MicroRNA-135b alleviates MPP+-mediated Parkinson's disease in in vitro model through suppressing FoxO1-induced NLRP3 inflammasome and pyroptosis.

The present study focused on the novel roles and the underlying mechanisms of miR-135b in pyroptosis of MPP+-induced Parkinson's disease (PD). We established an in vitro PD model induced by MPP+. Our results demonstrated miR-135b was lower while FoxO1 was inversely higher in MPP+-treated SH-SY5Y and PC-12 cells. Luciferase reporter assay showed FoxO1 was a downstream target of miR-135b. MiR-135b mimics suppressed MPP+-induced pyroptosis and the upregulation of TXNIP, NLRP3, Caspase-1, ASC, GSDMDNterm and IL-1β. Moreover, FoxO1 overexpression had no effect on miR-135b but reversed its own downregulation caused by miR-135b mimics. Meanwhile, overexpression of FoxO1 abolished the inhibitory effects of miR-135b on pyroptosis and reversed the downregulation of pyroptotic genes and LDH release. In summary, miR-135b played a protective role in Parkinson's disease via inhibiting pyroptosis by targeting FoxO1. MiR-135b might serve as a potential therapeutic target in the treatment of Parkinson's disease.