Upregulation of mir-132 induces dopaminergic neuronal death via activating SIRT1/P53 pathway

Neurosci Lett. 2021 Jan 1:740:135465. doi: 10.1016/j.neulet.2020.135465. Epub 2020 Nov 6.

Abstract

For several neurodegenerative disorders, including Parkinson's Disease (PD) and Alzheimer's Disease (AD), microRNAs (miRNAs) have been known to play a crucial role. So, in this study miR-132 and its role in PD cell models was investigated. We wanted to investigate the survival or death pathway involved in PD. We observed the expression levels of miR-132 in MPP+ - treated SH-SY5Y cell line, which acted as a PD cell model, and found an increased expression of miR-132. Moreover, through the Dual-Luciferase® Reporter (DLR™) Assay, it was also revealed that miR-132 targets SIRT1 3'UTR, a histone deacetylase, and decreases its activity, which results in increased acetylation of p53, an apoptotic inducer. p53 acetylation leads to overexpression of other pro-apoptotic genes like Puma and Noxa, which eventually leads to cell death. Here, we show that the upregulation of miR-132 in SH-SY5Y cells can induce apoptosis through the SIRT1/p53 pathway.

Keywords: Apoptosis; Parkinson’s disease (PD); SIRT1 suppression; miR132 upregulation; α-synuclein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / biosynthesis
  • Apoptosis Regulatory Proteins / genetics
  • Cell Death / physiology*
  • Cell Line
  • Cell Survival / genetics
  • Dopaminergic Neurons / physiology*
  • Genes, p53 / genetics
  • Genes, p53 / physiology*
  • Humans
  • Mice
  • Mice, Transgenic
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Parkinson Disease, Secondary / chemically induced
  • Parkinson Disease, Secondary / genetics
  • Signal Transduction / genetics
  • Signal Transduction / physiology*
  • Sirtuin 1 / genetics
  • Sirtuin 1 / physiology*

Substances

  • Apoptosis Regulatory Proteins
  • MIRN132 microRNA, human
  • MicroRNAs
  • SIRT1 protein, human
  • Sirtuin 1