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    Methods and compositions for inhibition of axonal degeneration by modulation of the DLK/JNK pathway
    1.
    发明授权
    Methods and compositions for inhibition of axonal degeneration by modulation of the DLK/JNK pathway 有权
    通过调节DLK / JNK途径抑制轴索变性的方法和组合物

    公开(公告)号：US08754060B2

    公开(公告)日：2014-06-17

    申请号：US13722821

    申请日：2012-12-20

    申请人： Washington University

    发明人： Aaron DiAntonio ,  Bradley R. Miller ,  Jeffrey D. Milbrandt ,  Craig A. Press

    IPC分类号： C12N15/11 ,  C12Q1/68 ,  C07H21/02 ,  C07H21/04 ,  C12N5/02 ,  C12N5/00

    CPC分类号： A61K31/713 ,  A61K31/415 ,  A61K31/7088 ,  C12Q1/48 ,  G01N2333/91205 ,  G01N2500/10

    摘要： Methods of reducing Wallerian degeneration are disclosed. These methods comprise inhibiting expression or activity of a mixed lineage kinase such as a dual leucine-zipper-bearing kinase (DLK), inhibiting expression or activity of a molecule acting downstream from DLK, such as a c-Jun N-terminal kinase (JNK), or a combination thereof. Further disclosed are methods of screening candidate compounds for DLK inhibition activity. These methods comprise providing a neuronal culture comprising a plurality of axons; contacting the culture with a candidate compound and with an axon degeneration-triggering agent; and comparing axonal degeneration in the culture to a control culture comprising the axon degeneration-triggering agent but not the candidate compound.

    摘要翻译： 公开了降低瓦勒氏变性的方法。 这些方法包括抑制混合谱系激酶的表达或活性，例如双重亮氨酸 - 拉链携带激酶（DLK），抑制DLK下游作用的分子的表达或活性，例如c-Jun N-末端激酶（JNK ）或其组合。 进一步公开的是筛选候选化合物用于DLK抑制活性的方法。 这些方法包括提供包含多个轴突的神经元培养物; 使培养物与候选化合物和轴突变性引发剂接触; 并将培养物中的轴突变性与包含轴突变性引发剂但不是候选化合物的对照培养物进行比较。