School of Life Sciences, Jawaharlal Nehru University, New Delhi-110067, India.
ACS Chem Neurosci. 2020 Nov 18;11(22):3772-3785. doi: 10.1021/acschemneuro.0c00366. Epub 2020 Oct 30.
Parkinson's disease (PD) is the most common progressive neurodegenerative disease known to impart bradykinesia leading to diverse metabolic complications. Currently, scarcity of effective drug candidates against this long-term devastating disorder poses a big therapeutic challenge. Here, we have synthesized biocompatible, polycrystalline, and uniform piperine-coated gold nanoparticles (AuNPs) to specifically target paraquat-induced metabolic complications both in and SH-SY5Y cells. Our experimental evidence clearly revealed that AuNPs can effectively reverse paraquat-induced lethal effects in both and model systems of PD. AuNPs were found to suppress oxidative stress and mitochondrial dysfunction, leading to inhibition of apoptotic cell death in paraquat-treated flies. AuNPs were also found to protect SH-SY5Y cells against paraquat-induced toxicity at the cellular level preferably by maintaining mitochondrial membrane potential. Both experimental and computational data point to the possible influence of AuNPs in regulating the homeostasis of and which may turn out to be the key factors in reducing PD symptoms. The findings of this work may facilitate the development of piperine-based nanoformulations against PD.
帕金森病(PD)是最常见的进行性神经退行性疾病,已知其会导致运动迟缓,并引发多种代谢并发症。目前,针对这种长期破坏性疾病,缺乏有效的药物候选物,这是一个巨大的治疗挑战。在这里,我们合成了生物相容性的、多晶的、均匀的胡椒碱包覆的金纳米粒子(AuNPs),以专门针对百草枯诱导的代谢并发症,同时在 和 SH-SY5Y 细胞中进行了研究。我们的实验证据清楚地表明,AuNPs 可以有效地逆转 和 PD 模型系统中百草枯诱导的致命作用。AuNPs 被发现可以抑制氧化应激和线粒体功能障碍,从而抑制百草枯处理的果蝇中的细胞凋亡死亡。AuNPs 还被发现可以在细胞水平上保护 SH-SY5Y 细胞免受百草枯诱导的毒性,优选通过维持线粒体膜电位来实现。实验和计算数据都指向 AuNPs 可能在调节 和 的动态平衡方面发挥作用,这可能是减轻 PD 症状的关键因素。这项工作的结果可能有助于开发基于胡椒碱的纳米制剂来治疗 PD。