Small molecule inhibiting microglial nitric oxide release could become a potential treatment for neuroinflammation.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2023
2023
Historique:
received:
28
12
2021
accepted:
14
11
2022
entrez:
6
2
2023
pubmed:
7
2
2023
medline:
9
2
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 36745631
doi: 10.1371/journal.pone.0278325
pii: PONE-D-21-40798
pmc: PMC9901772
doi:
Substances chimiques
Nitric Oxide
31C4KY9ESH
Nitric Oxide Synthase Type II
EC 1.14.13.39
Lipopolysaccharides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0278325Informations de copyright
Copyright: © 2023 Jordan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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