From the Menzies Research Institute Tasmania and.
From the Menzies Research Institute Tasmania and School of Medicine, University of Tasmania, Hobart, Tasmania 7000, Australia.
J Biol Chem. 2014 Nov 7;289(45):31253-61. doi: 10.1074/jbc.M114.581918. Epub 2014 Sep 12.
Amyloid-β precursor protein (APP) is well studied for its role in Alzheimer disease, although its normal function remains uncertain. It has been reported that APP stimulates the proliferation and neuronal differentiation of neural stem/progenitor cells (NSPCs). In this study we examined the role of APP in NSPC differentiation. To identify proteins that may mediate the effect of APP on NSPC differentiation, we used a gene array approach to find genes whose expression correlated with APP-induced neurogenesis. We found that the expression of neurogenin 2 (Ngn2), a basic helix-loop-helix transcription factor, was significantly down-regulated in NSPCs from APP knock-out mice (APPKO) and increased in APP transgenic (Tg2576) mice. Ngn2 overexpression in APPKO NSPCs promoted neuronal differentiation, whereas siRNA knockdown of Ngn2 expression in wild-type NSPCs decreased neuronal differentiation. The results demonstrate that APP-stimulated neuronal differentiation of NSPCs is mediated by Ngn2.
淀粉样前体蛋白（APP）在阿尔茨海默病中的作用已得到深入研究，但其正常功能仍不确定。据报道，APP 可刺激神经干细胞/祖细胞（NSPC）的增殖和神经元分化。在这项研究中，我们研究了 APP 在 NSPC 分化中的作用。为了确定可能介导 APP 对 NSPC 分化影响的蛋白，我们使用基因芯片方法来寻找与 APP 诱导神经发生相关的表达基因。我们发现，神经基因 2（Ngn2）的表达在 APP 敲除（APPKO）小鼠的 NSPC 中显著下调，而在 APP 转基因（Tg2576）小鼠中上调。在 APPKO NSPC 中过表达 Ngn2 可促进神经元分化，而在野生型 NSPC 中 siRNA 下调 Ngn2 表达则减少神经元分化。结果表明，APP 刺激 NSPC 的神经元分化是由 Ngn2 介导的。
