20.500.12556/RUL-145022 Neuroinflammation-induced upregulation of glial cathepsin X expression and activity in vivo Neuroinflammation is an important factor in pathogenesis of neurodegenerative diseases. Microglia-derived lysosomal cathepsins have been increasingly recognized as important inflammatory mediators that trigger signalling pathways that aggravate neuroinflammation. In vitro, a contribution to neuroinflammation processes has been shown for cathepsin X, however; the expression patterns and functional roles of cathepsin X in neuroinflammatory brain pathology remain elusive. In this study, we analyzed the expression, activity, regional distribution and cellular localization of cathepsin X in the rat brain with neuroinflammation-induced neurodegeneration. Unilateral injection of LPS induced strong upregulation of cathepsin X expression and its activity in the ipsilateral striatum. In addition to the striatum, cathepsin X overexpression was detected in other brain areas such as cerebral cortex, corpus callosum, subventricular zone and external globus pallidus, whereas the upregulation was mainly restricted to activated microglia and reactive astrocytes. Continuous administration of the cathepsin X inhibitor AMS36 indicated protective effects against LPS-induced striatal degeneration, as seen by the attenuated the LPS-mediated dilation of the lateral ventricles and partial decreased extent of striatal lesion. Taken together, our results indicate that cathepsin X plays a role as a pathogenic factor in neuroinflammation-induced neurodegeneration and represents a potential therapeutic target for neurodegenerative diseases associated with neuroinflammation. neuroinflammation neurodegeneration lipopolysaccharide glia cathepsin X neuroprotection živčno vnetje katepsin X nevrodegenerativne bolezni degenerativne bolezni true false true Angleški jezik Slovenski jezik Članek v reviji 2023-03-30 10:27:19 2023-03-30 10:27:23 2023-03-31 03:36:29 0000-00-00 00:00:00 2020 0 0 17 str. Vol. 13, art. 575453 2020 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616.831-003.8+616-003.8 1662-5099 10.3389/fnmol.2020.575453 36086275 fnmol-13-575453_(2).pdf fnmol-13-575453_(2).pdf 1 12285C1A8AFD4CE48DFF83C73AB8D5E4 2ffc352eb334d32c5047cec86552024f910bbdd7cb543df6d749aa60b30a66c8 6663286b-ced9-11ed-a314-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=167643 https://www.frontiersin.org/articles/10.3389/fnmol.2020.575453/full 0 98090ea4-ced4-11ed-a314-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=167641 Fakulteta za farmacijo Medicinska fakulteta Biotehniška fakulteta 0 0 0