Icariin reduces α-synuclein over-expression by promoting α-synuclein degradation
Icariin reduces α-synuclein over-expression by promoting α-synuclein degradation
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淫羊藿苷通过促进 α-突触核蛋白降解来减少 α-突触核蛋白过度表达
DOI：
10.1007/s11357-015-9811-z
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发表时间：
2015-08-01
期刊：
影响因子：
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通讯作者：
Li, Lin
中科院分区：
文献类型：
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作者：
Zhang, Lan;Shen, Cong;Li, Lin
本研究旨在探讨淫羊藿主要成分淫羊藿苷对α -突触核蛋白过表达的影响，并探讨其机制。本研究采用APPV717I转基因（Tg）小鼠和A53T α -突触核蛋白转染的PC12细胞。反转录PCR （RT-PCR）检测无核蛋白mRNA的含量。Western blotting和免疫组织化学检测α -突触核蛋白、parkin、泛素羧基末端水解酶L1 （UCH-L1）和热休克蛋白70 （HSP70）的表达。10月龄APP Tg小鼠海马内无核蛋白表达升高，Parkin、UCH-L1、HSP70表达降低。6月龄（4 ~ 10月龄）ig淫羊藿苷（30和100 μ mol/ kg）可降低APP Tg小鼠海马α -突触核蛋白的表达，升高Parkin、UCH-L1和HSP70的表达。淫羊藿苷（40和80 μ M）与A53T α -突触核蛋白转染的PC12细胞孵育24 h后，模型组和淫羊藿苷处理组无明显差异，但单体和四聚体α -突触核蛋白表达均降低。在α -突触核蛋白下调的同时，淫羊藿苷（40和80 μ M）升高了转染A53T α -突触核蛋白的细胞中Parkin、UCH-L1和HSP70的表达。淫羊藿苷在体内和体外均抑制α -突触核蛋白的过表达。淫羊藿苷的作用机制可能与上调泛素蛋白酶体系统中Parkin和UCH-L1的表达以及分子伴侣中HSP70的表达，从而促进α -突触核蛋白的降解有关。提示淫羊藿苷可能具有治疗阿尔茨海默病（AD）和其他突触核蛋白病的潜力。
The objectives of this study are to investigate the effects of icariin (a main component extracted from Epimedium) on over-expression of alpha-synuclein and to explore the underlying mechanisms. APPV717I transgenic (Tg) mice and A53T alpha-synuclein-transfected PC12 cells were used in this study. The content of asynuclein mRNA was determined by reversetranscription PCR (RT-PCR). Western blotting and immunohistochemistry were used to detect the protein expression of alpha-synuclein, parkin, ubiquitin carboxyterminal hydrolase L1 (UCH-L1), and heat shock protein 70 (HSP70). In 10-month-old APP Tg mice, asynuclein expression was increased, and the expression of Parkin, UCH-L1, and HSP70 was decreased in the hippocampus. Intragastrical administration of icariin (30 and 100 mu mol/ kg) for 6 months (from 4 to 10 months old) decreased alpha-synuclein expression and increased the expression of Parkin, UCH-L1, and HSP70 in the hippocampus of APP Tg mice. Incubation of icariin (40 and 80 mu M) with A53T alpha-synuclein-transfected PC12 cells for 24 h showed no difference in the expressions of asynuclein mRNA among model group and icariintreated groups, but decreased alpha-synuclein protein expression in both monomer and tetramer. Along with the downregulation of alpha-synuclein, icariin (40 and 80 mu M) elevated the expression of Parkin, UCH-L1, and HSP70 in A53T alpha-synuclein-transfected cells. Icariin inhibited the over-expression of alpha-synuclein both in vivo and in vitro. The mechanism of icariin may be related to upregulate Parkin and UCH-L1 expression in ubiquitinproteasome system and HSP70 in molecular chaperone, thus enhancing the degradation of alpha-synuclein. It is suggested that icariin may have the potential to treat Alzheimer's disease (AD) and other synucleinopathies.