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

Author

Listed:
  • Jian Jing Siew

    (National Yang-Ming University and Academia Sinica
    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
    National Yang-Ming 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
    Academia Sinica)

  • Yijuang Chern

    (National Yang-Ming University and Academia Sinica
    Academia Sinica)

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.

Suggested Citation

  • 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, 2019. "Galectin-3 is required for the microglia-mediated brain inflammation in a model of Huntington’s disease," Nature Communications, Nature, vol. 10(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11441-0
    DOI: 10.1038/s41467-019-11441-0
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    Cited by:

    1. Abolfazl Doostparast Torshizi & Dongnhu T. Truong & Liping Hou & Bart Smets & Christopher D. Whelan & Shuwei Li, 2024. "Proteogenomic network analysis reveals dysregulated mechanisms and potential mediators in Parkinson’s disease," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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