Issue 18, 2024

Accelerating protein aggregation and amyloid fibrillation for rapid inhibitor screening

Abstract

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.

Graphical abstract: Accelerating protein aggregation and amyloid fibrillation for rapid inhibitor screening

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Article information

Article type
Edge Article
Submitted
19 Jan 2024
Accepted
04 Apr 2024
First published
04 Apr 2024
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2024,15, 6853-6859

Accelerating protein aggregation and amyloid fibrillation for rapid inhibitor screening

J. Fan, L. Liang, X. Zhou and Z. Ouyang, Chem. Sci., 2024, 15, 6853 DOI: 10.1039/D4SC00437J

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