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Inhibition of cathepsin X reduces the strength of microglial-mediated neuroinflammationPišlar, Anja ...Inflammation plays a central role in the processes associated with neurodegeneration. The inflammatory response is mediated by activated microglia that release inflammatory mediators to the neuronal ... environment. Microglia-derived lysosomal cathepsins, including cathepsin X, are increasingly recognized as important mediators of the inflammation involved in lipopolysaccharide (LPS)-induced neuroinflammation. The current study was undertaken to investigate the role of cathepsin X and its molecular target, gamma-enolase, in neuroinflammation and to elucidate the underlying mechanism. We determined that the exposure of activated BV2 and EOC 13.31 cells to LPS led to increased levels of cathepsin X protein and activity in the culture supernatants in a concentration- and time-dependent manner. In contrast, LPS stimulation of these two cells reduced the release of active gamma-enolase in a manner regulated by the cathepsin X activity. Cathepsin X inhibitor AMS36 significantly reduced LPS-induced production of nitric oxide, reactive oxygen species and the pro-inflammatory cytokines interleukin-6 and tumor necrosis factor- alpha from BV2 cells. Inhibition of cathepsin X suppressed microglial activation through the reduced caspase-3 activity, together with diminished microglial cell death and apoptosis, and also through inhibition of the activity of the mitogen-activated protein kinases. Further, SH-SY5Y treatment with culture supernatants of activated microglial cells showed that cathepsin X inhibition reduces microglia-mediated neurotoxicity. These results indicate that up-regulated expression and increased release and activity of microglial cathepsin X leads to microglia activation-mediated neurodegeneration. Cathepsin X inhibitor caused neuroprotection via its inhibition of the activation of microglia. Cathepsin X could thus be a potential therapeutic target for neuroinflammatory disorders.Source: Neuropharmacology. - ISSN 0028-3908 (Vol. 114, 2017, str. 88-100)Type of material - article, component partPublish date - 2017Language - englishCOBISS.SI-ID - 4249201
Author
Pišlar, Anja |
Božić, Biljana |
Zidar, Nace |
Kos, Janko, 1959-
Topics
cathepsin X |
gamma-enolase |
microglia |
neuroinflammation |
neuroprotection
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Database name | Field | Year |
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Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
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Pišlar, Anja | 32035 |
Božić, Biljana | |
Zidar, Nace | 28905 |
Kos, Janko, 1959- | 04648 |
Source: Personal bibliographies
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