Effects of Edaravone on Amyloid-β Precursor Protein Processing in SY5Y-APP695 Cells
Effects of Edaravone on Amyloid-β Precursor Protein Processing in SY5Y-APP695 Cells
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DOI：
10.1007/s12640-012-9370-3
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发表时间：
2013-08-01
影响因子：
3.7
通讯作者：
Zhang, Li-Ming
中科院分区：
文献类型：
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作者：
Shen, Yue-E;Wang, Yan;Zhang, Li-Ming
先前的报道表明活性氧（ROS）参与了阿尔茨海默病（AD）的发展，最近的研究表明自由基生成系统可以调节淀粉样蛋白- β前体蛋白（APP）的加工。依达拉奉是一种新型的自由基清除剂，目前用于减轻急性脑梗死后的脑损伤。本研究以稳定转染人“瑞典”APP突变APP695 （SY5Y-APP695swe）的SH-SY5Y细胞为体外模型，研究依达拉奉对APP加工的影响。结果表明，依达拉奉处理24 h后，β -淀粉样蛋白（A β）的产生呈剂量依赖性下调。此外，依达拉奉通过增加α -分泌酶衍生的APP片段和减少β -分泌酶衍生的APP片段来调节APP加工。胰岛素降解酶（IDE）和neprilysin (NEP) mRNA和蛋白水平在给药后无明显变化。综上所述，我们的数据表明依达拉奉通过增强非淀粉样蛋白生成途径和抑制淀粉样蛋白生成途径在调节A β生成中发挥重要作用。因此，依达拉奉可能对治疗阿尔茨海默病（AD）有潜在的作用。
Previous reports have revealed that reactive oxygen species (ROS) is involved in the development of Alzheimer's disease (AD), and recent studies indicate that free radical-generating systems can regulate amyloid-beta precursor protein (APP) processing. Edaravone is a novel free radical scavenger currently used to reduce cerebral damages after acute cerebral infarction. In the present study, we used SH-SY5Y cells stably transfected with the human "Swedish" APP mutation APP695 (SY5Y-APP695swe) as an in vitro model to investigate the effect of edaravone on APP processing. The result showed that edaravone treatment for 24 h down-regulated beta-amyloid (A beta) production in a dose-dependent manner. Moreover, edaravone modulated APP processing by increasing alpha-secretase-derived APP fragments and decreasing beta-secretase-derived APP fragments. In addition, the mRNA and protein levels of insulin degrading enzyme (IDE) and neprilysin (NEP), two key A beta degrading enzymes, were not changed after edaravone administration. Taken together, our data suggested that edaravone played an important role in regulating A beta production by enhancing the non-amyloidogenic pathway and inhibiting the amyloidogenic pathway. Thus, edaravone may be potentially useful for treating Alzheimer's disease (AD).