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机构地区:[1]Department of Molecular Pharmacology,School of Medicine and Pharmacy Ocean University of China [2]Division of Anti-tumor Pharmacology,State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences
出 处:《Chinese Journal of Oceanology and Limnology》2008年第4期394-399,共6页中国海洋湖沼学报(英文版)
基 金:Supported by National Basic Research Program of China (973 Program) (No.2003CB716400);Natural Science Foundation of China for Distingutshed Young Scholars (No.30725046);Natural Science Foundation of China (No.30472029,No.30772612);Chinese High technology Research and Development Program of China(863 Program) (No.2006AA090501)
摘 要:Acidic oligosaccharide sugar chain (AOSC), a D-mannuronic acid oligosaccharide, derived from brownalgaepolysaccharide, 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.酸的 oligosaccharide 糖链(AOSC ) , D-mannuronic 酸 oligosaccharide,源于棕色的水藻多糖,被完成了阶段我在是的中国的临床的试用 anti-Alzheimer 的疾病(广告) 药候选人。在神经原的 AOSC 有约束力的蛋白质的鉴定为理解它的行动机制是很重要的。为了在调停的神经原决定 AOSC 的有约束力的蛋白质,它的反广告活动,共焦的显微镜学,亲密关系层析,和液体层析双人脚踏车集中 spectrometry (LC-MS/MS ) 分析被使用。AOSC 在集中绑在 SH-SY5Y 房间的共焦的显微镜学分析表演 -- ,时间 -- ,并且温度依赖者时尚。AOSC 有约束力的蛋白质被亲密关系层析净化并且由 LC-MS/MS 分析识别了。结果证明有 349 蛋白质绑定 AOSC,包括 clathrin,适配器 protein-2 (AP-2 ) 和淀粉的先锋蛋白质(应用软件) 。这些结果建议到神经原的 AOSC 的绑定 / 入口为反广告活动可能负责。
关 键 词:AOSC Alzheimer's disease marine oligosaccharide binding protein(s)
分 类 号:R741[医药卫生—神经病学与精神病学]
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