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

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 li...

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Detalles Bibliográficos
Autores principales: Jordan, Philipp, Costa, Amanda, Specker, Edgar, Popp, Oliver, Volkamer, Andrea, Piske, Regina, Obrusnik, Tessa, Kleissle, Sabrina, Stuke, Kevin, Rex, Andre, Neuenschwander, Martin, von Kries, Jens Peter, Nazare, Marc, Mertins, Phillip, Kettenmann, Helmut, Wolf, Susanne A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9901772/
https://www.ncbi.nlm.nih.gov/pubmed/36745631
http://dx.doi.org/10.1371/journal.pone.0278325
Descripción
Sumario: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 IC(50) (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.

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