Molecular mechanism of Thioflavin-T binding to amyloid fibrils.

Molecular mechanism of Thioflavin-T binding to amyloid fibrils.
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DOI:
10.1016/j.bbapap.2010.04.001
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发表时间:
2010-07
期刊:
Biochimica et biophysica acta
影响因子:
--
通讯作者:
Koide S
Koide S
中科院分区:
其他
文献类型:
--
作者:
Biancalana M;Koide S

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在检测、诊断和分析淀粉样蛋白原纤维的动力学和结构特性方面的努力已经产生了一个强大的淀粉样蛋白特异性分子探针工具包。自1959年首次描述以来,荧光染料硫黄素- t (ThT)已成为体内和体外选择性染色和鉴定淀粉样蛋白原纤维最广泛使用的“金标准”之一。与原纤维结合后其荧光发射的大幅增强使ThT成为一种特别强大和方便的工具。尽管ThT在临床和基础科学应用中广泛使用,但其识别不同类型淀粉样蛋白原纤维的能力和染料特征荧光的分子机制才刚刚开始阐明。在这里,我们回顾了在原子分辨率上对t -纤维相互作用的理解的最新进展。这些研究对淀粉样蛋白结构和原纤维形成过程产生了重要的见解,它们也为设计下一代淀粉样蛋白组装诊断、抑制剂和治疗方法提供了指导。
Intense efforts to detect, diagnose, and analyze the kinetic and structural properties of amyloid fibrils have generated a powerful toolkit of amyloid-specific molecular probes. Since its first description in 1959, the fluorescent dye Thioflavin-T (ThT) has become among the most widely used “gold standards” for selectively staining and identifying amyloid fibrils both in vivo and in vitro. The large enhancement of its fluorescence emission upon binding to fibrils makes ThT a particularly powerful and convenient tool. Despite its widespread use in clinical and basic science applications, the molecular mechanism for the ability of ThT to recognize diverse types of amyloid fibrils and for the dye’s characteristic fluorescence has only begun to be elucidated. Here, we review recent progress in the understanding of ThT-fibril interactions at an atomic resolution. These studies have yielded important insights into amyloid structures and the processes of fibril formation, and they also offer guidance for designing the next generation of amyloid assembly diagnostics, inhibitors, and therapeutics.
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