Neuroprotective effects of coenzyme Q10 in Parkinson's model via a novel Q10/miR-149-5p/MMPs pathway.

Parkinson's disease (PD) is a complex neurodegenerative disease in which the understanding of the underlying molecular mechanisms can be constructive in the diagnosis and treatment. Matrix metalloproteinase (MMPs) elevation and damage to the blood–brain barrier (BBB) are critical mechanisms involved in the PD separation. Studies have revealed that changes in miR-149-5p and CoQ10 are associated with BBB damage, and CoQ10 can affect the levels of some miRs. Hence, in the present study, we aimed to evaluate CoQ10 and miR-149-5p mimic on miR-149-5p, MMPs and TH expression, and behavioral functions of the PD models. PD was induced by injection of 6-OHDA into the rats' Medial Forbrain Bundle (MFB). The behavioral tests, including the Rotation test, Rotarod test, and Open field test, have been directed two weeks after PD induction. Next, the MiR-149-5p mimic (miR-mimic) and CoQ10 have been administered to rats. The same behavioral tests have been evaluated two weeks after administration to investigate the effect of miR-149-5p mimic and CoQ10. The rats were followed extra four weeks, and the behavioral tests have performed again. Finally, the expression of MMPs and miR-149-5p genes was measured using RT-qPCR, and tyrosine hydroxylase (TH) was assessed through immunohistochemistry analysis. According to the obtained results, the level of miR-149-5p has decreased, followed by PD induction in rats. RT-qPCR analysis has represented upregulation and downregulation of miR-149-5p and MMP-2,9, respectively, after miR-mimic and CoQ10 treatment. The treated rats have also represented improved motor function and increased TH +  cells in the striatum according to the behavioral tests and immunohistochemistry assay. Taking together miR-149 and CoQ10 has shown to have an impressive potential to prevent damage to dopaminergic neurons caused by 6-OHDA injection through reducing MMP-2,9, increased TH expression, and improved motor function.