[Objective] The research aimed to study the effects of the intracellular domain of APP family on the directional differentiation of neuron. [Method ] Neural stem cells were isolated and cultured in vitro, which were then transfected with plasmids containing the intracellular domains of APP family for overexpression. Their effects on the directional differentiation of neural stem cells into neurons were studied. [Result ] The over-expression of the intracellular domain of APP protein family can inhibit the differentiation of neural stem cells into neurons, and the effects of intracellular segments of APP and APLP2 were particularly significant. Mutagenesis experiments showed that it was necessary to release 31 amino acid terminal fragment through Capase hydrolysis in this process. The directional differentiation of neural stem cells into neuron cells was controlled through releasing APP-ICD31 by the intracellular domain of APP family. [Conclusion] This research further proved the relationship between APP protein and the incidence of Alzheimers disease,and provided new targets for the treatment of Alzheimers disease.%[目的]研究APP家族胞内段时神经细胞定向分化的影响.[方法]通过分离体外培养神经干细胞,转染导入APP蛋白家族胞内段以过表达后,研究其对神经干细胞向神经元定向分化的影响.[结果]APP家族蛋白胞内段的过表达可以抑制神经干细胞向神经元细胞的分化,其中APP和APLP2胞内段的影响尤为显著.突变试验表明,通过Capase水解释放末端31氧基酸片断是这个过程必需的.APP家族胞内段是通过释放APP-ICD31来抑制神经干细胞向神经元细胞的定向分化.[结论]该研究进一步证实了APP蛋白和老年痴呆病发生的联系,也为老年痴呆症的治疗提供新的靶点.
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