Neuroglobin Attenuates Beta Amyloid-Induced Apoptosis Through Inhibiting Caspases Activity by Activating PI3K/Akt Signaling Pathway
Neuroglobin Attenuates Beta Amyloid-Induced Apoptosis Through Inhibiting Caspases Activity by Activating PI3K/Akt Signaling Pathway
复制标题
Neuroglobin 通过激活 PI3K/Akt 信号通路抑制 Caspases 活性来减弱 β 淀粉样蛋白诱导的细胞凋亡
DOI：
10.1007/s12031-015-0645-z
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发表时间：
2016-01-01
影响因子：
3.1
通讯作者：
Zhang, Xiong
中科院分区：
文献类型：
--
作者：
Li, Yu;Dai, Yu-bing;Zhang, Xiong
淀粉样β蛋白(Aβ)的过度积聚和沉积被认为是阿尔茨海默病(AD)发病机制中的关键事件。神经细胞凋亡是阿尔茨海默病的特征之一，这可能是Aβ诱导神经元毒性的机制之一。脑红蛋白(NGB)是一种新发现的脊椎动物血红素蛋白，具有抗缺氧和淀粉样蛋白损伤引起的细胞死亡的神经保护功能。然而，到目前为止，脑红蛋白保护作用的确切机制还没有确定。为了探讨NGB可能的神经保护作用及其机制，本研究以转基因AD小鼠(APPswe/PSEN1dE9)和转pAPPsWE的SH-SY5Y细胞为研究对象。在体内，通过脑室注射pNgb过表达NGB可以减弱记忆、认知障碍和斑块生成。在pAPPsWE转染的SH-SY5Y细胞中，NGB不仅减少Aβ(42)的生成，而且通过Akt激活磷酸化抑制caspase-3、caspase-9的激活，从而减轻线粒体功能障碍和细胞凋亡，这一作用可被磷脂酰肌醇3-激酶抑制剂(LY294002)抑制。我们的数据表明NGB的抗凋亡作用可能对AD起到神经保护作用。
Excessive accumulation and deposition of amyloid-beta (A beta) has been considered as a pivotal event in the pathogenesis of Alzheimer's disease (AD). Neuronal apoptosis is one of the characteristics of AD, which is a possible mechanism underlying A beta-induced neuronal neurotoxicity. Neuroglobin (Ngb) is a newly discovered vertebrate heme protein that exhibits neuroprotective functions against cell death associated with hypoxic and amyloid insult. However, until now, the exact mechanism of neuroglobin's protective action has not been determined. To investigate the potential neuroprotective roles and mechanisms of Ngb, transgenic AD mice (APPswe/PSEN1dE9) and SH-SY5Y cells transfected with pAPPswe were enrolled into the study. In vivo, overexpression of Ngb via intracerebroventricular injection with pNgb attenuated memory, cognitive impairment, and plaque generations. In pAPPswe transfected SH-SY5Y cells, Ngb not only decreased the generation of A beta(42), but also attenuated mitochondrial dysfunction and apoptosis through suppressing the activation of caspase-3, caspase-9 by Akt activating phosphorylation, which were restrained by phosphatidylinositol 3-kinase inhibitor (LY294002). Our data indicate the anti-apoptotic property of Ngb may play a neuroprotective role against AD.