Equilibrative nucleoside transporter 3 supports microglial functions and protects against the progression of Huntington's disease in the mouse model

Ying Sui Lu, Wei Chien Hung, Yu Ting Hsieh, Pei Yuan Tsai, Tsai Hsien Tsai, Hsiu Han Fan, Ya Gin Chang, Hui Kuei Cheng, Shen Yan Huang, Hsin Chuan Lin, Yan Hua Lee, Tzu Hsiang Shen, Bing Yu Hung, Jin Wu Tsai, Ivan Dzhagalov, Irene Han Juo Cheng, Chun Jung Lin, Yijuang Chern, Chia Lin Hsu*

*此作品的通信作者

研究成果: Article同行評審

摘要

Huntington's disease (HD) is a hereditary neurodegenerative disorder characterized by involuntary movements, cognitive deficits, and psychiatric symptoms. Currently, there is no cure, and only limited treatments are available to manage the symptoms and to slow down the disease's progression. The molecular and cellular mechanisms of HD's pathogenesis are complex, involving immune cell activation, altered protein turnover, and disturbance in brain energy homeostasis. Microglia have been known to play a dual role in HD, contributing to neurodegeneration through inflammation but also enacting neuroprotective effects by clearing mHTT aggregates. However, little is known about the contribution of microglial metabolism to HD progression. This study explores the impact of a microglial metabolite transporter, equilibrative nucleoside transporter 3 (ENT3), in HD. Known as a lysosomal membrane transporter protein, ENT3 is highly enriched in microglia, with its expression correlated with HD severity. Using the R6/2 ENT3−/− mouse model, we found that the deletion of ENT3 increases microglia numbers yet worsens HD progression, leading to mHTT accumulation, cell death, and disturbed energy metabolism. These results suggest that the delicate balance between microglial metabolism and function is crucial for maintaining brain homeostasis and that ENT3 has a protective role in ameliorating neurodegenerative processes.

原文English
頁(從 - 到)413-429
頁數17
期刊Brain, Behavior, and Immunity
120
DOIs
出版狀態Published - 8月 2024

指紋

深入研究「Equilibrative nucleoside transporter 3 supports microglial functions and protects against the progression of Huntington's disease in the mouse model」主題。共同形成了獨特的指紋。

引用此