Pramipexole (PPX) is a common drug for the treatment of Parkinson's disease. However, the mechanism allows PPX in the progression of Parkinson's disease remains largely unknown. This study aimed to investigate the role of PPX in 1-Methyl-4-phenylpyridinium (MPP+)-treated neuroblastoma cells and explore the interaction between PPX and miR-494-3p/brain derived neurotrophic factor (BDNF) axis. SK-N-SH and CHP 212 cells challenged by MPP+ were used as cellular model of Parkinson's disease and incubated with PPX. The expression levels of miR-494-3p and BDNF were measured by quantitative real-time polymerase chain reaction or western blot. Neurotoxicity was investigated by cell apoptosis, inflammatory response and oxidative stress. The target association between miR-494-3p and BDNF was confirmed by luciferase reporter and RNA immunoprecipitation assays. miR-494-3p expression was increased and BDNF level was decreased in MPP+-treated SK-N-SH and CHP 212 cells, which were reversed by introduction of PPX. Pramipexole attenuated cell apoptosis, inflammatory response and oxidative stress in MPP+-treated SK-N-SH and CHP 212 cells. Knockdown of miR-494-3p also suppressed neurotoxicity induced by MPP+ in SK-N-SH and CHP 212 cells. BDNF was validated as a target of miR-494-3p and its silence abated the suppressive effect of miR-494-3p on MPP+-induced neurotoxicity. Moreover, addition of miR-494-3p and silence of BDNF mitigated the effect of PPX on MPP+-induced neurotoxicity. PPX inhibited MPP+-induced neurotoxicity in SK-N-SH and CHP 212 cells by decreasing miR-494-3p and increasing BDNF, indicating the potential therapeutic effect of PPX on Parkinson's disease.

中文翻译：

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普拉克索通过miR-494-3p / BDNF抑制MPP +诱导的神经毒性。

普拉克索（PPX）是用于治疗帕金森氏病的常用药物。然而，该机制允许PPX在帕金森氏病进展中的作用仍然未知。这项研究旨在调查PPX在1-甲基-4-苯基吡啶鎓（MPP +）处理的神经母细胞瘤细胞中的作用，并探讨PPX与miR-494-3p /脑源性神经营养因子（BDNF）轴之间的相互作用。用MPP +攻击的SK-N-SH和CHP 212细胞用作帕金森氏病的细胞模型，并与PPX孵育。通过定量实时聚合酶链反应或western blot检测miR-494-3p和BDNF的表达水平。通过细胞凋亡，炎症反应和氧化应激研究了神经毒性。荧光素酶报道分子和RNA免疫沉淀法证实了miR-494-3p和BDNF之间的靶标关联。在MPP +处理的SK-N-SH和CHP 212细胞中，miR-494-3p表达增加，而BDNF水平降低，这可通过引入PPX来逆转。普拉克索减弱了MPP +处理的SK-N-SH和CHP 212细胞的细胞凋亡，炎症反应和氧化应激。敲低miR-494-3p还可抑制MPP +在SK-N-SH和CHP 212细胞中诱导的神经毒性。BDNF被证实是miR-494-3p的靶标，其沉默减弱了miR-494-3p对MPP +诱导的神经毒性的抑制作用。此外，添加miR-494-3p和BDNF沉默可减轻PPX对MPP +诱导的神经毒性的影响。