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

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

Nat Commun. 2019 Aug 2;10(1):3473.
doi: 10.1038/s41467-019-11441-0

閱讀文章

Siew JJ1,2Chen HM2Chen HY2Chen HL2Chen CM3Soong BW4,5Wu YR3Chang CP2Chan YC6Lin CH6Liu FT1,2Chern Y7,8

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.