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Abstract：
Amyloid precursor protein (APP) has been widely studied due to its association with Alzheimer\'s disease (AD). However, the physiological functions of APP are still largely unexplored. APP is a transmembrane glycoprotein whose expression in humans is abundant in the central nervous system. Specifically, several studies have revealed the high expression of APP during brain development. Previous studies in our laboratory revealed that a transient increase in APP expression induces early cell cycle exit of human neural stem cells (hNSCs) and directs their differentiation towards glial cells (gliogenesis) while decreasing their differentiation towards neurons (neurogenesis). In the present study, we have evaluated the intrinsic cellular effects of APP down-expression (using siRNA) on cell death, cell proliferation, and cell fate specification of hNSCs. Our data indicate that APP silencing causes cellular effects opposite to those obtained in previous APP overexpression assays, inducing cell proliferation in hNS1 cells (a model line of hNSCs) and favoring neurogenesis instead of gliogenesis in these cells. In addition, we have analyzed the gene and protein expression levels of β-Catenin as a possible molecule involved in these cellular effects. These data could help to understand the biological role of APP, which is necessary to deepen the knowledge of AD.
摘要：
淀粉样前体蛋白(APP)由于其与阿尔茨海默病(AD)的相关性而被广泛研究。然而,APP的生理功能在很大程度上仍未被探索。APP是一种跨膜糖蛋白，其在人类中的表达在中枢神经系统中丰富。具体来说,多项研究表明，APP在大脑发育过程中的高表达。我们实验室的先前研究表明，APP表达的瞬时增加会诱导人类神经干细胞（hNSC）的早期细胞周期退出，并引导其分化为神经胶质细胞（神经胶质发生），同时降低其分化为神经元（神经发生）。在本研究中,我们已经评估了APP下调（使用siRNA）对细胞死亡的内在细胞效应，细胞增殖，和hNSC的细胞命运规范。我们的数据表明，APP沉默引起的细胞效应与先前APP过表达试验中获得的细胞效应相反，诱导hNS1细胞（hNSC模型系）中的细胞增殖，并有利于这些细胞中的神经发生而不是神经胶质发生。此外,我们已经分析了β-Catenin的基因和蛋白质表达水平，β-Catenin可能是参与这些细胞效应的分子。这些数据可以帮助理解APP的生物学作用，这对于加深对AD的认识是必要的。
