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

• Published in: Journal of clinical neuroscience Vol. 65; pp. 125 - 133
• Main Authors: Zeng, Rong, Luo, Di-Xian, Li, Hai-Peng, Zhang, Qi-Shan, Lei, Sheng-Suo, Chen, Ji-Hua
• Format: Journal Article
• Language: English
• Published: Scotland Elsevier Ltd 01.07.2019
• Subjects: Caspase-1; FoxO1; miRNA-135b; NLRP3; Parkinson’s disease; Pyroptosis; NLRP3; miRNA-135b; Pyroptosis; Parkinson’s disease; FoxO1; Caspase-1
• ISSN: 0967-5868; 1532-2653
• DOI: 10.1016/j.jocn.2019.04.004

•We provided the first evidence that miR-135b was downregulated while FoxO1 was inversely upregulated in MPP+-induced PD.•FoxO1 was verified as the direct downstream target of miR-135b in Parkinson's disease.•Overexpression of miR-135b suppressed the process of pyroptosis in SH-SY5Y and PC-12 cell lines.•Overexpression of FoxO1 reversed the downregulation of pyroptotic genes and LDH release induced by miR-135b mimics.•A pathway composed of miR-135b, FoxO1, TXNIP and NLRP3 axis that regulated SH-SY5Y and PC-12 cells pyroptosis in PD. 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.