An automated microliter-scale high-throughput screening system (MSHTS) for real-time monitoring of protein aggregation using quantum-dot nanoprobes

Scientific Reports
Rina SasakiKiyotaka Tokuraku

Abstract

Protein aggregation is the principal component of numerous protein misfolding pathologies termed proteinopathies, such as Alzheimer's disease, Parkinson's disease, prion disease, and AA amyloidosis with unmet treatment needs. Protein aggregation inhibitors have great potential for the prevention and treatment of proteinopathies. Here we report the development of an automated real-time microliter-scale high throughput screening (MSHTS) system for amyloid aggregation inhibitors using quantum-dot nanoprobes. Screening 504 crude extracts and 134 low molecular weight aromatic compounds revealed the relationship of amyloid-β (Aβ) aggregation inhibitory activities of plant extracts using a plant-based classification. Within the eudicots, rosids, Geraniales and Myrtales showed higher activity. Screening low molecular weight aromatic compounds demonstrated that the structure of tropolone endows it with potential Aβ aggregation inhibitory activity. The activity of the most active tropolone derivative was higher than that of rosmarinic acid. MSHTS also identified three chaperone molecules as tau aggregation inhibitors. These results demonstrate that our automated MSHTS system is a novel and robust tool that can be adapted to a wide range ...Continue Reading

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Citations

Mar 19, 2020·International Journal of Molecular Sciences·Xuguang LinKiyotaka Tokuraku
Aug 18, 2020·Journal of Clinical Biochemistry and Nutrition·Miki Hiemori-Kondo
Sep 11, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Hadya Virupaksha DeepakKenji Monde
Jun 18, 2020·Scientific Reports·Masahiro KuraganoKiyotaka Tokuraku
Nov 2, 2019·Chemical Reviews·Amir AliyanAngel A Martí

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Methods Mentioned

BETA
Fluorescence
confocal microscopy

Software Mentioned

MSHTS
JANUS G3
XYZ

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