Sheng Baiyang, Song Bo, Zheng Zhenhuan, Zhou Fangfang, Lu Guangyuan, Zhao Nanming, Zhang Xiufang, Gong Yandao
State Key Laboratory of Biomembrane and Membrane Biotechnology, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China.
Neurosci Lett. 2009 Feb 6;450(3):327-31. doi: 10.1016/j.neulet.2008.11.046. Epub 2008 Nov 27.
Amyloid precursor protein (APP) is expressed ubiquitously but its wrong cleavage only occurs in central nervous system. In this research, overexpression of wild type human APP695 was found to stimulate the adhesion and migration of N2a cells. In the cells co-transfected by familial Alzheimer's disease (FAD)-linked Swedish mutant of APP695 gene plus big up tri, openE9 deleted presenilin1 gene (N2a/Swe. big up tri, open9), however, this stimulating function was impaired compared to that in the cells co-transfected by Swedish mutant of APP695 gene plus dominant negative mutant of presenilin1 D385A gene (N2a/Swe.385). Furthermore, it was also found that the phosphorylation of FAK Tyr-861 and GSK-3beta Ser-9 was reduced in N2a/Swe.Delta9 cells, which can be possibly taken as a reasonable explanation for the underlying mechanism. Our results suggest that impaired cell adhesion and migration induced by abnormal cleavage of APP could contribute to the pathological effects in FAD brain.
淀粉样前体蛋白（APP）在全身广泛表达，但其错误切割仅发生在中枢神经系统。在本研究中，发现野生型人APP695的过表达可刺激N2a细胞的黏附与迁移。然而，在共转染家族性阿尔茨海默病（FAD）相关的APP695基因瑞典突变体加大肠杆菌素、开放阅读框E9缺失的早老素1基因（N2a/Swe.大肠菌素，开放阅读框9）的细胞中，与共转染APP695基因瑞典突变体加早老素1 D385A基因显性负性突变体（N2a/Swe.385）的细胞相比，这种刺激功能受损。此外，还发现N2a/Swe.Δ9细胞中黏着斑激酶Tyr-861和糖原合成酶激酶-3β Ser-9的磷酸化水平降低，这可能是其潜在机制的合理解释。我们的结果表明，APP异常切割诱导的细胞黏附与迁移受损可能导致FAD脑的病理效应。
