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| Item Type: | Article |
|---|---|
| Title: | Small molecule specifically inhibiting microglial nitric oxide release could become a potential treatment for neuroinflammation |
| Creators: |
Jordan, P., Costa, A., Specker, E.  ORCID: https://orcid.org/0000-0002-9471-9520, Popp, O. ORCID: https://orcid.org/0000-0001-6240-4666, Volkamer, A. ORCID: https://orcid.org/0000-0002-3760-580X, Piske, R., Obrusnik, T., Kleissle, S., Stuke, K., Rex, A. ORCID: https://orcid.org/0000-0003-3924-956X, Neuenschwander, M. ORCID: https://orcid.org/0000-0002-3114-7975, von Kries, J.P. ORCID: https://orcid.org/0000-0003-4716-4988, Nazare, M. ORCID: https://orcid.org/0000-0002-1602-2330, Mertins, P. ORCID: https://orcid.org/0000-0002-2245-528X, Kettenmann, H. ORCID: https://orcid.org/0000-0001-8208-0291 and Wolf, S.A. ORCID: https://orcid.org/0000-0003-0922-8418
|
| 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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