TY  - JOUR
AU  - Guan Xin-jie
AU  - Deng Zhi-qiang
AU  - Liu Jia
AU  - Su Cheng-fu
AU  - Tong Benjamin Chun-Kit
AU  - Zhu Zhou
AU  - Sreenivasmurthy Sravan Gopalkrishnashetty
AU  - Kan Yu-xuan
AU  - Lu Ke-jia
AU  - Chu Carol Pui-Kei
AU  - Pi Rong-biao
AU  - Cheung King-ho
AU  - Iyaswamy Ashok
AU  - Song Ju-xian
AU  - Li Min
PY  - 2024
TI  - Corynoxine promotes TFEB/TFE3-mediated autophagy and alleviates Aβ pathology in Alzheimer’s disease models
JF  - Acta Pharmacologica Sinica; Vol 45, No 5 (May 2024): Acta Pharmacologica Sinica
Y2  - 2024
KW  - 
N2  - 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.
UR  - http://www.chinaphar.com/article/view/11015