摘要
背景：多种蛋白质被认为是阿尔茨海默病（AD）患者和小鼠模型的影像学、遗传学或蛋白质组学研究的潜在诊断标志物。然而，对于AD先兆诊断生物标志物仍在研究中，如在AD发病机制的分子变化的先兆。 目的：在本研究中，我们旨在分析APPSw早期的蛋白质组变化，IND小鼠，并对有趣的蛋白功能进行进一步研究。 方法：采用同位素标记相对和绝对定量（iTRAQ）与质谱联用的方法检测IND小鼠海马APPsw早期蛋白质组的变化。用定量逆转录聚合酶链反应（RT-PCR）和免疫印迹法进行进一步验证。最后，有趣的蛋白质β-血影蛋白 和 Rab3a APP转运和加工的功能由在N2a细胞中稳定表达的β-淀粉前体蛋白（APP）shRNA干扰测试。 结果：iTRAQ和RT-PCR结果显示，氧化应激，髓鞘形成，星形胶质细胞的激活，mTOR信号和Rab3-依赖的受体转运AD进展的早期阶段详细的分子改变。敲除β -spectrin 和 Rab3a最后导致增加受体片段的生成，说明β -spectrin 和 Rab3a在调节受体生成过程中扮演着关键角色。 结论：我们的研究首次揭示了AD小鼠模型早期海马组织蛋白质组的变化。除了进一步了解AD早期发病的分子改变和功能级联反应外，我们的发现还提高了潜在的生物标记物和AD早期治疗靶点的可能性。
关键词: iTRAQ，海马，前期症状，APPSw，Ind小鼠，APP/PS1小鼠，阿尔茨海默病
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