SOD1 rescues cerebral endothelial dysfunction in mice overexpressing amyloid precursor protein
SOD1 rescues cerebral endothelial dysfunction in mice overexpressing amyloid precursor protein
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DOI：
10.1038/5715
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发表时间：
1999-02-01
影响因子：
25
通讯作者：
Carlson, GA
中科院分区：
文献类型：
--
作者：
Iadecola, C;Zhang, FY;Carlson, GA
β-淀粉样蛋白前体蛋白 (APP) 的蛋白水解加工衍生的肽，包括淀粉样蛋白-β 肽，对于阿尔茨海默氏痴呆的发病机制很重要。我们发现过度表达 APP 的转基因小鼠对新皮质微循环的内皮依赖性调节具有严重的选择性损伤。在同时表达 APP 和超氧化物歧化酶 1 (SOD1) 的转基因小鼠中或在将 SOD 局部应用于大脑皮层的 APP 转基因小鼠中，没有发现这种内皮功能障碍。 APP 加工衍生的肽对脑血管的影响可能会导致阿尔茨海默氏痴呆症中脑血流的改变和神经元功能障碍。
Peptides derived from proteolytic processing of the beta-amyloid precursor protein (APP), including the amyloid-beta peptide, are important for the pathogenesis of Alzheimer's dementia. We found that transgenic mice overexpressing APP have a profound and selective impairment in endothelium-dependent regulation of the neocortical microcirculation. Such endothelial dysfunction was not found in transgenic mice expressing both APP and superoxide dismutase-1 (SOD1) or in APP transgenics in which SOD was topically applied to the cerebral cortex. These cerebrovascular effects of peptides derived from APP processing may contribute to the alterations in cerebral blood flow and to neuronal dysfunction in Alzheimer's dementia.