1. Jiangsu Coinnovat Ctr Prevent & Control Important
2. Yangzhou Univ
折叠
Abstract
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.
NSTL