Corynoxine B derivative CB6 prevents Parkinsonian toxicity in mice by inducing PIK3C3 complex-dependent autophagy

Autor: Zhou Zhu, Liang-feng Liu, Cheng-fu Su, Jia Liu, Benjamin Chun-Kit Tong, Ashok Iyaswamy, Senthilkumar Krishnamoorthi, Sravan Gopalkrishnashetty Sreenivasmurthy, Xin-jie Guan, Yu-xuan Kan, Wen-jian Xie, Chen-liang Zhao, King-ho Cheung, Jia-hong Lu, Jie-qiong Tan, Hong-jie Zhang, Ju-xian Song, Min Li
Rok vydání: 2022
Předmět:
Zdroj: Acta Pharmacologica Sinica. 43:2511-2526
ISSN: 1745-7254
1671-4083
Popis: Increasing evidence shows that autophagy impairment is involved in the pathogenesis and progression of neurodegenerative diseases including Parkinson's disease (PD). We previously identified a natural alkaloid named corynoxine B (Cory B) as a neuronal autophagy inducer. However, its brain permeability is relatively low, which hinders its potential use in treating PD. Thus we synthesized various derivatives of Cory B to find more potent autophagy inducers with improved brain bioavailability. In this study, we evaluated the autophagy-enhancing effect of CB6 derivative and its neuroprotective action against PD in vitro and in vivo. We showed that CB6 (5-40 μM) dose-dependently accelerated autophagy flux in cultured N2a neural cells through activating the PIK3C3 complex and promoting PI3P production. In MPP
Databáze: OpenAIRE
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