Inhibition of miR-937-3p by targeting SNCB ameliorates rotenone-induced toxicity in SH- SY5Y cells by reducing alpha-synuclein aggregation and apoptosis

Parkinson’s disease (PD) is a prevalent neurodegenerative disorder marked by dopaminergic neuronal loss in the substantia nigra and the presence of Lewy bodies formed by alpha-synuclein (α-syn) aggregation. This study was performed to determine whether miR-937-3p inhibited α-syn aggregation and apoptosis in a rotenone (ROT)-induced PD cell model. We examined miR-937-3p target genes through GO analysis, luciferase assay, and RT-qPCR and revealed the expression levels of apoptosis or PD-related proteins via Western blotting analysis. Afterward, we chose SCNB (Synuclein Beta; β-synuclein) as a target gene and confirmed its downregulation by miR-937-3p directly at a cellular level. With the miR-937-3p inhibitor (miR-937-3p-I), cell death was reduced, thereby increasing anti-apoptotic proteins (Bcl-2, Mcl-1, and pro-Caspase-3/-7/-9) and decreasing pro-apoptotic protein (Bax and cleaved-Caspase3) compared with those in the ROT group. The phosphorylated serine 129 (p-S129) α-syn (p-α-syn) decreased in Triton X-100-soluble fraction while increased in Triton X-100-insoluble fraction during ROT exposure. The miR-937-3p-I treatment reverted the ROT-induced toxicity on p-α-syn to clear the oligomeric α-syn. Neuronal markers, NeuN, MAP2, TUBB/Tuj1, NEFL, NEFM, and NFH/NEFH were increased in treatment with miR-937-3p-I compared with those in ROT. Our findings suggested that targeting miR-937-3p might be an effective treatment strategy for PD by promoting SNCB overexpression and reducing apoptosis.