@article{APS11015,
author = {Xin-jie Guan and Zhi-qiang Deng and Jia Liu and Cheng-fu Su and Benjamin Chun-Kit Tong and Zhou Zhu and Sravan Gopalkrishnashetty Sreenivasmurthy and Yu-xuan Kan and Ke-jia Lu and Carol Pui-Kei Chu and Rong-biao Pi and King-ho Cheung and Ashok Iyaswamy and Ju-xian Song and Min Li},
title = {Corynoxine promotes TFEB/TFE3-mediated autophagy and alleviates Aβ pathology in Alzheimer’s disease models},
journal = {Acta Pharmacologica Sinica},
volume = {45},
number = {5},
year = {2024},
keywords = {},
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.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/11015}
}