Pramipexole attenuates neuronal injury in Parkinson's disease by targeting miR-96 to activate BNIP3-mediated mitophagy

Parkinson's disease is a common neurodegenerative problem. Pramipexole (PPX) plays protective role in Parkinson's disease. Nevertheless, the mechanism of PPX in Parkinson's disease-like neuronal injury is largely uncertain. 1-methyl-4-phenylpyridinium (MPP+)-stimulated neuronal cells and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice were used as the model of Parkinson's disease. MPP+-induced neuronal injury was assessed via cell viability, lactic dehydrogenase (LDH) release and apoptosis. microRNA-96 (miR-96) and BCL2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) abundances were examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) or Western blotting. Mitophagy was tested by Western blotting and immunofluorescence staining. MPTP-induced neuronal injury in mice was investigated via behavioral tests and TUNEL. PPX alleviated MPP+-induced neuronal injury via increasing cell viability and decreasing LDH release and apoptosis. PPX reversed MPP+-induced miR-96 expression and inhibition of mitophagy. miR-96 overexpression or BNIP3 interference weakened the suppressive role of PPX in MPP+-induced neuronal injury. miR-96 targeted BNIP3 to inhibit PTEN-induced putative kinase 1 (PINK1)/Parkin signals-mediated mitophagy. miR-96 overexpression promoted MPP+-induced neuronal injury via decreasing BNIP3. PPX weakened MPTP-induced neuronal injury in mice via regulating miR-96/BNIP3-mediated mitophagy. PPX mitigated neuronal injury in MPP+-induced cells and MPTP-induced mice by activating BNIP3-mediated mitophagy via directly decreasing miR-96. •PPX weakens MPP+-caused neuronal injury and apoptosis.•PPX suppresses miR-96 and activates BNIP3-mediated mitophagy.•miR-96 weakens the influence of PPX on MPP+-caused neuronal damage.•miR-96 targets BNIP3 to inhibit PINK1/Parkin signals-mediated mitophagy.•PPX mitigates MPTP-induced neuronal injury in mice by miR-96/BNIP3 axis.