摘要
背景：阿尔茨海默病（AD）与关键脑丝裂原活化蛋白激酶（MAPK）信号级联的损伤有关，包括p38，c-Jun N末端激酶（JNK），ERK和Akt通路。载脂蛋白E4（ApoE4）是AD中最常见的遗传风险因子。 目的：研究MAPK信号通路在介导apoE4的病理作用中发挥作用的程度，并可通过实验操作逆转。 方法：使用来自幼稚和病毒处理的apoE3和apoE4靶向替代小鼠的海马组织的免疫印迹测定获得的MAPK信号传导途径因子的总水平和活化的测量。 结果：ApoE4小鼠显示出与应激相关的p38和JNK途径的强烈活化以及Akt活性的相应降低，其与GSK3β的激活和tau蛋白过度磷酸化相关。对ERK途径没有影响。我们先前已经证明了apoE4相关的病理学，即;通过利用表达VEGF的腺相关病毒上调VEGF水平，可以逆转Aβ的积累，过度磷酸化的tau，突触损伤和降低的VEGF水平。利用这种方法，我们评估了apoE4的AD标志和突触病理与相应的MAPK信号传导效应相关的程度。这表明通过VEGF治疗逆转apoE4驱动的病理学与p38和Akt相关作用的逆转相关。 结论：总之，这些结果表明p38和Akt通路在介导apoE4在海马中的AD相关病理学作用中起作用。
关键词: 阿尔茨海默病（AD），载脂蛋白E4（apoE4），VEGF，MAPK，信号传导，腺相关病毒，海马，靶向替代小鼠。
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