The aggregation of intrinsically disordered proteins is a hallmark of neurodegenerative diseases, such as Alzheimer's, Parkinson's and Huntington's disease. Although we currently have a good molecular level understanding on how protein aggregation occurs in vitro, the details of its self-assembly in live cells are still mainly unknown. During the last ten years, we have witnessed the rapid development of advanced imaging techniques, especially super-resolution and fluorescence lifetime-based microscopy, in different areas of cell biology. These methods have been revolutionising our understanding of how proteins aggregate, providing unprecedented high spatial-temporal resolution which permits us to capture the kinetics of aggregate seeding and expansion, the motion and distribution of individual aggregates within the cells, and its structural change. In this article, we will review the study of in situ protein aggregation using advanced imaging techniques, with the focus on protein aggregate structure and its assembly dynamics.

中文翻译：

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原位蛋白质聚集的高级荧光成像。

本质上失调的蛋白质的聚集是神经退行性疾病的标志，例如阿尔茨海默氏病，帕金森氏病和亨廷顿氏病。尽管我们目前对分子在体外如何发生蛋白聚集具有很好的分子水平的了解，但在活细胞中其自组装的细节仍然主要未知。在过去的十年中，我们目睹了高级成像技术在细胞生物学不同领域的飞速发展，尤其是超分辨率和基于荧光寿命的显微镜。这些方法已经彻底改变了我们对蛋白质如何聚集的理解，提供了空前的高时空分辨率，使我们能够捕获聚集体播种和扩展的动力学，细胞内单个聚集体的运动和分布，及其结构变化。在本文中，我们将回顾使用先进的成像技术进行原位蛋白质聚集的研究，重点是蛋白质聚集结构及其组装动力学。