Quercetin ameliorates Aβ toxicity in Drosophila AD model by modulating cell cycle-related protein expression.
Quercetin ameliorates Aβ toxicity in Drosophila AD model by modulating cell cycle-related protein expression.
复制标题
槲皮素通过调节细胞周期相关蛋白表达改善果蝇 AD 模型中的 Aβ 毒性
DOI：
10.18632/oncotarget.11963
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发表时间：
2016-10-18
期刊：
影响因子：
--
通讯作者：
Yuan L
中科院分区：
文献类型：
--
作者：
Kong Y;Li K;Fu T;Wan C;Zhang D;Song H;Zhang Y;Liu N;Gan Z;Yuan L
阿尔茨海默病 (AD) 是一种常见的神经退行性疾病，其特征是 β 淀粉样蛋白 (Aβ) 沉积和神经原纤维缠结。据报道，生物类黄酮槲皮素可以改善秀丽隐杆线虫和小鼠的 AD 表型。然而，槲皮素改善作用的机制尚未完全清楚。果蝇模型可以重现类似 AD 的表型，例如寿命缩短、运动能力受损以及学习和记忆缺陷。因此，在本研究中，我们在果蝇模型中研究了槲皮素对 AD 的影响并探讨了其潜在机制。我们发现槲皮素可以有效干预体内AD的发病机制。机制研究表明，槲皮素可以恢复受 Aβ 积累干扰的基因表达，例如那些参与细胞周期和 DNA 复制的基因。选择重要的细胞周期蛋白Cyclin B来测试其是否参与槲皮素的AD改善作用。我们发现大脑中的细胞周期蛋白 B RNAi 可以减轻 AD 表型。综上所述，目前的研究表明槲皮素的神经保护作用至少部分是通过靶向细胞周期相关蛋白来介导的。
Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by β amyloid (Aβ) deposition and neurofibril tangles. It has been reported that a bioflavonoid, quercetin, could ameliorate AD phenotypes in C. elegans and mice. However, the mechanism underlying the ameliorative effect of quercetin is not fully understood yet. Drosophila models could recapitulate AD-like phenotypes, such as shortened lifespan, impaired locomotive ability as well as defects in learning and memory. So in this study, we investigated the effects of quercetin on AD in Drosophila model and explored the underlying mechanisms. We found quercetin could effectively intervene in AD pathogenesis in vivo. Mechanism study showed quercetin could restore the expression of genes perturbed by Aβ accumulation, such as those involved in cell cycle and DNA replication. Cyclin B, an important cell cycle protein, was chosen to test whether it participated in the AD ameliorative effects of quercetin. We found that cyclin B RNAi in the brain could alleviate AD phenotypes. Taken together, the current study suggested that the neuroprotective effects of quercetin were mediated at least partially by targeting cell cycle-related proteins.