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

Background: 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.

Methods: 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.

Results: 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.

Conclusion: PPX mitigated neuronal injury in MPP⁺-induced cells and MPTP-induced mice by activating BNIP3-mediated Mitophagy via directly decreasing miR-96.