Bim contributes to the progression of Huntington's disease-associated phenotypes.
Bim contributes to the progression of Huntington's disease-associated phenotypes.
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DOI：
10.1093/hmg/ddz275
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发表时间：
2019-12
影响因子：
3.5
通讯作者：
S. Roberts;Tracey Evans;Yi Yang;Yuhua Fu;R. Button;Rebecca J. Sipthorpe;Katrina Cowan;Evelina Valionyte;O. Anichtchik;Huiliang Li;B. Lu;S. Luo
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文献类型：
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作者：
S. Roberts;Tracey Evans;Yi Yang;Yuhua Fu;R. Button;Rebecca J. Sipthorpe;Katrina Cowan;Evelina Valionyte;O. Anichtchik;Huiliang Li;B. Lu;S. Luo
亨廷顿氏病（HD）是由亨廷顿蛋白（HTT）中的多聚谷氨酰胺（polyQ）通道扩展引起的神经退行性疾病。突变体HTT（mHTT）毒性是由其聚集/寡聚化引起的。纹状体是最脆弱的区域，尽管所有脑区域在疾病中都会发生神经元变性。在这里，我们表明，Bim的水平，BH 3-唯一的蛋白质，显着增加HD人类死后和HD小鼠纹状体，与神经元死亡。Bim减少改善HD细胞中的mHTT神经毒性。在HD小鼠模型中，杂合Bim敲除显著减轻mHTT积累和神经元死亡，改善疾病相关表型和寿命。因此，Bim可能有助于HD的进展。
Huntington's disease (HD) is a neurodegenerative disorder caused by an expanded polyglutamine (polyQ) tract in the huntingtin (HTT) protein. Mutant HTT (mHTT) toxicity is caused by its aggregation/oligomerisation. The striatum is the most vulnerable region, although all brain regions undergo neuronal degeneration in the disease. Here we show that the levels of Bim, a BH3-only protein, are significantly increased in HD human post-mortem and HD mouse striata, correlating with neuronal death. Bim reduction ameliorates mHTT neurotoxicity in HD cells. In the HD mouse model, heterozygous Bim knockout significantly mitigates mHTT accumulation and neuronal death, ameliorating disease-associated phenotypes and lifespan. Therefore, Bim could contribute to the progression of HD.