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, Yijuang Chern

研究成果: 雜誌貢獻文章同行評審

55 引文 斯高帕斯(Scopus)

摘要

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.

原文英語
文章編號3473
期刊Nature Communications
10
發行號1
DOIs
出版狀態已發佈 - 十二月 1 2019

ASJC Scopus subject areas

  • 化學 (全部)
  • 生物化學、遺傳與分子生物學 (全部)
  • 物理與天文學 (全部)

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