Corynoxine promotes TFEB/TFE3-mediated autophagy and alleviates Aß pathology in Alzheimer's disease models.
Acta Pharmacol Sin
; 45(5): 900-913, 2024 May.
Article
in En
| MEDLINE
| ID: mdl-38225393
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 Aß pathology in AD models.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Autophagy
/
Disease Models, Animal
/
Transient Receptor Potential Channels
/
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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Alzheimer Disease
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
/
Male
Language:
En
Year:
2024
Type:
Article