Rosmarinic acid protects against MPTP-induced toxicity and inhibits iron induced α-synuclein aggregation
Rosmarinic acid protects against MPTP-induced toxicity and inhibits iron induced α-synuclein aggregation
复制标题
迷迭香酸可防止 MPTP 诱导的毒性并抑制铁诱导的 α-突触核蛋白聚集
DOI：
10.1016/j.neuropharm.2018.09.042
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发表时间：
2019-01-01
影响因子：
4.7
通讯作者：
Xie, Junxia
中科院分区：
文献类型：
--
作者：
Qu, Le;Xu, Huamin;Xie, Junxia
Rosmarinic acid (RA) is a naturally occurring polyphenolic compound. In this study, we demonstrated that RA could protect against the degeneration of the nigrostriatal dopaminergic system in 1-methyl-4-phenyl-1,2,3,6-etrahydropyridine (MPTP)-induced mouse model of Parkinson's disease (PD). In addition, RA could inhibit MPTP-induced decrease of superoxide dismutase (SOD) and tyrosine hydroxylase (TH) and increase in nigral iron content. Further studies elucidated the effects of RA on iron-induced neurotoxicity and the possible underlying mechanisms in the SK-N-SH cells. Results showed that iron could induce a decrease in the mitochondrial transmembrane potential and result in alpha-synuclein aggregation in the SK-N-SH cells, which could be restored by RA pretreatment. Further results showed RA pretreatment could inhibit iron-induced a-synuclein aggregation by up-regulating hemeoxygenase-1 (HO-1). In addition, iron could increase the mRNA levels of a-synuclein via iron responsive element/iron regulatory protein (IRE/IRP) system. RA pretreatment could decrease the mRNA levels of alpha-synuclein by decreasing the protein levels of IRP1. These results indicated that RA protected against iron induced alpha-synuclein aggregation by up-regulating HO-1 and inhibiting a-synuclein expression.
