Department of Neurosurgery, Kermanshah University of Medical Sciences, Imam Reza Hospital, 67158-47141 Kermanshah, Iran.
Department of Mechanical Engineering, University of British Columbia, 2054-6250 Applied Science Lane, Vancouver, British Columbia V6T1Z4, Canada.
ACS Appl Bio Mater. 2021 Aug 16;4(8):6073-6083. doi: 10.1021/acsabm.1c00421. Epub 2021 Jul 26.
Carbon nanoparticles are becoming promising agents in treating Parkinson's disease (PD) by preventing the folding and aggregation of α-synuclein, i.e., amyloid formation. Herein, for the first time, highly tunable graphene and carbon nanotubes (CNTs) have been doped using biocompatible silicon atoms for preventing Parkinson's disease. In this study, the conformational changes induced by these nanoparticles, the compactness of nanoparticles, the number of hydrogen bonds, the stability of α-synuclein in the presence of nanoparticles, and the interaction energies between α-synuclein and nanoparticles were investigated using microsecond coarse-grained and all-molecular-atom simulations. Although the nanoparticles considered in this study could induce desirable changes in α-synuclein conformations, Si-graphene (silicon-doped graphene) demonstrated the best performance. Si-graphene showed the highest interaction energy with α-synuclein compared to other nanoparticles, induced the most hydrogen bonds, was the least compact, and showed the most unstable α-synuclein conformation, resulting in the highest capability to prevent the folding and aggregation of α-synuclein. Our results displayed that 2D hexagonal structures, such as graphene and Si-graphene, possess better performance than tubular structures in inducing conformational changes in the α-synuclein protein. Furthermore, it was observed that the doping of silicon in graphene and CNT results in better folding and aggregation of α-synuclein prevention. This molecular investigation offers a nanostructure method in PD treatment.
碳纳米粒子通过防止α-突触核蛋白（即淀粉样蛋白形成）的折叠和聚集，成为治疗帕金森病（PD）的有前途的药物。在此，首次使用生物相容性硅原子对高度可调谐的石墨烯和碳纳米管（CNT）进行掺杂，以预防帕金森病。在这项研究中，使用微秒粗粒化和全分子原子模拟研究了这些纳米粒子引起的构象变化、纳米粒子的紧凑性、氢键的数量、纳米粒子存在下α-突触核蛋白的稳定性以及α-突触核蛋白与纳米粒子之间的相互作用能。尽管本研究中考虑的纳米粒子可以诱导α-突触核蛋白构象的理想变化，但 Si-石墨烯（硅掺杂石墨烯）表现出最佳性能。与其他纳米粒子相比，Si-石墨烯与α-突触核蛋白具有最高的相互作用能，诱导了最多的氢键，最不紧凑，并且具有最不稳定的α-突触核蛋白构象，从而具有最高的防止α-突触核蛋白折叠和聚集的能力。我们的结果表明，二维六方结构，如石墨烯和 Si-石墨烯，在诱导α-突触核蛋白蛋白构象变化方面比管状结构具有更好的性能。此外，观察到在石墨烯和 CNT 中掺杂硅可以更好地预防α-突触核蛋白的折叠和聚集。这项分子研究为 PD 治疗提供了一种纳米结构方法。
