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

J Clin Neurosci. 2019 Jul:65:125-133. doi: 10.1016/j.jocn.2019.04.004. Epub 2019 Apr 26.

Abstract

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.

Keywords: Caspase-1; FoxO1; NLRP3; Parkinson’s disease; Pyroptosis; miRNA-135b.

MeSH terms

  • Carrier Proteins / metabolism
  • Forkhead Box Protein O1 / metabolism*
  • Humans
  • Inflammasomes / metabolism*
  • Intracellular Signaling Peptides and Proteins
  • MicroRNAs / genetics*
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Neoplasm Proteins / genetics
  • Parkinson Disease / genetics*
  • Phosphate-Binding Proteins
  • Pyroptosis / genetics*
  • Up-Regulation

Substances

  • Carrier Proteins
  • FOXO1 protein, human
  • Forkhead Box Protein O1
  • GSDMD protein, human
  • Inflammasomes
  • Intracellular Signaling Peptides and Proteins
  • MIRN135 microRNA, human
  • MicroRNAs
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • Neoplasm Proteins
  • Phosphate-Binding Proteins
  • TXNIP protein, human