PLoS ONE (Jan 2023)

Small molecule inhibiting microglial nitric oxide release could become a potential treatment for neuroinflammation.

  • Philipp Jordan,
  • Amanda Costa,
  • Edgar Specker,
  • Oliver Popp,
  • Andrea Volkamer,
  • Regina Piske,
  • Tessa Obrusnik,
  • Sabrina Kleissle,
  • Kevin Stuke,
  • Andre Rex,
  • Martin Neuenschwander,
  • Jens Peter von Kries,
  • Marc Nazare,
  • Phillip Mertins,
  • Helmut Kettenmann,
  • Susanne A Wolf

DOI
https://doi.org/10.1371/journal.pone.0278325
Journal volume & issue
Vol. 18, no. 2
p. e0278325

Abstract

Read online

Microglia are the immune effector cells of the central nervous system (CNS) and react to pathologic events with a complex process including the release of nitric oxide (NO). NO is a free radical, which is toxic for all cells at high concentrations. To target an exaggerated NO release, we tested a library of 16 544 chemical compounds for their effect on lipopolysaccharide (LPS)-induced NO release in cell line and primary neonatal microglia. We identified a compound (C1) which significantly reduced NO release in a dose-dependent manner, with a low IC50 (252 nM) and no toxic side effects in vitro or in vivo. Target finding strategies such as in silico modelling and mass spectroscopy hint towards a direct interaction between C1 and the nitric oxide synthase making C1 a great candidate for specific intra-cellular interaction with the NO producing machinery.