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Inhibition of Cathepsin S Produces Neuroprotective Effects after Traumatic Brain Injury in Mice
Cathepsin S (CatS) is a cysteine protease normally present in lysosomes. It has long been regarded as an enzyme that is primarily involved in general protein degradation. More recently, mounting evidence has shown that it is involved in Alzheimer disease, seizures, age-related inflammatory processes...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3824312/ https://www.ncbi.nlm.nih.gov/pubmed/24282339 http://dx.doi.org/10.1155/2013/187873 |
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author | Xu, Jianguo Wang, Handong Ding, Ke Lu, Xinyu Li, Tao Wang, Jiawei Wang, Chunxi Wang, Jian |
author_facet | Xu, Jianguo Wang, Handong Ding, Ke Lu, Xinyu Li, Tao Wang, Jiawei Wang, Chunxi Wang, Jian |
author_sort | Xu, Jianguo |
collection | PubMed |
description | Cathepsin S (CatS) is a cysteine protease normally present in lysosomes. It has long been regarded as an enzyme that is primarily involved in general protein degradation. More recently, mounting evidence has shown that it is involved in Alzheimer disease, seizures, age-related inflammatory processes, and neuropathic pain. In this study, we investigated the time course of CatS protein and mRNA expression and the cellular distribution of CatS in a mouse model of traumatic brain injury (TBI). To clarify the roles of CatS in TBI, we injected the mice intraventricularly with LHVS, a nonbrain penetrant, irreversible CatS inhibitor, and examined the effect on inflammation and neurobehavioral function. We found that expression of CatS was increased as early as 1 h after TBI at both protein and mRNA levels. The increased expression was detected in microglia and neurons. Inhibition of CatS significantly reduced the level of TBI-induced inflammatory factors in brain tissue and alleviated brain edema. Additionally, administration of LHVS led to a decrease in neuronal degeneration and improved neurobehavioral function. These results imply that CatS is involved in the secondary injury after TBI and provide a new perspective for preventing secondary injury after TBI. |
format | Online Article Text |
id | pubmed-3824312 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-38243122013-11-26 Inhibition of Cathepsin S Produces Neuroprotective Effects after Traumatic Brain Injury in Mice Xu, Jianguo Wang, Handong Ding, Ke Lu, Xinyu Li, Tao Wang, Jiawei Wang, Chunxi Wang, Jian Mediators Inflamm Research Article Cathepsin S (CatS) is a cysteine protease normally present in lysosomes. It has long been regarded as an enzyme that is primarily involved in general protein degradation. More recently, mounting evidence has shown that it is involved in Alzheimer disease, seizures, age-related inflammatory processes, and neuropathic pain. In this study, we investigated the time course of CatS protein and mRNA expression and the cellular distribution of CatS in a mouse model of traumatic brain injury (TBI). To clarify the roles of CatS in TBI, we injected the mice intraventricularly with LHVS, a nonbrain penetrant, irreversible CatS inhibitor, and examined the effect on inflammation and neurobehavioral function. We found that expression of CatS was increased as early as 1 h after TBI at both protein and mRNA levels. The increased expression was detected in microglia and neurons. Inhibition of CatS significantly reduced the level of TBI-induced inflammatory factors in brain tissue and alleviated brain edema. Additionally, administration of LHVS led to a decrease in neuronal degeneration and improved neurobehavioral function. These results imply that CatS is involved in the secondary injury after TBI and provide a new perspective for preventing secondary injury after TBI. Hindawi Publishing Corporation 2013 2013-10-24 /pmc/articles/PMC3824312/ /pubmed/24282339 http://dx.doi.org/10.1155/2013/187873 Text en Copyright © 2013 Jianguo Xu et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Xu, Jianguo Wang, Handong Ding, Ke Lu, Xinyu Li, Tao Wang, Jiawei Wang, Chunxi Wang, Jian Inhibition of Cathepsin S Produces Neuroprotective Effects after Traumatic Brain Injury in Mice |
title | Inhibition of Cathepsin S Produces Neuroprotective Effects after Traumatic Brain Injury in Mice |
title_full | Inhibition of Cathepsin S Produces Neuroprotective Effects after Traumatic Brain Injury in Mice |
title_fullStr | Inhibition of Cathepsin S Produces Neuroprotective Effects after Traumatic Brain Injury in Mice |
title_full_unstemmed | Inhibition of Cathepsin S Produces Neuroprotective Effects after Traumatic Brain Injury in Mice |
title_short | Inhibition of Cathepsin S Produces Neuroprotective Effects after Traumatic Brain Injury in Mice |
title_sort | inhibition of cathepsin s produces neuroprotective effects after traumatic brain injury in mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3824312/ https://www.ncbi.nlm.nih.gov/pubmed/24282339 http://dx.doi.org/10.1155/2013/187873 |
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