的病理变化。2024年1月15日，国际知名学术期刊《中国药理学报》在线发表了这一成果。

研究人员表示，自噬功能受损是阿尔茨海默病（AD）发病机制中的一个关键因素。TFEB（转录因子EB）和TFE3（与IGHM增强子结合的转录因子3）是调节自噬和溶酶体生物发生的核转录因子。研究人员之前发现，中药复方柯诺辛（Cory）可通过激活自噬保护神经元免受帕金森病（PD）的侵害。

研究人员揭示了Cory对体内和体外注意力缺失症模型的影响。研究人员发现，Cory能改善5xFAD小鼠模型的学习和记忆功能，增加神经元自噬和溶酶体生物生成，降低致病性APP-CTF水平。Cory通过抑制AKT/mTOR信号传导和通过瞬时受体电位粘脂蛋白1（TRPML1）刺激溶酶体钙释放来激活TFEB/TFE3。此外，研究人员还证实，在N2aSwedAPP细胞中，敲低TFEB/TFE3可消除Cory诱导的APP-CTFs降解。研究结果表明，Cory能促进TFEB/TFE3介导的自噬，减轻AD模型中Aβ的病理变化。

附：英文原文

Title: Corynoxine promotes TFEB/TFE3-mediated autophagy and alleviates Aβ pathology in Alzheimer’s disease models

Author: Guan, Xin-jie, Deng, Zhi-qiang, Liu, Jia, Su, Cheng-fu, Tong, Benjamin Chun-Kit, Zhu, Zhou, Sreenivasmurthy, Sravan Gopalkrishnashetty, Kan, Yu-xuan, Lu, Ke-jia, Chu, Carol Pui-Kei, Pi, Rong-biao, Cheung, King-ho, Iyaswamy, Ashok, Song, Ju-xian, Li, Min

Issue&Volume: 2024-01-15

Abstract: Autophagy impairment is a key factor in Alzheimer’s disease (AD) pathogenesis. TFEB (transcription factor EB) and TFE3 (transcription factor binding to IGHM enhancer 3) are nuclear transcription factors that regulate autophagy and lysosomal biogenesis. We previously showed that corynoxine (Cory), a Chinese medicine compound, protects neurons from Parkinson’s disease (PD) by activating autophagy. In this study, we investigated the effect of Cory on AD models in vivo and in vitro. We found that Cory improved learning and memory function, increased neuronal autophagy and lysosomal biogenesis, and reduced pathogenic APP-CTFs levels in 5xFAD mice model. Cory activated TFEB/TFE3 by inhibiting AKT/mTOR signaling and stimulating lysosomal calcium release via transient receptor potential mucolipin 1 (TRPML1). Moreover, we demonstrated that TFEB/TFE3 knockdown abolished Cory-induced APP-CTFs degradation in N2aSwedAPP cells. Our findings suggest that Cory promotes TFEB/TFE3-mediated autophagy and alleviates Aβ pathology in AD models.

DOI: 10.1038/s41401-023-01197-1

Source: https://www.nature.com/articles/s41401-023-01197-1