Genetic Deletion of Thorase Causes Purkinje Cell Loss and Impaired Motor Coordination Behavior
Thorase belongs to the AAA+ ATPase family, which plays a critical role in maintaining cellular homeostasis. Our previous work reported that Thorase was highly expressed in brain tissue, especially in the cerebellum. However, the roles of Thorase in the cerebellum have still not been characterized. I...
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2023-08-01
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| author | Chao Li Han Zhang Kexin Tong Menghua Cai Fei Gao Jia Yang Yi Xu Huaishan Wang Hui Chen Yu Hu Wei He Jianmin Zhang |
| author_facet | Chao Li Han Zhang Kexin Tong Menghua Cai Fei Gao Jia Yang Yi Xu Huaishan Wang Hui Chen Yu Hu Wei He Jianmin Zhang |
| author_sort | Chao Li |
| collection | DOAJ |
| description | Thorase belongs to the AAA+ ATPase family, which plays a critical role in maintaining cellular homeostasis. Our previous work reported that Thorase was highly expressed in brain tissue, especially in the cerebellum. However, the roles of Thorase in the cerebellum have still not been characterized. In this study, we generated conditional knockout mice (cKO) with Thorase deletion in Purkinje cells. Thorase cKO mice exhibited cerebellar degenerative diseases-like behavior and significant impairment in motor coordination. Thorase deletion resulted in more Purkinje neuron apoptosis, leading to Purkinje cell loss in the cerebellum of Thorase cKO mice. We also found enhanced expression of the inflammatory protein ASC, IL-1β, IL-6 and TNF-α in the Thorase cKO cerebellum, which contributed to the pathogenesis of cerebellar degenerative disease. Our findings provide a better understanding of the role of Thorase in the cerebellum, which is a theoretical basis for Thorase as a therapeutic drug target for neurodegenerative diseases. |
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| spelling | doaj.art-3b8a4429fc3742b19da82082073902cc2023-11-19T00:36:23ZengMDPI AGCells2073-44092023-08-011216203210.3390/cells12162032Genetic Deletion of Thorase Causes Purkinje Cell Loss and Impaired Motor Coordination BehaviorChao Li0Han Zhang1Kexin Tong2Menghua Cai3Fei Gao4Jia Yang5Yi Xu6Huaishan Wang7Hui Chen8Yu Hu9Wei He10Jianmin Zhang11Department of Immunology, CAMS Key Laboratory T Cell and Cancer Immunotherapy, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Medical Molecular Biology, Beijing 100005, ChinaDepartment of Immunology, CAMS Key Laboratory T Cell and Cancer Immunotherapy, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Medical Molecular Biology, Beijing 100005, ChinaDepartment of Immunology, CAMS Key Laboratory T Cell and Cancer Immunotherapy, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Medical Molecular Biology, Beijing 100005, ChinaDepartment of Immunology, CAMS Key Laboratory T Cell and Cancer Immunotherapy, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Medical Molecular Biology, Beijing 100005, ChinaDepartment of Immunology, CAMS Key Laboratory T Cell and Cancer Immunotherapy, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Medical Molecular Biology, Beijing 100005, ChinaDepartment of Immunology, CAMS Key Laboratory T Cell and Cancer Immunotherapy, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Medical Molecular Biology, Beijing 100005, ChinaDepartment of Immunology, CAMS Key Laboratory T Cell and Cancer Immunotherapy, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Medical Molecular Biology, Beijing 100005, ChinaDepartment of Immunology, CAMS Key Laboratory T Cell and Cancer Immunotherapy, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Medical Molecular Biology, Beijing 100005, ChinaDepartment of Immunology, CAMS Key Laboratory T Cell and Cancer Immunotherapy, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Medical Molecular Biology, Beijing 100005, ChinaDepartment of Immunology, CAMS Key Laboratory T Cell and Cancer Immunotherapy, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Medical Molecular Biology, Beijing 100005, ChinaDepartment of Immunology, CAMS Key Laboratory T Cell and Cancer Immunotherapy, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Medical Molecular Biology, Beijing 100005, ChinaDepartment of Immunology, CAMS Key Laboratory T Cell and Cancer Immunotherapy, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Medical Molecular Biology, Beijing 100005, ChinaThorase belongs to the AAA+ ATPase family, which plays a critical role in maintaining cellular homeostasis. Our previous work reported that Thorase was highly expressed in brain tissue, especially in the cerebellum. However, the roles of Thorase in the cerebellum have still not been characterized. In this study, we generated conditional knockout mice (cKO) with Thorase deletion in Purkinje cells. Thorase cKO mice exhibited cerebellar degenerative diseases-like behavior and significant impairment in motor coordination. Thorase deletion resulted in more Purkinje neuron apoptosis, leading to Purkinje cell loss in the cerebellum of Thorase cKO mice. We also found enhanced expression of the inflammatory protein ASC, IL-1β, IL-6 and TNF-α in the Thorase cKO cerebellum, which contributed to the pathogenesis of cerebellar degenerative disease. Our findings provide a better understanding of the role of Thorase in the cerebellum, which is a theoretical basis for Thorase as a therapeutic drug target for neurodegenerative diseases.https://www.mdpi.com/2073-4409/12/16/2032ThorasecerebellumPurkinje cellsneuroinflammationneurodegenerative disease |
| spellingShingle | Chao Li Han Zhang Kexin Tong Menghua Cai Fei Gao Jia Yang Yi Xu Huaishan Wang Hui Chen Yu Hu Wei He Jianmin Zhang Genetic Deletion of Thorase Causes Purkinje Cell Loss and Impaired Motor Coordination Behavior Cells Thorase cerebellum Purkinje cells neuroinflammation neurodegenerative disease |
| title | Genetic Deletion of Thorase Causes Purkinje Cell Loss and Impaired Motor Coordination Behavior |
| title_full | Genetic Deletion of Thorase Causes Purkinje Cell Loss and Impaired Motor Coordination Behavior |
| title_fullStr | Genetic Deletion of Thorase Causes Purkinje Cell Loss and Impaired Motor Coordination Behavior |
| title_full_unstemmed | Genetic Deletion of Thorase Causes Purkinje Cell Loss and Impaired Motor Coordination Behavior |
| title_short | Genetic Deletion of Thorase Causes Purkinje Cell Loss and Impaired Motor Coordination Behavior |
| title_sort | genetic deletion of thorase causes purkinje cell loss and impaired motor coordination behavior |
| topic | Thorase cerebellum Purkinje cells neuroinflammation neurodegenerative disease |
| url | https://www.mdpi.com/2073-4409/12/16/2032 |
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