Altered expression of Notch1 in Alzheimer's disease
Altered expression of Notch1 in Alzheimer's disease
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DOI：
10.1371/journal.pone.0224941
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发表时间：
2019-11-26
期刊：
影响因子：
3.7
通讯作者：
Koh, Young Ho
中科院分区：
文献类型：
--
作者：
Cho, Sun-Jung;Yun, Sang-Moon;Koh, Young Ho
Notch 信号传导是一种进化上保守的途径，通过 Notch 家族受体与其同源配体的结合来调节细胞间相互作用。 Notch信号传导在血管发育和血管生成中具有重要作用。最近的研究报告称，Notch 可能与阿尔茨海默病 (AD) 的病理生理学有关。我们测量了 72 名痴呆患者（平均年龄 75.1 岁）、89 名遗忘性轻度认知障碍（MCI）受试者（平均年龄 73.72 岁）和 150 名认知正常对照者（平均年龄 72.34 岁）血浆样本中可溶性 Notch1 (sNotch1) 的水平。与健康对照组相比，痴呆症患者的 sNotch1 血浆水平降低了 25.27%。然而，经过β淀粉样蛋白处理后，人脑微血管内皮细胞（HBMEC）中Notch1蛋白的水平显着增加。此外，与正常对照相比，AD 患者的 HBMEC 和 iPSC 衍生神经元细胞中的 Notch1 mRNA 水平显着增加。这些结果表明 Notch1 表达的改变可能与阿尔茨海默病的风险有关。
Notch signaling is an evolutionarily conserved pathway that regulates cell-cell interactions through binding of Notch family receptors to their cognate ligands. Notch signaling has an essential role in vascular development and angiogenesis. Recent studies have reported that Notch may be implicated in Alzheimer's disease (AD) pathophysiology. We measured the levels of soluble Notch1 (sNotch1) in the plasma samples from 72 dementia patients (average age 75.1 y), 89 subjects with amnestic mild cognitive impairment (MCI) (average age 73.72 y), and 150 cognitively normal controls (average age 72.34 y). Plasma levels of sNotch1 were 25.27% lower in dementia patients as compared to healthy control subjects. However, the level of Notch1 protein was significantly increased in human brain microvascular endothelial cells (HBMECs) after amyloid-beta treatment. Also, Notch1 mRNA level was significantly increased in HBMECs and iPSC-derived neuronal cells from AD patient compared to normal control. These results indicate that altered expression of Notch1 might be associated with the risk of Alzheimer's disease.