Alzheimer's disease-like alterations in peripheral cells from presenilin-1 transgenic mice
Alzheimer's disease-like alterations in peripheral cells from presenilin-1 transgenic mice
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DOI：
10.1006/nbdi.2000.0378
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发表时间：
2001-04-01
影响因子：
6.1
通讯作者：
Müller, WE
中科院分区：
文献类型：
--
作者：
Eckert, A;Schindowski, K;Müller, WE
许多早发性遗传性阿尔茨海默病 (AD) 病例是由早老蛋白-1 (PS1) 基因突变引起的。 PS1突变在细胞培养系统和转基因小鼠原代神经元中的表达增加了它们对细胞死亡的脆弱性。有趣的是，AD 患者的外周淋巴细胞也更容易发生细胞死亡。我们现在报告说，来自 PS1 突变转基因小鼠的淋巴细胞与来自 AD 患者的外周细胞和表达 PS1 突变的几种细胞培养系统表现出类似的对细胞死亡的超敏反应。突变体 PS1 的细胞死亡增强作用与活性氧产生的增加和钙调节的改变有关，但与线粒体细胞色素 c 的变化无关。我们的研究进一步强调了突变体PS1的致病作用，并可能为缩小使用突变体PS1转染的神经元细胞系、来自转基因动物的神经元和来自AD患者的外周细胞的研究之间的差距的新努力提供基础基础。 (C) 2001 年学术出版社。
Many cases of early-onset inherited Alzheimer's disease (AD) are caused by mutations in the presenilin-1 (PS1) gene. Expression of PS1 mutations in cell culture systems and in primary neurons from transgenic mice increases their vulnerability to cell death. Interestingly, enhanced vulnerability to cell death has also been demonstrated for peripheral lymphocytes from AD patients. We now report that lymphocytes from PS1 mutant transgenic mice show a similar hypersensitivity to cell death as do peripheral cells from AD patients and several cell culture systems expressing PS1 mutations. The cell death-enhancing action of mutant PS1 was associated with increased production of reactive oxygen species and altered calcium regulation, but not with changes of mitochondrial cytochrome c. Our study further emphasizes the pathogenic role of mutant PS1 and may provide the fundamental basis for new efforts to close the gap between studies using neuronal cell lines transfected with mutant PS1, neurons from transgenic animals, and peripheral cells from AD patients. (C) 2001 Academic Press.