@article{APS10680,
author = {Zhou Zhu and Liang-feng Liu and Cheng-fu Su and Jia Liu and Benjamin Chun-Kit Tong and Ashok Iyaswamy and Senthilkumar Krishnamoorthi and Sravan Gopalkrishnashetty Sreenivasmurthy and Xin-jie Guan and Yu-xuan Kan and Wen-jian Xie and Chen-liang Zhao and King-ho Cheung and Jia-hong Lu and Jie-qiong Tan and Hong-jie Zhang and Ju-xian Song and Min Li},
title = {Corynoxine B derivative CB6 prevents Parkinsonian toxicity in mice by inducing PIK3C3 complex-dependent autophagy},
journal = {Acta Pharmacologica Sinica},
volume = {43},
number = {10},
year = {2022},
keywords = {},
abstract = {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+-treated PC12 cells, CB6 inhibited cell apoptosis and increased cell viability by inducing autophagy. In MPTP-induced mouse model of PD, oral administration of CB6 (10, 20 mg· kg−1· d−1, for 21 days) significantly improved motor dysfunction and prevented the loss of dopaminergic neurons in the striatum and substantia nigra pars compacta. Collectively, compound CB6 is a brain-permeable autophagy enhancer via PIK3C3 complex activation, which may help the prevention or treatment of PD.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/10680}
}