MicroRNA-599 regulates the development of Parkinson’s disease through mediating LRRK2 expression

OBJECTIVE: This study investigates whether microRNA-599 can inhibit the progression of Parkinson's disease (PD) by regulating the LRRK2 expression. We aim to search for a new therapeutic target for PD.

MATERIALS AND METHODS: A mouse model of PD was first established. A relative amount of TH+ neurons in the mouse brain was quantified by immunohistochemistry. The expression levels of microRNA-599 and LRRK2 in mouse brain tissues were determined by the quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot. Cell model of PD was constructed by MPP+ treatment in SH-SY5Y cells. The expression levels of microRNA-599 and LRRK2 in MPP+-induced SH-SY5Y cells were examined as well. We verified the binding condition between microRNA-599 and LRRK2 through dual-luciferase reporter gene assay. The viability and apoptosis in MPP+-induced SH-SY5Y cells overexpressing microRNA-599 were determined by cell counting kit-8 (CCK-8) assay and flow cytometry, respectively.

RESULTS: Compared with normal mice, TH+ neurons were fewer in the brain tissue of PD mice. MicroRNA-599 expression was lower, while LRRK2 expression was higher in brain tissues of PD mice relative to controls. Meanwhile, in vitro expression of microRNA-599 was downregulated and LRRK2 expression was upregulated in MPP+-induced SH-SY5Y cells. Dual-luciferase reporter gene assay verified the binding condition between microRNA-599 and LRRK2. The microRNA-599 overexpression downregulated the LRRK2 expression in SH-SY5Y cells, and conversely, the microRNA-599 knockdown upregulated the LRRK2 expression. Of note, the microRNA-599 overexpression protected MPP+-induced viability decrease and apoptosis acceleration in SH-SY5Y cells.

CONCLUSIONS: MicroRNA-599 is lowly expressed in both in vivo and in vitro PD model. MicroRNA-599 inhibits the development of PD through regulating the LRRK2 expression.

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