State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan 430070, China.
School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, Wuhan 430070, China.
Biomaterials. 2019 Feb;194:36-46. doi: 10.1016/j.biomaterials.2018.12.013. Epub 2018 Dec 13.
Drug discovery for Parkinson's disease (PD) is challenging. Here we report that gold nanoclusters (AuNCs) can serve as a novel candidate for the design of anti-PD drugs. With N-isobutyryl-l-cysteine (L-NIBC) protected AuNCs as an example, we show that AuNCs effectively prevent α-Synuclein (α-Syn) fibrillation in in vitro experiments. Cell experiments demonstrate good neuroprotective effects in PD cell models. More significantly, experiments of mouse PD model further show that AuNCs largely ameliorate the behavioral disorders of sick mice. In addition, immunohistochemical and western blot (WB) analyses indicate that AuNCs can significantly reverse dopaminergic (DA) neuron loss in substantia nigra and striatum of sick mice. This study opens up a novel avenue to develop anti-PD drugs and points a new direction for AuNCs in medicinal applications.
帕金森病(PD)的药物研发具有挑战性。在这里,我们报告金纳米簇(AuNCs)可以作为设计抗 PD 药物的新候选物。以 N-异丁酰-L-半胱氨酸(L-NIBC)保护的 AuNCs 为例,我们表明 AuNCs 可有效防止α-突触核蛋白(α-Syn)在体外实验中的纤颤。细胞实验表明,AuNCs 在 PD 细胞模型中具有良好的神经保护作用。更重要的是,小鼠 PD 模型实验进一步表明,AuNCs 可显著改善患病小鼠的行为障碍。此外,免疫组织化学和蛋白质印迹(WB)分析表明,AuNCs 可显著逆转患病小鼠黑质和纹状体中多巴胺能(DA)神经元的丢失。这项研究为开发抗 PD 药物开辟了新途径,并为 AuNCs 在药物应用方面指明了新方向。