Neuroprotective effects of apigenin against inflammation, neuronal excitability and apoptosis in an induced pluripotent stem cell model of Alzheimer's disease.
Neuroprotective effects of apigenin against inflammation, neuronal excitability and apoptosis in an induced pluripotent stem cell model of Alzheimer's disease.
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DOI：
10.1038/srep31450
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发表时间：
2016-08-12
影响因子：
4.6
通讯作者：
Ooi L
中科院分区：
文献类型：
--
作者：
Balez R;Steiner N;Engel M;Muñoz SS;Lum JS;Wu Y;Wang D;Vallotton P;Sachdev P;O'Connor M;Sidhu K;Münch G;Ooi L
阿尔茨海默病（Alzheimer's disease，AD）是最常见的神经退行性疾病之一，但由于其发病机制复杂，目前的治疗方法尚不充分。植物多酚芹菜素已被证明在许多细胞和动物模型中具有抗炎和神经保护特性;然而，尚未在人类AD模型中进行全面评估。在这里，我们使用了人类诱导多能干细胞（iPSC）模型的家族性和散发性AD，除了健康对照，以评估芹菜素的神经保护活性。与对照神经元相比，iPSC衍生的AD神经元表现出过度兴奋的钙信号传导表型、升高的亚硝酸盐水平、增加的细胞毒性和凋亡、减少的神经突长度和增加的对来自活化的鼠小胶质细胞的炎性应激挑战的易感性。我们发现芹菜素具有有效的抗炎特性，能够通过促进炎症细胞中细胞因子和一氧化氮（NO）释放的全面下调来保护神经突和细胞活力。此外，我们表明芹菜素能够通过多种手段通过降低自发Ca 2+信号的频率和显著降低caspase-3/7介导的凋亡来保护iPSC衍生的AD神经元。这些数据证明了芹菜素在人类疾病模型中对AD发病机制的广泛神经保护作用。
Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative diseases, yet current therapeutic treatments are inadequate due to a complex disease pathogenesis. The plant polyphenol apigenin has been shown to have anti-inflammatory and neuroprotective properties in a number of cell and animal models; however a comprehensive assessment has not been performed in a human model of AD. Here we have used a human induced pluripotent stem cell (iPSC) model of familial and sporadic AD, in addition to healthy controls, to assess the neuroprotective activity of apigenin. The iPSC-derived AD neurons demonstrated a hyper-excitable calcium signalling phenotype, elevated levels of nitrite, increased cytotoxicity and apoptosis, reduced neurite length and increased susceptibility to inflammatory stress challenge from activated murine microglia, in comparison to control neurons. We identified that apigenin has potent anti-inflammatory properties with the ability to protect neurites and cell viability by promoting a global down-regulation of cytokine and nitric oxide (NO) release in inflammatory cells. In addition, we show that apigenin is able to protect iPSC-derived AD neurons via multiple means by reducing the frequency of spontaneous Ca2+ signals and significantly reducing caspase-3/7 mediated apoptosis. These data demonstrate the broad neuroprotective action of apigenin against AD pathogenesis in a human disease model.