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

Autor: Jordan, P., Costa, A., Specker, E., Popp, O., Volkamer, A., Piske, R., Obrusnik, T., Kleissle, S., Stuke, K., Rex, A., Neuenschwander, M., von Kries, J.P., Nazare, M., Mertins, P., Kettenmann, H., Wolf, S.A.
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Popis: 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.
Databáze: OpenAIRE