Genetic Deletion of Thorase Causes Purkinje Cell Loss and Impaired Motor Coordination Behavior

Chao Li; Han Zhang; Kexin Tong; Menghua Cai; Fei Gao; Jia Yang; Yi Xu; Huaishan Wang; Hui Chen; Yu Hu; Wei He; Jianmin Zhang

doi:10.3390/cells12162032

Genetic Deletion of Thorase Causes Purkinje Cell Loss and Impaired Motor Coordination Behavior

Cells. 2023 Aug 10;12(16):2032. doi: 10.3390/cells12162032.

Authors

Chao Li¹, Han Zhang¹, Kexin Tong¹, Menghua Cai¹, Fei Gao¹, Jia Yang¹, Yi Xu¹, Huaishan Wang¹, Hui Chen^{1

2

3}, Yu Hu^{1

2

3}, Wei He¹, Jianmin Zhang^{1

2

3}

Affiliations

¹ Department 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, China.
² Changzhou Xitaihu Institute for Frontier Technology of Cell Therapy, Changzhou 213000, China.
³ Haihe Laboratory of Cell Ecosystem, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300010, China.

Abstract

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.

Keywords: Purkinje cells; Thorase; cerebellum; neurodegenerative disease; neuroinflammation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ATPases Associated with Diverse Cellular Activities
Animals
Brain
Causality
Cerebellum*
Mice
Mice, Knockout
Purkinje Cells*

Substances

ATPases Associated with Diverse Cellular Activities

Grants and funding

This research was supported by the CAMS Initiative for Innovative Medicine (2021-I2M-1-005 and 2021-I2M-1-035), the National Natural Science Foundation of China (82071791, 31970843 and 81972886), the National Basic Research Program of China (no. 2013CB530503), the CAMS Central Public Welfare Scientific Research Institute Basal Research Expenses (2018PT32004 and 2018PT31052), and Haihe Laboratory of Cell Ecosystem Innovation Fund (HH22KYZX0028).