Fan Jingjin, Liang Liwen, Zhou Xiaoyu, Ouyang Zheng
State Key Laboratory of Precision Measurement Technology and Instruments, Department of Precision Instrument, Tsinghua University Beijing 100084 China
Chem Sci. 2024 Apr 4;15(18):6853-6859. doi: 10.1039/d4sc00437j. eCollection 2024 May 8.
The accumulation and deposition of amyloid fibrils, also known as amyloidosis, in tissues and organs of patients has been found to be linked to numerous devastating neurodegenerative diseases. The aggregation of proteins to form amyloid fibrils, however, is a slow pathogenic process, and is a major issue for the evaluation of the effectiveness of inhibitors in new drug discovery and screening. Here, we used microdroplet reaction technology to accelerate the amyloid fibrillation process, monitored the process to shed light on the fundamental mechanism of amyloid self-assembly, and demonstrated the value of the technology in the rapid screening of potential inhibitor drugs. Proteins in microdroplets accelerated to form fibrils in milliseconds, enabling an entire cycle of inhibitor screening for Aβ40 within 3 minutes. The technology would be of broad interest to drug discovery and therapeutic design to develop treatments for diseases associated with protein aggregation and fibrillation.
淀粉样纤维的积累和沉积，即淀粉样变性，在患者的组织和器官中被发现与许多毁灭性的神经退行性疾病有关。然而，蛋白质聚集成淀粉样纤维是一个缓慢的致病过程，并且是新药发现和筛选中抑制剂有效性评估的主要问题。在这里，我们使用微滴反应技术加速淀粉样纤维化过程，监测该过程以揭示淀粉样自组装的基本机制，并证明了该技术在快速筛选潜在抑制剂药物方面的价值。微滴中的蛋白质在几毫秒内加速形成纤维，从而能够在3分钟内完成针对Aβ40的抑制剂筛选的整个循环。该技术对于药物发现和治疗设计具有广泛的意义，可用于开发针对与蛋白质聚集和纤维化相关疾病的治疗方法。
