Small molecule specifically inhibiting microglial nitric oxide release could become a potential treatment for neuroinflammation
Authors
- P. Jordan
- A. Costa
- E. Specker
- O. Popp
- A. Volkamer
- R. Piske
- T. Obrusnik
- S. Kleissle
- K. Stuke
- A. Rex
- M. Neuenschwander
- J.P. von Kries
- M. Nazare
- P. Mertins
- H. Kettenmann
- S.A. Wolf
Journal
- PLoS ONE
Citation
- PLoS ONE 18 (2): e0278325
Abstract
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.