Amyloids are a broad class of proteins and peptides that can misfold and assemble into long unbranched fibrils with a cross-β conformation. These misfolding and aggregation events are associated with the onset of a variety of human diseases, among them, Alzheimer's disease, Parkinson's disease, and Huntington disease. Our understanding of amyloids has been greatly supported by fluorescent molecular probes, such as thioflavin-T, which shows an increase in fluorescence emission upon binding to fibrillar aggregates. Since the first application of thioflavin-T in amyloid studies nearly 30 years ago, many probes have emerged exhibiting a variety of responses to amyloids, such as intensity changes, shifts in fluorescence maxima, and variations in lifetimes, among many others. These probes have shed light on a variety of topics including the kinetics of amyloid aggregation, the effectiveness of amyloid aggregation inhibitors, the elucidation of binding sites in amyloid structures, and the staining of amyloids aggregates in vitro, ex vivo, and in vivo. In this Review, we discuss the design, properties, and application of photoactive probes used to study amyloid aggregation, as well as the challenges faced by current probes and techniques, and the novel approaches that are emerging to address these challenges.

中文翻译：

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使用荧光探针询问淀粉样蛋白聚集体。

淀粉样蛋白是一类广泛的蛋白质和肽，它们可以错误折叠并组装成具有交叉β构象的长直链原纤维。这些错误折叠和聚集事件与多种人类疾病的发作有关，其中包括阿尔茨海默氏病，帕金森氏病和亨廷顿氏病。我们对淀粉样蛋白的理解得到了荧光分子探针（例如硫黄素-T）的大力支持，该探针在与原纤维聚集体结合后显示出荧光发射的增加。自将近30年前硫黄素-T在淀粉样蛋白研究中首次应用以来，已经出现了许多对淀粉样蛋白表现出多种反应的探针，例如强度变化，荧光最大值变化和寿命变化等。这些探针阐明了许多主题，包括淀粉样蛋白聚集的动力学，淀粉样蛋白聚集抑制剂的有效性，淀粉样蛋白结构中结合位点的阐明以及淀粉样蛋白聚集体的体外，离体和体内染色。在这篇综述中，我们讨论了用于研究淀粉样蛋白聚集的光敏探针的设计，性质和应用，以及当前探针和技术所面临的挑战，以及为应对这些挑战而出现的新颖方法。