Introduction: The study of abnormal aggregation of proteins in different tissues of the body has recently earned great attention from researchers in various fields of science. Concerning neurological diseases, for instance, the accumulation of amyloid fibrils can contribute to Parkinson’s disease, a progressively severe neurodegenerative disorder. The most prominent features of this disease are the degeneration of neurons in the substantia nigra and accumulation of α-synuclein aggregates, especially in the brainstem, spinal cord, and cortical areas. Dopamine replacement therapies and other medications have reduced motor impairment and had positive consequences on patients’ quality of life. However, if these medications are stopped, symptoms of the disease will recur even more severely. Therefore, the improvement of therapies targeting more basic mechanisms like prevention of amyloid formation seems to be critical. It has been shown that the interactions between monolayers like graphene and amyloids could prevent their fibrillation.
Methods: For the first time, the impact of four types of last-generation graphene-based nanostructures on the prevention of α-synuclein amyloid fibrillation was investigated in this study by using molecular dynamics simulation tools.
Results: Although all monolayers were shown to prevent amyloid fibrillation, nitrogen-doped graphene (N-Graphene) caused the most instability in the secondary structure of α-synuclein amyloids. Moreover, among the four monolayers, N-Graphene was shown to present the highest absolute value of interaction energy, the lowest contact level of amyloid particles, the highest number of hydrogen bonds between water and amyloid molecules, the highest instability caused in α-synuclein particles, and the most significant decrease in the compactness of α-synuclein protein.
Discussion: Ultimately, it was concluded that N-Graphene could be the most effective monolayer to disrupt amyloid fibrillation, and consequently, prevent the progression of Parkinson’s disease.

Keywords: α-synuclein, amyloid, graphene, Parkinson’s disease, molecular dynamics


中文翻译：

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基于石墨烯的纳米粒子作为帕金森病的潜在治疗选择：分子动力学研究

介绍：对身体不同组织中蛋白质异常聚集的研究最近引起了各个科学领域研究人员的极大关注。例如，关于神经系统疾病，淀粉样蛋白原纤维的积累会导致帕金森病，这是一种进行性严重的神经退行性疾病。这种疾病最突出的特征是黑质神经元的退化和α-突触核蛋白聚集体的积累，特别是在脑干、脊髓和皮质区域。多巴胺替代疗法和其他药物减少了运动障碍，并对患者的生活质量产生了积极影响。然而，如果停止使用这些药物，疾病的症状会更严重地复发。所以，改进针对更基本机制（如预防淀粉样蛋白形成）的疗法似乎至关重要。已经表明，石墨烯和淀粉样蛋白等单层之间的相互作用可以防止它们的原纤维化。
方法：本研究首次利用分子动力学模拟工具研究了四类最新一代石墨烯基纳米结构对预防α-突触核蛋白淀粉样蛋白纤颤的影响。
结果：尽管所有单层均显示可防止淀粉样蛋白原纤维化，但氮掺杂石墨烯 (N-Graphene) 导致 α-突触核蛋白淀粉样蛋白的二级结构最不稳定。此外，在四个单层中，N-石墨烯的相互作用能绝对值最高，淀粉样蛋白颗粒的接触水平最低，水和淀粉样蛋白分子之间的氢键数量最多，α-突触核蛋白引起的不稳定性最高颗粒，并且α-突触核蛋白的紧密度下降最显着。
讨论：最终得出结论，N-石墨烯可能是最有效的单层破坏淀粉样蛋白纤颤，从而防止帕金森病的进展。

关键词： α-突触核蛋白，淀粉样蛋白，石墨烯，帕金森病，分子动力学