Lycium barbarum polysaccharide attenuates the cytotoxicity of mutant huntingtin and increases the activity of AKT
Lycium barbarum polysaccharide attenuates the cytotoxicity of mutant huntingtin and increases the activity of AKT
复制标题
枸杞多糖减弱突变亨廷顿蛋白的细胞毒性并增加 AKT 活性
DOI：
10.1016/j.ijdevneu.2016.05.004
复制
发表时间：
2016-08-01
影响因子：
1.8
通讯作者：
Li, He
中科院分区：
文献类型：
--
作者：
Fang, Fang;Peng, Ting;Li, He
亨廷顿病 (HD) 是一种遗传性神经退行性疾病，由编码亨廷顿蛋白 (Htt) 的基因中 CAG 重复序列的异常扩增引起。 AKT 磷酸化减少和 AKT 活性抑制已被证明与突变 Htt (mHtt) 诱导的细胞死亡有关。据报道，枸杞多糖（LBP）是枸杞的主要生物活性成分，在神经损伤（包括神经退行性疾病）中具有神经保护作用。在此，我们报道 LBP 治疗可以增加稳定表达含有 160 个谷氨酰胺重复序列的 mHtt 的 HEK293 细胞的活力，并显着改善 HD 转基因小鼠的运动行为和寿命。此外，我们发现在 LBP 处理的表达 mHtt 的 HEK293 细胞中，mHtt 水平降低，AKT Ser473 (p-AKT-Ser473) 磷酸化显着增加。我们还发现，LBP 治疗可增加 HD 转基因小鼠皮层、海马和纹状体中的 p-AKT-Ser473 并降低 mHtt。 p-GSK3 beta-Ser9 的磷酸化水平在培养细胞和 HD 转基因小鼠中均保持不变。我们的研究结果表明，LBP 通过激活 AKT 和降低 mHtt 水平来减轻 mHtt 的细胞毒性，这表明 LBP 可能对治疗 HD 有潜在作用。 (C) 2016 ISDN。由爱思唯尔有限公司出版。保留所有权利。
Huntington's disease (HD) is an inherited neurodegenerative disease that is caused by the abnormal expansion of CAG repeats in the gene encoding huntingtin (Htt). Reduced AKT phosphorylation and inhibited AKT activity have been shown to be involved in mutant Htt (mHtt)-induced cell death. Lycium barbarum polysaccharide (LBP), the main bioactive component of Lycium barbarum, reportedly has neuroprotective roles in neural injuries, including neurodegenerative diseases. Here, we report that treatment with LBP can increased the viability of HEK293 cells that stably expressed mHtt containing 160 glutamine repeats and significantly improved motor behavior and life span in HD-transgenic mice. Furthermore, we found that in LBP-treated HEK293 cells expressing mHtt, mHtt levels were reduced and the phosphorylation of AKT at Ser473 (p-AKT-Ser473) was significantly increased. We also found that treatment with LBP increased p-AKT-Ser473 and decreased mHtt in the cortex, hippocampus and striatum in HD-transgenic mice. The level of phosphorylation of p-GSK3 beta-Ser9 remained unchanged in both cultured cells and HD-transgenic mice. Our findings suggest that LBP alleviates the cytotoxicity of mHtt by activating AKT and reducing mHtt levels, indicating that LBP may be potentially useful for treating HD. (C) 2016 ISDN. Published by Elsevier Ltd. All rights reserved.