Neuroinflammation-induced upregulation of glial cathepsin X expression and activity in vivo

Pišlar, Anja (author), Tratnjek, Larisa (author), Glavan, Gordana (author), Zidar, Nace (author), Živin, Marko (author), Kos, Janko (author)

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.

• Language: English
• Keywords: neuroinflammation, neurodegeneration, lipopolysaccharide, glia, cathepsin X, neuroprotection
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy; MF - Faculty of Medicine; BF - Biotechnical Faculty
• Publication status: Published
• Publication version: Version of Record
• Year: 2020
• Number of pages: 17 str.
• Numbering: Vol. 13, art. 575453
• PID: 20.500.12556/RUL-145022
• UDC: 616.831-003.8+616-003.8
• ISSN on article: 1662-5099
• DOI: 10.3389/fnmol.2020.575453
• COBISS.SI-ID: 36086275
• Publication date in RUL: 30.03.2023

Record is a part of a journal

• Title: Frontiers in molecular neuroscience
• Shortened title: Front. mol. neurosci.
• Publisher: Frontiers Media
• ISSN: 1662-5099
• COBISS.SI-ID: 5029402

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: živčno vnetje, katepsin X, nevrodegenerativne bolezni, degenerativne bolezni