Biancalana Matthew, Koide Shohei
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Biochim Biophys Acta. 2010 Jul;1804(7):1405-12. doi: 10.1016/j.bbapap.2010.04.001. Epub 2010 Apr 22.
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.
为检测、诊断并分析淀粉样纤维的动力学和结构特性，人们付出了巨大努力，由此产生了一套强大的淀粉样特异性分子探针工具包。自1959年首次被描述以来，荧光染料硫黄素-T（ThT）已成为体内外选择性染色和鉴定淀粉样纤维最广泛使用的“金标准”之一。与纤维结合后其荧光发射大幅增强，这使得ThT成为一种特别强大且便捷的工具。尽管它在临床和基础科学应用中广泛使用，但ThT识别不同类型淀粉样纤维的能力及其特征荧光的分子机制才刚刚开始得到阐明。在此，我们回顾了在原子分辨率下对ThT-纤维相互作用理解的最新进展。这些研究为淀粉样结构和纤维形成过程提供了重要见解，也为设计下一代淀粉样聚集诊断、抑制剂和治疗方法提供了指导。
