Chen Z, Duan R-S, Lepécheur M, Paly E, London J, Zhu J
Division of Experimental Geriatrics, Department of Neurotec, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
Apoptosis. 2005 May;10(3):499-502. doi: 10.1007/s10495-005-1879-y.
Peptides derived from proteolytic processing of the amyloid precursor protein (APP) are important for the pathogenesis of Alzheimer's disease (AD). In the present study, we found that transgenic mice overexpressing wild-type human APP gene (hAPP/+) displayed a much higher expression of FAS, one of the death receptor subfamily. This FAS overexpression was significantly reduced in the cortex of mice overexpressing both wild-type hAPP gene and wild-type human superoxide dismutase-1 gene (hSOD-1). Moreover hSOD-1 transgenic expression was associated with an increase of Glial fibrillary acidic protein (GFAP) production. This study indicates that SOD-1 overexpression can inhibit FAS expression, which may be beneficial in AD.
淀粉样前体蛋白（APP）经蛋白水解加工产生的肽段对阿尔茨海默病（AD）的发病机制至关重要。在本研究中，我们发现过表达野生型人类APP基因（hAPP/+）的转基因小鼠死亡受体亚家族之一FAS的表达水平要高得多。在同时过表达野生型hAPP基因和野生型人类超氧化物歧化酶-1基因（hSOD-1）的小鼠皮层中，这种FAS的过表达显著降低。此外，hSOD-1转基因表达与胶质纤维酸性蛋白（GFAP）产生的增加有关。本研究表明，SOD-1过表达可抑制FAS表达，这可能对AD有益。
