The intracellular domain of amyloid precursor protein induces neuron-specific apoptosis
The intracellular domain of amyloid precursor protein induces neuron-specific apoptosis
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DOI：
10.1016/j.neulet.2008.08.034
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发表时间：
2008-10
影响因子：
2.5
通讯作者：
K. Nakayama;Takeshi Ohkawara;M. Hiratochi;C. Koh;H. Nagase
中科院分区：
文献类型：
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作者：
K. Nakayama;Takeshi Ohkawara;M. Hiratochi;C. Koh;H. Nagase
尽管淀粉样前体蛋白（APP）在阿尔茨海默病中发挥着核心作用，但该蛋白的生理功能尚未完全阐明。 APP 同源物在进化过程中显示出胞内结构域的显着序列保守性，这可能反映了 APP 胞内结构域 (AICD) 的功能重要性。为了检验这种可能性，我们建立了过表达 AICD 的胚胎癌 P19 细胞系。尽管用视黄酸处理可以将神经元从这些细胞系中分化出来，但 AICD 的过度表达会导致神经元特异性细胞死亡。此外，检测到 DNA 片段化，TUNEL 阳性细胞也是 Tuj1 阳性神经元。综上所述，我们得出结论，AICD 可以诱导神经元特异性凋亡。
Although amyloid precursor protein (APP) has central roles in Alzheimer's disease, the physiological functions of this protein have yet to be fully elucidated. APP homologues show significant sequence conservation in the intracellular domain through evolution, which may reflect the functional importance of the intracellular domain of APP (AICD). To examine this possibility, we established embryonic carcinoma P19 cell lines overexpressing AICD. Although neurons could be differentiated from these cell lines with retinoic acid treatment, overexpression of AICD gave rise to neuron-specific cell death. Furthermore, DNA fragmentation was detected and TUNEL-positive cells were also Tuj1-positive neurons. Taken together, we concluded that AICD can induce neuron-specific apoptosis.