Liang Hongli, Wang Bing, Wang Hailong, Yu Miao, Zheng Lingna, Wang Meng, Zhang Aiping, Feng Weiyue
Department of Pharmacy, Shanxi Medical University, Taiyuan, 030001, P. R. China.
Chinese Academy of Sciences Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049, P. R. China.
J Nanosci Nanotechnol. 2018 May 1;18(5):3087-3094. doi: 10.1166/jnn.2018.14662.
Amyloid fibrillation has been implicated in many neurodegenerations, dialysis-related amyloidosis, type II diabetes and more than 30 other amyloid-related diseases. Nanomaterials as potential inhibitors of amyloid fibrillation have attracted increasing interests. In the present study, the effects of gold nanorods (AuNRs) and nanoparticles (AuNPs) on amyloid fibrillation were investigated using hen egg white lysozyme (HEWL) as a model system. Our results indicated that AuNRs and AuNPs, especially AuNRs, present significant inhibitory effects on HEWL amyloid fibril formation during all the kinetic processes, from nucleation to elongation and equilibration stages. The stronger adsorption capacity of HEWL on AuNRs surface is the key mechanism of inhibition of HEWL amyloid fibrillation. Furthermore, AuNRs lead to more stable α-helix conformation and hydrophobic microenvironment of aromatic side groups in HEWL molecules, which facilitate the system to form small amorphous aggregates rather than oligomer, profibril or mature fibril.
淀粉样蛋白纤维化与许多神经退行性疾病、透析相关淀粉样变性、II型糖尿病以及30多种其他淀粉样蛋白相关疾病有关。纳米材料作为淀粉样蛋白纤维化的潜在抑制剂已引起越来越多的关注。在本研究中,以蛋清溶菌酶(HEWL)为模型系统,研究了金纳米棒(AuNRs)和纳米颗粒(AuNPs)对淀粉样蛋白纤维化的影响。我们的结果表明,AuNRs和AuNPs,尤其是AuNRs,在从成核到伸长和平衡阶段的所有动力学过程中,对HEWL淀粉样纤维形成均呈现出显著的抑制作用。HEWL在AuNRs表面更强的吸附能力是抑制HEWL淀粉样蛋白纤维化的关键机制。此外,AuNRs导致HEWL分子中更稳定的α-螺旋构象和芳香族侧基的疏水微环境,这有利于系统形成小的无定形聚集体,而不是寡聚体、前纤维或成熟纤维。