Therapeutic Effect of Berberine on Huntington's Disease Transgenic Mouse Model.
Therapeutic Effect of Berberine on Huntington's Disease Transgenic Mouse Model.
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DOI：
10.1371/journal.pone.0134142
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Li XJ
中科院分区：
文献类型：
--
作者：
Jiang W;Wei W;Gaertig MA;Li S;Li XJ
亨廷顿病（HD）代表由错误折叠的蛋白质引起的神经退行性疾病家族。错误折叠的蛋白质以年龄依赖性的方式积累在受影响的大脑区域，导致迟发性神经变性。表达HD蛋白亨廷顿蛋白的转基因小鼠模型已被广泛用于鉴定可延缓疾病进展的治疗剂。本文报道了一种从植物中提取的有机小分子物质小檗碱（BBR）对转基因HD（N171- 82 Q）小鼠具有保护作用。我们发现BBR可以减少突变亨廷顿蛋白在培养细胞中的积累。更重要的是，口服BBR可有效缓解转基因N171- 82 Q HD小鼠的运动功能障碍，延长其存活时间。我们发现BBR可以通过增强自噬功能来促进突变亨廷顿蛋白的降解。由于BBR是一种口服药物，已安全用于治疗多种疾病，我们的研究结果表明，BBR可以在不同的HD动物模型和HD患者中进行测试，以进一步评估其治疗效果。
Huntington disease (HD) represents a family of neurodegenerative diseases that are caused by misfolded proteins. The misfolded proteins accumulate in the affected brain regions in an age-dependent manner to cause late-onset neurodegeneration. Transgenic mouse models expressing the HD protein, huntingtin, have been widely used to identify therapeutics that may retard disease progression. Here we report that Berberine (BBR), an organic small molecule isolated from plants, has protective effects on transgenic HD (N171-82Q) mice. We found that BBR can reduce the accumulation of mutant huntingtin in cultured cells. More importantly, when given orally, BBR could effectively alleviate motor dysfunction and prolong the survival of transgenic N171-82Q HD mice. We found that BBR could promote the degradation of mutant huntingtin by enhancing autophagic function. Since BBR is an orally-taken drug that has been safely used to treat a number of diseases, our findings suggest that BBR can be tested on different HD animal models and HD patients to further evaluate its therapeutic effects.