Ferruginol prevents degeneration of dopaminergic neurons by enhancing clearance of α-synuclein in neuronal cells

被引：7
作者：
Wang, Xiaohong [1 ,2 ]
Cao, Guiyun [1 ,2 ]
Ding, Dongyi [1 ,2 ]
Li, Fei [1 ]
Zhao, Xuesong [1 ]
Wang, Jiahua [1 ]
Yang, Yang [1 ]
机构：
[1] Yangzhou Univ, Sch Med, Yangzhou, Jiangsu, Peoples R China
[2] Jiangsu Coinnovat Ctr Prevent & Control Important, Yangzhou 225009, Jiangsu, Peoples R China
来源：
FITOTERAPIA | 2022年 / 156卷
基金：
中国国家自然科学基金;
关键词：
Parkinson's disease; Ferruginol; alpha-Synuclein; A53T; Dopamine; DITERPENES; MECHANISM; SURVIVAL; ABIETANE; ROOTS;
D O I：
10.1016/j.fitote.2021.105066
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Lewy bodies are characteristic spherical inclusions in Parkinson's disease (PD) that are formed by alpha-synuclein fibrils. Ferruginol (Fer) is an amonomeric compound isolated from a traditional Chinese herb. Here, we show that Fer exerted potent neuroprotective effects in both in vitro and in vivo PD models. Neuronal cells transfected with A53T mutant (A53T) alpha-synuclein plasmids and treated with Fer exhibited attenuated the cytotoxicity induced by pathogenic A53T alpha-synuclein overexpression. Further, when we transfected neuronal cells with siRNA-SNCA (alpha-synuclein) plasmids and incubated them with Fer, the protective role of Fer decreased. We also found that Fer was a potent alpha-synuclein inhibitor in neuronal cells, which promotes the clearance of alpha synuclein in dopaminergic neurons exposed to 1-Methyl-4-phenylpyridinium (MPP +). Fer could inhibit abnormal alpha-synuclein aggregation and dopaminergic neuron depletion in A53T-Tg mice, suggesting that a role for Fer in alpha-synuclein accumulation and nigrostriatal pathway injury. Our study revealed that Fer strongly alleviated neurodegeneration by promoting alpha-synuclein clearance, indicating a neuroprotective role against alpha-synuclein oligomer-induced neurodegeneration, which makes it a promising candidate for the treatment of PD and other neurodegenerative diseases.
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页数：10
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