MiR-29a inhibits MPP + - Induced cell death and inflammation in Parkinson's disease model in vitro by potential targeting of MAVS

Eur J Pharmacol. 2022 Nov 5:934:175302. doi: 10.1016/j.ejphar.2022.175302. Epub 2022 Sep 26.

Abstract

Parkinson's disease (PD) primarily affects the motor system and is the second most common age-related neurodegenerative disorder after Alzheimer's disease. Mitochondrial complex I deficiency and functional abnormalities are implicated in the development of PD. MicroRNA-29a (miR-29a) has emerged as a critical miRNA in PD. This study aims to investigate the protective role of miR-29a in MPP+ in SH-SY5Y cell lines in vitro PD model by targeting mitochondrial antiviral signaling protein (MAVS). Administration of MPP + inhibited miR-29a expression in SH-SY5Y cell lines. Our findings prove that miR-29a mimic treatment decreased cell death, ROS production, MAVS, p-IRF3, p-NFκBp65, IL-6, cleaved caspase-3, cleaved-PARP, LC3BII, and death while increasing glutathione peroxidase 1 and manganese superoxide dismutase after MPP + treatment in SH-SY5Y cells. Furthermore, MAVS expression was significantly corrected with the above genes in our in vitro model of PD. Luciferase activity analysis also confirmed that miR-29a specific binding 3'UTR of MAVS repressed expression. In conclusion, this research provides novel insight into a neuroprotective pathway of miR-29a and could thus serve as a possible therapeutic target for improving the treatment of PD.

Keywords: Cellular death; Inflammation; MAVS; MicroRNA-29a; Parkinson's disease.

MeSH terms

  • 1-Methyl-4-phenylpyridinium
  • 3' Untranslated Regions
  • Antiviral Agents / pharmacology
  • Apoptosis / genetics
  • Caspase 3 / genetics
  • Cell Death
  • Cell Line, Tumor
  • Humans
  • Inflammation / genetics
  • Interleukin-6 / genetics
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Neuroblastoma* / genetics
  • Parkinson Disease* / genetics
  • Parkinson Disease* / metabolism
  • Poly(ADP-ribose) Polymerase Inhibitors / pharmacology
  • Reactive Oxygen Species / metabolism
  • Superoxide Dismutase / metabolism

Substances

  • 1-Methyl-4-phenylpyridinium
  • Caspase 3
  • Reactive Oxygen Species
  • 3' Untranslated Regions
  • Interleukin-6
  • Poly(ADP-ribose) Polymerase Inhibitors
  • MicroRNAs
  • Superoxide Dismutase
  • Antiviral Agents