The size-effect of gold nanoparticles and nanoclusters in the inhibition of amyloid-β fibrillation
The size-effect of gold nanoparticles and nanoclusters in the inhibition of amyloid-β fibrillation
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金纳米粒子和纳米团簇在抑制淀粉样蛋白-β 纤维颤动中的尺寸效应
DOI：
10.1039/c7nr00699c
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发表时间：
2017-03-28
期刊：
影响因子：
6.7
通讯作者：
Sun, Taolei
中科院分区：
文献类型：
--
作者：
Gao, Guanbin;Zhang, Mingxi;Sun, Taolei
阿尔茨海默病（AD）的一个重要病理特征是β淀粉样蛋白（A β）斑块在脑中的沉积以及与之相关的突触功能障碍和神经变性。因此，期望开发抑制A β纤维化的化合物或药物来开发针对AD的新的治疗策略。常规策略通常需要对其分子结构进行精心设计。在这里，我们报告了金纳米粒子（AuNPs）和纳米簇（AuNCs）在抑制蛋白质淀粉样变性中的尺寸效应。使用L-谷胱甘肽稳定的金纳米粒子与不同大小的金纳米粒子为例，我们表明，大金纳米粒子加速A β纤维化，而小金纳米粒子显着抑制这一过程。更有趣的是，具有较小尺寸的AuNC可以完全抑制淀粉样变性。动态光散射（DLS）实验表明，AuNCs可以有效地防止A β肽聚集成较大的寡聚体（例如胶束），从而避免成核形成原纤维。这对于开发新型AD疗法至关重要，因为寡聚体是A β毒性的主要来源。这项工作提出了一种新的策略来设计抗淀粉样变性药物，这也提供了有趣的见解，从一个新的角度来了解生物纳米结构如何在体内参与A β纤维化。
A significant pathological signature of Alzheimer's disease (AD) is the deposition of amyloid-beta (A beta) plaques in the brain and the synaptic dysfunction and neurodegeneration associated with it. Compounds or drugs that inhibit A beta fibrillation are thus desirable to develop novel therapeutic strategies against AD. Conventional strategies usually require an elaborate design of their molecular structures. Here we report the size-effect of gold nanoparticles (AuNPs) and nanoclusters (AuNCs) in the inhibition of protein amyloidosis. Using L-glutathione stabilized AuNPs with different sizes and AuNCs as examples, we show that large AuNPs accelerate A beta fibrillation, whereas small AuNPs significantly suppress this process. More interestingly, AuNCs with smaller sizes can completely inhibit amyloidosis. Dynamic light scattering (DLS) experiments show that AuNCs can efficiently prevent A beta peptides from aggregation to larger oligomers (e.g. micelles) and thus avoid nucleation to form fibrils. This is crucially important for developing novel AD therapies because oligomers are the main source of A beta toxicity. This work presents a novel strategy to design anti-amyloidosis drugs, which also provides interesting insights to understand how biological nanostructures participate in vivo in A beta fibrillation from a new perspective.