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    Cell cultures from animal models of Alzheimer's disease for screening and testing drug efficacy
    3.
    发明申请
    Cell cultures from animal models of Alzheimer's disease for screening and testing drug efficacy 审中-公开
    来自阿尔茨海默病动物模型的细胞培养物用于筛选和测试药物功效

    公开(公告)号：US20050172344A1

    公开(公告)日：2005-08-04

    申请号：US10980922

    申请日：2004-11-03

    申请人： Ottavio Arancio ,  Paul Mathews ,  Stephen Schmidt ,  Ralph Nixon ,  Fortunato Battaglia ,  Fabrizio Trinchese ,  Shumin Liu

    发明人： Ottavio Arancio ,  Paul Mathews ,  Stephen Schmidt ,  Ralph Nixon ,  Fortunato Battaglia ,  Fabrizio Trinchese ,  Shumin Liu

    IPC分类号： A01K67/027 ,  C12N5/06 ,  G01N33/50 ,  G01N33/68

    CPC分类号： G01N33/502 ,  A01K2217/05 ,  A01K2227/105 ,  A01K2267/0312 ,  G01N33/5008 ,  G01N33/5014 ,  G01N33/5058 ,  G01N33/6896

    摘要： The present invention describes a dissociated cell culture system comprising cells of the hippocampus, one of the brain areas affected by Alzheimer's Disease (AD) or amyloid beta-related diseases. This culture system comprises hippocampal neuronal and glial cells from animal models of AD, particularly, but not limited to, double transgenic mice expressing both the human APP mutation (K670N:M671L) (mAPP), and the human PS1 mutation (M146L) (mPS1), and serves as a powerful tool for the screening and testing of compounds and substances, e.g., drugs, for their ability to affect, treat, or prevent AD or β-amyloid-related diseases. The effects of a test substance on the cells in this culture system can be quantitatively assessed to determine if the test substance affects the cells biochemically and/or electrophysiologically, and/or optically, and/or immunocytochemically. The present in vitro culture system is advantageous for AD drug screening, because it is rapid and efficient. By contrast, even in the fastest animal model of AD, pathology does not start before the end of the second month. If such in vivo animal models are used, it is necessary to wait at least the two month time duration or longer to test for drug efficacy for AD treatment or prevention. At the same time the present invention provides a tool for production of amyloid-beta that can be used for electrophysiological, behavioral, and toxicological studies.

    摘要翻译： 本发明描述了解离的细胞培养系统，其包括海马细胞，受阿尔茨海默病（AD）或淀粉样蛋白β相关疾病影响的脑区之一。 该培养系统包括来自AD的动物模型的海马神经元和神经胶质细胞，特别但不限于表达人APP突变（K670N：M671L）（mAPP）和人PS1突变（M146L）（mP1）的双转基因小鼠 ），并且用作筛选和测试化合物和物质（例如药物）对其影响，治疗或预防AD或β-淀粉样蛋白相关疾病的能力的有力工具。 可以定量评估测试物质对该培养系统中细胞的影响，以确定测试物质是否通过生物化学和/或电生理学和/或光学和/或免疫细胞化学方法影响细胞。 目前的体外培养体系对于AD药物筛选是有利的，因为它是快速和有效的。 相比之下，即使在AD的最快动物模型中，病理学也不会在第二个月之前开始。 如果使用这样的体内动物模型，则需要等待至少两个月的持续时间或更长时间来测试AD治疗或预防的药物功效。 同时，本发明提供了可用于电生理，行为和毒理学研究的淀粉样蛋白-β生产工具。