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

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.

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

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Item Type:	Article
Title:	Small molecule specifically inhibiting microglial nitric oxide release could become a potential treatment for neuroinflammation
Creators Name:	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. and Wolf, S.A.
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.
Keywords:	Cell Line, Lipopolysaccharides, Microglia, Neuroinflammatory Diseases, Nitric Oxide Synthase Type II, Nitric Oxide
Source:	PLoS ONE
ISSN:	1932-6203
Publisher:	Public Library of Science
Volume:	18
Number:	2
Page Range:	e0278325
Date:	6 February 2023
Official Publication:	https://doi.org/10.1371/journal.pone.0278325
PubMed:	View item in PubMed

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