Alzheimer's disease (AD) is a neuronal dementia with progressive memory loss. Amyloid-beta (Aβ) peptides has major effect in the neurodegenerative disorder, which are thought to promote mitochondrial dysfunction in AD brains. Anti-AD drugs acting upon the brain are generally difficult to develop, often cause serious side effects or lack therapeutic efficacy. Numerous studies have shown the beneficial therapeutic applications of gold nanoparticles (AuNPs), including for neuroprotective events and AD. The aim of this study is to understand how AuNPs could exert their neuroprotective role in AD, for which cell model have chosen human neural stem cells (hNSCs) as the experimental tool. We hypothesize AuNPs protect against Aβ-induced cellular impairment and mitochondrial dysfunction in hNSCs. Here, we show AuNPs increase the survival of hNSCs treated with Aβ via downregulation of caspase 3 and 9 activities. Moreover, AuNPs abrogated the Aβ-mediated decrease neuroprotective (CREB and Bcl-2) and mitochondrial (PGC1α, NRF-1 and Tfam) gene expressions in treated hNSCs. Importantly, co-treatment with AuNPs significantly rescued hNSCs from Aβ-mediated mitochondrial function and morphology. AuNPs also significantly normalizes the immunostaining of mitochondrial marker and mass in differentiated hNSCs with Aβ. The effects may be exerted by the AuNPs, as supported by its protective reversal of Aβ-induced cellular impairment and mitochondrial dysfunction in hNSCs. In fact, the results presented extend our understanding of the mechanisms through which AuNPs could exert their neuroprotective role in hNSCs treated with Aβ.

中文翻译：

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在神经干细胞对淀粉样β诱导的线粒体功能障碍的纳米金神经保护。

阿尔茨海默氏病（AD）是具有进行性记忆丧失的神经元痴呆。淀粉样蛋白（Aβ）肽在神经退行性疾病中具有重要作用，据认为该疾病可促进AD脑线粒体功能障碍。作用于大脑的抗AD药物通常难以开发，经常引起严重的副作用或缺乏治疗功效。大量研究表明，金纳米颗粒（AuNPs）的有益治疗应用包括神经保护作用和AD。这项研究的目的是了解AuNPs如何在AD中发挥其神经保护作用，为此，细胞模型选择了人类神经干细胞（hNSCs）作为实验工具。我们假设AuNPs可以抵抗hNSCs中Aβ诱导的细胞损伤和线粒体功能障碍。这里，我们显示AuNPs通过下调caspase 3和9活性来增加用Aβ处理的hNSCs的存活率。此外，AuNPs消除了治疗的hNSCs中Aβ介导的神经保护性降低（CREB和Bcl-2）和线粒体（PGC1α，NRF-1和Tfam）基因表达的降低。重要的是，与AuNPs共同治疗可将hNSCs从Aβ介导的线粒体功能和形态中拯救出来。AuNPs还显着标准化了Aβ分化的hNSCs中线粒体标记物和质量的免疫染色。这种作用可能是由于AuNPs的保护性逆转所致，因为它可以逆转hNSCs中Aβ诱导的细胞损伤和线粒体功能障碍。实际上，提出的结果扩展了我们对AuNPs可以在Aβ处理的hNSCs中发挥神经保护作用的机制的理解。