Journal
CELLS
Volume 12, Issue 16, Pages -Publisher
MDPI
DOI: 10.3390/cells12162032
Keywords
Thorase; cerebellum; Purkinje cells; neuroinflammation; neurodegenerative disease
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This study demonstrates the important role of Thorase in the cerebellum. By deleting Thorase gene in Purkinje cells of the cerebellum, the researchers observed cerebellar degenerative disease-like behavior and significant impairment in motor coordination in Thorase cKO mice. Thorase deletion also led to increased Purkinje neuron apoptosis and cell loss in the cerebellum, along with enhanced expression of inflammatory proteins ASC, IL-1 beta, IL-6 and TNF-alpha, which contribute to the pathogenesis of cerebellar degenerative disease.
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-1 beta, IL-6 and TNF-alpha 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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