Jiang Wenxiao, Wei Wenjie, Gaertig Marta A, Li Shihua, Li Xiao-Jiang
Department of Human Genetics, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, United States of America; Graduate Program of Microbiology and Molecular Genetics, Emory University, Atlanta, GA 30322, United States of America.
Department of Human Genetics, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, United States of America; Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430032, China.
PLoS One. 2015 Jul 30;10(7):e0134142. doi: 10.1371/journal.pone.0134142. eCollection 2015.
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.
亨廷顿舞蹈症(HD)是一类由错误折叠蛋白引起的神经退行性疾病。错误折叠的蛋白以年龄依赖的方式在受影响的脑区积累,导致迟发性神经退行性变。表达亨廷顿舞蹈症蛋白(亨廷顿蛋白)的转基因小鼠模型已被广泛用于鉴定可能延缓疾病进展的疗法。在此,我们报告从植物中分离出的有机小分子黄连素(BBR)对转基因HD(N171-82Q)小鼠具有保护作用。我们发现BBR可减少培养细胞中突变型亨廷顿蛋白的积累。更重要的是,口服BBR可有效缓解运动功能障碍并延长转基因N171-82Q HD小鼠的生存期。我们发现BBR可通过增强自噬功能促进突变型亨廷顿蛋白的降解。由于BBR是一种已被安全用于治疗多种疾病的口服药物,我们的研究结果表明,可在不同的HD动物模型和HD患者身上对BBR进行测试,以进一步评估其治疗效果。