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Redox Biol :NOX2缺乏对神经前体细胞池的影响

2017-06-15 Emma MedSci原创

CGD(慢性肉芽肿性疾病)是一种少见的先天性疾病,其特征为反复细菌和真菌感染。在慢性肉芽肿病(CGD)患者中缺乏产生ROS的NOX2(NADPH氧化酶2),主要表现为免疫缺陷,与认知下降也密切相关。

CGD(慢性肉芽肿性疾病)是一种少见的先天性疾病,其特征为反复细菌和真菌感染。在慢性肉芽肿病(CGD)患者中缺乏产生ROS的NOX2(NADPH氧化酶2),主要表现为免疫缺陷,与认知下降也密切相关。

发表于Redox Biology的一篇文章中,研究人员调查了NOX酶对成年鼠脑以及源自iPSC(人诱导多能干细胞)的神经细胞神经元稳态的影响,为小鼠和人类神经发生早期阶段NOX2的调节作用提供了新的证据,也为活性氧(ROS)参与调节干细胞和细胞分化提供了新的证据。

研究显示,在小鼠成年神经源性区域发现高水平的NOX2;在NOX2缺陷小鼠中,神经源性区域显示氧化还原修饰减少、神经元数减少,并且包括NES,BDNF和OTX2在内的神经分化相关基因表达减少。为了探究NOX2在人体外神经元发育中的作用,研究人员使用了来自健康受试者和CGD患者的iPSC,NOX2的表达在未分化的iPSC中较低,神经诱导后上调,在神经元分化过程中消失。CGD-iPSC中NOX2缺乏导致体外神经诱导异常,神经祖细胞标志物(NES,BDNF,OTX2,NRSF / REST)的表达减少,以及成熟神经元生成减少。NOX2缺陷型iPSC中载体介导的NOX2表达能够缓解神经发生的不利情况。

原始出处:
Nayernia, Zeynab, et al. Decreased neural precursor cell pool in NADPH oxidase 2-deficiency: from mouse brain to neural differentiation of patient derived iPSC. Redox Biol. 2017 Apr 24;13:82-93. doi: 10.1016/j.redox.2017.04.026.


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