Activators of alpha synuclein expression identified by reporter cell line-based high throughput drug screen

Sci Rep. 2021 Oct 6;11(1):19857. doi: 10.1038/s41598-021-98841-9.

Abstract

Multiplications, mutations and dysregulation of the alpha synuclein gene (SNCA) are associated with the demise of dopaminergic neurons and are considered to play important roles in the pathogenesis of familial and sporadic forms of Parkinson's disease. Regulation of SNCA expression might thus be an appropriate target for treatment. We aimed to identify specific modulators of SNCA transcription, generated CRISPR/Cas9 modified SNCA-GFP-luciferase (LUC) genomic fusion- and control cell lines and screened a library of 1649 bioactive compounds, including the FDA approved drugs. We found no inhibitors but three selective activators which increased SNCA mRNA and protein levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • DNA Methylation
  • Drug Discovery* / methods
  • Gene Expression
  • Gene Expression Regulation / drug effects*
  • Genes, Reporter
  • High-Throughput Screening Assays*
  • Histones / metabolism
  • Humans
  • Small Molecule Libraries
  • alpha-Synuclein / genetics*
  • alpha-Synuclein / metabolism

Substances

  • Histones
  • SNCA protein, human
  • Small Molecule Libraries
  • alpha-Synuclein