2. Academic Validation
  3. Corynoxine promotes TFEB/TFE3-mediated autophagy and alleviates Aβ pathology in Alzheimer's disease models

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

  • Acta Pharmacol Sin. 2024 Jan 15. doi: 10.1038/s41401-023-01197-1.
Xin-Jie Guan 1 2,  Zhi-Qiang Deng 1 2,  Jia Liu 1 2,  Cheng-Fu Su 1 2,  Benjamin Chun-Kit Tong 1,  Zhou Zhu 1 2,  Sravan Gopalkrishnashetty Sreenivasmurthy 1 3,  Yu-Xuan Kan 1 2,  Ke-Jia Lu 1,  Carol Pui-Kei Chu 1,  Rong-Biao Pi 4,  King-Ho Cheung 1 2,  Ashok Iyaswamy 5 6,  Ju-Xian Song 7,  Min Li 8 9
Affiliations

Affiliations

  • 1 Mr. & Mrs. Ko Chi Ming Centre for Parkinson's Disease Research (CPDR), School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.
  • 2 Institute for Research and Continuing Education, Hong Kong Baptist University, Shenzhen, 518057, China.
  • 3 Department of Neurology, University of Texas Medical Branch, Galveston, TX, USA.
  • 4 School of Medicine, Sun Yat-sen University (Shenzhen), Shenzhen, 518107, China.
  • 5 Mr. & Mrs. Ko Chi Ming Centre for Parkinson's Disease Research (CPDR), School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China. ashokenviro@gmail.com.
  • 6 Institute for Research and Continuing Education, Hong Kong Baptist University, Shenzhen, 518057, China. ashokenviro@gmail.com.
  • 7 Medical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China. juxian.song@gmail.com.
  • 8 Mr. & Mrs. Ko Chi Ming Centre for Parkinson's Disease Research (CPDR), School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China. limin@hkbu.edu.hk.
  • 9 Institute for Research and Continuing Education, Hong Kong Baptist University, Shenzhen, 518057, China. limin@hkbu.edu.hk.
PMID: 38225393 DOI: 10.1038/s41401-023-01197-1
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.

Keywords

Alzheimer’s disease; TFEB/TFE3; autophagy; calcium; corynoxine.

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