학술논문
Small molecule inhibiting microglial nitric oxide release could become a potential treatment for neuroinflammation.
Document Type
Article
Author
Source
Subject
*SMALL molecules
*NITRIC oxide
*NITRIC-oxide synthases
*MASS spectrometry
*MICROGLIA
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Language
ISSN
1932-6203
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. [ABSTRACT FROM AUTHOR]