Upregulation of Cysteine Protease Cathepsin X in the 6-Hydroxydopamine Model of Parkinson’s Disease
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by loss of midbrain dopaminergic neurons in the substantia nigra pars compacta (SNc). In vitro, a contribution to neuroinflammation and neurotoxicity has been shown for the lysosomal protease cathepsin X; however, its expression...
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Frontiers Media S.A.
2018-11-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnmol.2018.00412/full |
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| author | Anja Pišlar Larisa Tratnjek Gordana Glavan Marko Živin Janko Kos Janko Kos |
| author_facet | Anja Pišlar Larisa Tratnjek Gordana Glavan Marko Živin Janko Kos Janko Kos |
| author_sort | Anja Pišlar |
| collection | DOAJ |
| description | Parkinson’s disease (PD) is a neurodegenerative disorder characterized by loss of midbrain dopaminergic neurons in the substantia nigra pars compacta (SNc). In vitro, a contribution to neuroinflammation and neurotoxicity has been shown for the lysosomal protease cathepsin X; however, its expression and its role in PD remain unknown. Therefore, the current study was designed to address the regional, cellular, and subcellular localization and activity of cathepsin X in hemi-parkinsonian rats with 6-hydroxydopamine (6-OHDA)-induced excitotoxicity in the unilateral medial forebrain bundle (MFB) lesion. We report for the first time that cathepsin X expression and activity are rapidly increased in the ipsilateral SNc after injection of 6-OHDA into the MFB reaching a maximum after 12 h but seem to stay strongly upregulated after 4 weeks after injection. At early time points of 6-OHDA injection into the MFB, the increased cathepsin X is localized in the lysosomes in the neuronal, predominantly tyrosine hydroxylase-positive dopaminergic cells. After 12 h of 6-OHDA induced lesion, only a few activated microglial cells are positive for cathepsin X whereas, in 4 weeks post-lesion accompanied with complete loss of dopaminergic neurons, there is persistent cathepsin X upregulation restricted to activated glia cells. Taken together, our results demonstrate that cathepsin X upregulation in the lesioned dopaminergic system may play a role as a pathogenic factor in PD. Moreover, inhibition of cathepsin X expression or activity may be useful in protecting the nigrostriatal dopaminergic projection in the PD. |
| first_indexed | 2024-12-21T12:09:31Z |
| format | Article |
| id | doaj.art-d58e8c3736d44f1e9bbcca9d106e2c8c |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-21T12:09:31Z |
| publishDate | 2018-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-d58e8c3736d44f1e9bbcca9d106e2c8c2022-12-21T19:04:37ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992018-11-011110.3389/fnmol.2018.00412331584Upregulation of Cysteine Protease Cathepsin X in the 6-Hydroxydopamine Model of Parkinson’s DiseaseAnja Pišlar0Larisa Tratnjek1Gordana Glavan2Marko Živin3Janko Kos4Janko Kos5Department of Pharmaceutical Biology, Faculty of Pharmacy, University of Ljubljana, Ljubljana, SloveniaInstitute of Pathophysiology, Medical Faculty, University of Ljubljana, Ljubljana, SloveniaDepartment of Biology, Biotechnical Faculty, University of Ljubljana, Ljubljana, SloveniaInstitute of Pathophysiology, Medical Faculty, University of Ljubljana, Ljubljana, SloveniaDepartment of Pharmaceutical Biology, Faculty of Pharmacy, University of Ljubljana, Ljubljana, SloveniaDepartment of Biotechnology, Jožef Stefan Institute, Ljubljana, SloveniaParkinson’s disease (PD) is a neurodegenerative disorder characterized by loss of midbrain dopaminergic neurons in the substantia nigra pars compacta (SNc). In vitro, a contribution to neuroinflammation and neurotoxicity has been shown for the lysosomal protease cathepsin X; however, its expression and its role in PD remain unknown. Therefore, the current study was designed to address the regional, cellular, and subcellular localization and activity of cathepsin X in hemi-parkinsonian rats with 6-hydroxydopamine (6-OHDA)-induced excitotoxicity in the unilateral medial forebrain bundle (MFB) lesion. We report for the first time that cathepsin X expression and activity are rapidly increased in the ipsilateral SNc after injection of 6-OHDA into the MFB reaching a maximum after 12 h but seem to stay strongly upregulated after 4 weeks after injection. At early time points of 6-OHDA injection into the MFB, the increased cathepsin X is localized in the lysosomes in the neuronal, predominantly tyrosine hydroxylase-positive dopaminergic cells. After 12 h of 6-OHDA induced lesion, only a few activated microglial cells are positive for cathepsin X whereas, in 4 weeks post-lesion accompanied with complete loss of dopaminergic neurons, there is persistent cathepsin X upregulation restricted to activated glia cells. Taken together, our results demonstrate that cathepsin X upregulation in the lesioned dopaminergic system may play a role as a pathogenic factor in PD. Moreover, inhibition of cathepsin X expression or activity may be useful in protecting the nigrostriatal dopaminergic projection in the PD.https://www.frontiersin.org/article/10.3389/fnmol.2018.00412/full6-hydroxydopaminecathepsin Xdopaminergic neuronsglial cellsneurodegenerationParkinson’s disease |
| spellingShingle | Anja Pišlar Larisa Tratnjek Gordana Glavan Marko Živin Janko Kos Janko Kos Upregulation of Cysteine Protease Cathepsin X in the 6-Hydroxydopamine Model of Parkinson’s Disease Frontiers in Molecular Neuroscience 6-hydroxydopamine cathepsin X dopaminergic neurons glial cells neurodegeneration Parkinson’s disease |
| title | Upregulation of Cysteine Protease Cathepsin X in the 6-Hydroxydopamine Model of Parkinson’s Disease |
| title_full | Upregulation of Cysteine Protease Cathepsin X in the 6-Hydroxydopamine Model of Parkinson’s Disease |
| title_fullStr | Upregulation of Cysteine Protease Cathepsin X in the 6-Hydroxydopamine Model of Parkinson’s Disease |
| title_full_unstemmed | Upregulation of Cysteine Protease Cathepsin X in the 6-Hydroxydopamine Model of Parkinson’s Disease |
| title_short | Upregulation of Cysteine Protease Cathepsin X in the 6-Hydroxydopamine Model of Parkinson’s Disease |
| title_sort | upregulation of cysteine protease cathepsin x in the 6 hydroxydopamine model of parkinson s disease |
| topic | 6-hydroxydopamine cathepsin X dopaminergic neurons glial cells neurodegeneration Parkinson’s disease |
| url | https://www.frontiersin.org/article/10.3389/fnmol.2018.00412/full |
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