Galectin-3 is required for the microglia-mediated brain inflammation in a model of Huntington’s disease

Jian Jing Siew, Hui-Mei Chen, Huan-Yuan Chen, Hung-Lin Chen, Chiung-Mei Chen, Bing-Wen Soong, Yih-Ru Wu, Ching-Pang Chang, Yi-Chen Chan, Chun-Hung Lin, Fu-Tong Liu and Yijuang Chern ()
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Jian Jing Siew: National Yang-Ming University and Academia Sinica
Hui-Mei Chen: Academia Sinica
Huan-Yuan Chen: Academia Sinica
Hung-Lin Chen: Academia Sinica
Chiung-Mei Chen: Chang-Gung University
Bing-Wen Soong: Taipei Medical University
Yih-Ru Wu: Chang-Gung University
Ching-Pang Chang: Academia Sinica
Yi-Chen Chan: Academia Sinica
Chun-Hung Lin: Academia Sinica
Fu-Tong Liu: National Yang-Ming University and Academia Sinica
Yijuang Chern: National Yang-Ming University and Academia Sinica

Nature Communications, 2019, vol. 10, issue 1, 1-18

Abstract: Abstract Huntington’s disease (HD) is a neurodegenerative disorder that manifests with movement dysfunction. The expression of mutant Huntingtin (mHTT) disrupts the functions of brain cells. Galectin-3 (Gal3) is a lectin that has not been extensively explored in brain diseases. Herein, we showed that the plasma Gal3 levels of HD patients and mice correlated with disease severity. Moreover, brain Gal3 levels were higher in patients and mice with HD than those in controls. The up-regulation of Gal3 in HD mice occurred before motor impairment, and its level remained high in microglia throughout disease progression. The cell-autonomous up-regulated Gal3 formed puncta in damaged lysosomes and contributed to inflammation through NFκB- and NLRP3 inflammasome-dependent pathways. Knockdown of Gal3 suppressed inflammation, reduced mHTT aggregation, restored neuronal DARPP32 levels, ameliorated motor dysfunction, and increased survival in HD mice. Thus, suppression of Gal3 ameliorates microglia-mediated pathogenesis, which suggests that Gal3 is a novel druggable target for HD.

Date: 2019
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DOI: 10.1038/s41467-019-11441-0

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