Identification of AOSC-binding proteins in neurons
Identification of AOSC-binding proteins in neurons
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神经元中 AOSC 结合蛋白的鉴定
DOI：
10.1007/s00343-008-0394-8
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发表时间：
2008-11-01
影响因子：
--
通讯作者：
Geng Meiyu
中科院分区：
文献类型：
--
作者：
Liu Ming;Nie Qin;Geng Meiyu
酸性寡糖糖链（AOSC）是一种从褐藻多糖中提取的d -甘露醛酸寡糖，作为抗阿尔茨海默病（AD）候选药物已在中国完成I期临床试验。神经元中aosc结合蛋白的鉴定对了解其作用机制具有重要意义。通过共聚焦显微镜、亲和层析、液相色谱-串联质谱（LC-MS/MS）分析，确定神经元中AOSC的结合蛋白介导其抗ad活性。共聚焦显微镜分析表明，AOSC以浓度、时间和温度依赖的方式与SH-SY5Y细胞结合。亲和层析纯化AOSC结合蛋白，LC-MS/MS分析鉴定AOSC结合蛋白。结果表明，AOSC有349种蛋白结合，包括网格蛋白、衔接蛋白-2 （AP-2）和淀粉样蛋白前体蛋白（APP）。这些结果表明，AOSC结合/进入神经元可能是抗ad活性的原因。
Acidic oligosaccharide sugar chain (AOSC), a D-mannuronic acid oligosaccharide, derived from brown algae polysaccharide, has been completed Phase I clinical trial in China as an anti-Alzheimer's Disease (AD) drug candidate. The identification of AOSC-binding protein(s) in neurons is very important for understanding its action mechanism. To determine the binding protein(s) of AOSC in neurons mediating its anti-AD activities, confocal microscopy, affinity chromatography, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis were used. Confocal microscopy analysis shows that AOSC binds to SH-SY5Y cells in concentration-, time-, and temperature-dependent fashions. The AOSC binding proteins were purified by affinity chromatography and identified by LC-MS/MS analysis. The results showed that there are 349 proteins binding AOSC, including clathrin, adaptor protein-2 (AP-2) and amyloid precursor protein (APP). These results suggest that the binding/entrance of AOSC to neurons is probably responsible for anti-AD activities.