Galectin-3 is required for the microglia-mediated brain inflammation in a model of Huntington’s disease (Nat Commun. 2019, 10(1):3473.)

報告日期: 2019/10/01
報告時間: 17:10/18:00
報告學生: Irwin Ivandi Puc
講評老師: 楊尚訓
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Galectin-3 is required for the microglia-mediated brain inflammation in a model of Huntington’s disease

Siew et al. Nature Communication 2019 10:1038

Speaker: Irwin Puc (傅立宇)                                       Time: 17:00-18:00, October. 1, 2019

Commentator: Dr. Yang-Shang Hsun (楊尚訓)             Place: Room 603

Abstract:

Huntington disease (HD) is an incurable progressive neurodegenerative, autosomal dominant inherited disorder associated with movement dysfunction and cell loss of a group of nerve cell clusters, called nuclei in the basal ganglia. Of note, these cells play a crucial role in behavior control and movement. The mutation causing HD is an abnormal CAG expansion in the IT15(HTT) gene coding for the protein huntingtin (HTT) which is expressed ubiquitously in human tissues. When the expanded CAG repeat exceeds 36, it is translated into a mutated form of the huntingtin protein (mHTT) which jeopardizes important cellular machinery in various types of brain cells, moreover the amount of CAG repeat present correlates with the time of onset of the disease. Clinically, the symptoms of HD include impairment of motor and cognitive functions, body weight loss, brain atrophy and shortened lifespan. Chronic inflammation has been associated in the pathogenesis of various neurological diseases and HD is no different. Microglia cells are the major cells responsible for inflammatory responses in the brain, various studies have pinpointed that the abnormal activation of microglia contribute to HD pathogenesis. In this published journal the authors take the opportunity to highlight the need for further studies involving this devastating disease. Moreover, appropriate biomarkers have yet to be defined for accurate and sensitive evaluation of HD progression. Their results demonstrated that Galectin-3 (Gal3), a member of the multifunctional beta-galactoside-binding protein, is up-regulated in the brains and plasma of HD patients and HD mouse models, correlating with disease severity. The up-regulated Gal3 formed puncta in damaged lysosomes and contributed to inflammation via NFκB- and NLRP3 inflammasome-dependent pathways. Knockdown of Gal3 not only suppressed inflammation but reduced mHTT aggregation, improve motor function and increased survival in HD mice. Therefore, there findings provide a new mechanistic insight into the role of Gal3 in HD, suggesting that Gal3 might possibly be a potent target for therapeutic intervention in HD.

References:

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