当前位置： SCI文献检索 > EXPERIMENTAL AND MOLECULAR PATHOLOGY期刊下所有文献 > MiR-410 exerts neuroprotective effects in a cellular model of Parkinson's disease induced by 6-hydroxydopamine via inhibiting the PTEN/AKT/mTOR signaling pathway.

MiR-410 exerts neuroprotective effects in a cellular model of Parkinson's disease induced by 6-hydroxydopamine via inhibiting the PTEN/AKT/mTOR signaling pathway.

Abstract：

:Parkinson's disease (PD) is a chronic neurodegenerative disease characterized by loss of dopaminergic neurons in the substantia nigra. Recently, microRNAs (miRNAs) were emerging as important mediators in dopaminergic neuron biology. This study determined miR-410 expression in the 6-hydroxydopamine (6-OHDA)-induced in vitro cellular model of PD and explored the mechanistic role of miR-410 in the modulation of neuronal cell viability and apoptosis. Our data showed that 6-OHDA concentration-dependently suppressed neuronal cell viability and miR-410 expression in SH-SY5Y and PC12 cells. Overexpression of miR-410 partially restored the effects of 6-OHDA on neuronal cell viability, apoptosis, capsase-3 activity as well as reactive oxygen species (ROS) production. On the other hand, inhibition of miR-410 decreased neuronal cell viability and increased apoptotic rates, capase-3 activity as well as ROS production. Furthermore, the potential targets of miR-410 were predicted by TargetScan tool, and we verified that phosphatase and tensin homolog (PTEN) was a target of miR-410 as confirmed by the dual-luciferase reporter assay. MiR-410 overexpression attenuated PTEN expression and mediated the effects in the 6-OHDA-treated cells via targeting PTEN in SH-SY5Y and PC12 cells. Furthermore, 6-OHDA treatment suppressed the protein expression of phosphorylated AKT and phosphorylated mTOR, which was partially attenuated by miR-410 overexpression in SH-SY5Y and PC12 cells. MiR-410 overexpression increased phosphorylated AKT and phosphorylated mTOR protein expression, and this effect was attenuated by PTEN overexpression in both SH-SY5Y and PC12 cells. Collectively, this is the first study to demonstrate the neuroprotective effects of miR-410 in a 6-OHDA-induced cellular model of PD, and our data implied that miR-410 exerted its neuroprotective effects via regulating PTEN/AKT/mTOR signaling axis. The present study may suggest new paradigm to study the pathology of PD.

journal_name

Exp Mol Pathol

journal_title

Experimental and molecular pathology

authors

Ge H,Yan Z,Zhu H,Zhao H

doi

10.1016/j.yexmp.2019.05.002

subject

Has Abstract

pub_date

2019-08-01 00:00:00

pages

16-24

eissn

0014-4800

issn

1096-0945

pii

S0014-4800(19)30166-2

journal_volume

109

pub_type

杂志文章

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