Real-Time 3D Imaging and Inhibition Analysis of Various Amyloid Aggregations Using Quantum Dots
Real-Time 3D Imaging and Inhibition Analysis of Various Amyloid Aggregations Using Quantum Dots
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DOI：
10.3390/ijms21061978
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发表时间：
2020-03-01
影响因子：
5.6
通讯作者：
Tokuraku, Kiyotaka
中科院分区：
文献类型：
--
作者：
Lin, Xuguang;Galaqin, Nuomin;Tokuraku, Kiyotaka
淀粉样变性是指蛋白质的聚集，其积累并作为淀粉样纤维沉积到斑块中。当这些在器官中被检测到时，它们是阿尔茨海默病，帕金森病和其他相关疾病的主要标志。最近的医学进展表明，许多前体和蛋白质可以诱导淀粉样变性，尽管淀粉样蛋白聚集的机制以及这些蛋白质与淀粉样变性的关系仍不清楚。在这项研究中，我们报告了实时3D成像和抑制分析淀粉样蛋白β（A β），tau和α-突触核蛋白聚集利用量子点（QD）和淀粉样蛋白聚集体之间的亲和力。我们成功地可视化这些淀粉样蛋白聚集在实时荧光显微镜和共聚焦显微镜简单地通过添加市售的QD。透射电子显微镜（TEM）观察显示QD颗粒与所有淀粉样纤维结合。QD的3D成像揭示了由不同淀粉样肽组成的淀粉样蛋白聚集体之间的差异，这些差异无法通过TEM检测到。我们还能够量化迷迭香酸对这些蛋白质的抑制活性，迷迭香酸对A β聚集具有高活性，来自荧光显微照片，作为半最大有效浓度。QD的这些成像技术可作为快速，简单和强大的工具来了解淀粉样变性和发现治疗药物。
Amyloidosis refers to aggregates of protein that accumulate and are deposited as amyloid fibrils into plaques. When these are detected in organs, they are the main hallmark of Alzheimer's disease, Parkinson's disease, and other related diseases. Recent medical advances have shown that many precursors and proteins can induce amyloidosis even though the mechanism of amyloid aggregation and the relationship of these proteins to amyloidosis remains mostly unclear. In this study, we report the real-time 3D-imaging and inhibition analysis of amyloid beta (A beta), tau, and alpha-synuclein aggregation utilizing the affinity between quantum dots (QD) and amyloid aggregates. We successfully visualized these amyloid aggregations in real-time using fluorescence microscopy and confocal microscopy simply by adding commercially available QD. The observation by transmission electron microscopy (TEM) showed that QD particles bound to all amyloid fibrils. The 3D-imaging with QD revealed differences between amyloid aggregates composed of different amyloid peptides that could not be detected by TEM. We were also able to quantify the inhibition activities of these proteins by rosmarinic acid, which has high activity for A beta aggregation, from fluorescence micrographs as half-maximal effective concentrations. These imaging techniques with QD serve as quick, easy, and powerful tools to understand amyloidosis and to discover drugs for therapies.