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Item Type: | Article |
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Title: | Small molecule specifically inhibiting microglial nitric oxide release could become a potential treatment for neuroinflammation |
Creators Name: | Jordan, P. and Costa, A. and Specker, E. and Popp, O. and Volkamer, A. and Piske, R. and Obrusnik, T. and Kleissle, S. and Stuke, K. and Rex, A. and Neuenschwander, M. and von Kries, J.P. and Nazare, M. and Mertins, P. and 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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