Gharb Masoumeh, Nouralishahi Amideddin, Riazi Ali, Riazi Gholamhossein
Institute of Biochemistry and Biophysics, University of Tehran, Tehran 14176-14335, Iran.
Caspian Factually of Engineering, University of Tehran, Rezvanshahr 4386191836, Gilan Iran.
ACS Omega. 2022 Aug 18;7(34):30347-30358. doi: 10.1021/acsomega.2c03616. eCollection 2022 Aug 30.
A potential therapeutic strategy to inhibit tau protein aggregation in neurons has substantial effects on preventing or controlling Alzheimer's disease (AD). In this work, we designed a covalent and noncovalent conjugation of β-boswellic acid (BA) to gold nanoparticles (GNPs). We provided the opportunity to investigate the effect of the surface composition of BA-GNPs on the aggregation of the tau protein 1N/4R isoform in vitro. HR-TEM and FESEM micrographs revealed that GNPs were spherical and uniform, smaller than 25 nm. According to UV-visible and FTIR data, BA was successfully conjugated to GNPs. The finding illustrates the effect of the surface charge, size, and hydrophobicity of BA-GNPs on the kinetics of tau protein aggregation. The size and surface area of U-G-BA demonstrated that inhibited tau aggregation more effectively than covalently linked BA. The proposed method for preventing tau aggregation was monomer reduction. At the same time, a chaperone-like feature of GNP-BA while sustaining a tau native structure prevented the additional formation of fibrils. Overall, this study provides insight into the interaction of GNP-BAs with a monomer of tau protein and may suggest novel future therapies for AD.
一种抑制神经元中tau蛋白聚集的潜在治疗策略对预防或控制阿尔茨海默病（AD）具有重大影响。在这项工作中，我们设计了β-乳香酸（BA）与金纳米颗粒（GNP）的共价和非共价共轭。我们提供了一个机会来研究BA-GNP的表面组成对tau蛋白1N/4R异构体在体外聚集的影响。高分辨透射电子显微镜（HR-TEM）和场发射扫描电子显微镜（FESEM）显微照片显示，GNP呈球形且均匀，小于25nm。根据紫外可见光谱和傅里叶变换红外光谱（FTIR）数据，BA成功地与GNP共轭。这一发现说明了BA-GNP的表面电荷、大小和疏水性对tau蛋白聚集动力学的影响。未共价结合BA的GNP-BA的大小和表面积表明，其比共价连接的BA更有效地抑制tau聚集。所提出的预防tau聚集的方法是减少单体。同时，GNP-BA的伴侣样特征在维持tau天然结构的同时防止了原纤维的额外形成。总的来说，这项研究深入了解了GNP-BA与tau蛋白单体的相互作用，并可能为AD提出新的未来治疗方法。
