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Pramipexole Inhibits MPP+-Induced Neurotoxicity by miR-494-3p/BDNF

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Abstract

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.

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  1. Chao Deng and Yong Xiang have contributed equally to this work.

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  1. Department of Neurology, Renmin Hospital, Hubei University of Medicine, 39 Chaoyang Road, Shiyan City, 442000, Hubei Province, China

    Chao Deng, Jianping Zhu, Junlan Yuan, Yong Xiang & Li Dai

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Deng, C., Zhu, J., Yuan, J. et al. Pramipexole Inhibits MPP+-Induced Neurotoxicity by miR-494-3p/BDNF. Neurochem Res 45, 268–277 (2020). https://doi.org/10.1007/s11064-019-02910-5

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