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

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...

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Bibliographic Details
Published in:Scientific reports 2019-02, Vol.9 (1), p.2587-2587, Article 2587
Main Authors: Sasaki, Rina, Tainaka, Reina, Ando, Yuichi, Hashi, Yurika, Deepak, Hadya V., Suga, Yoshiko, Murai, Yuta, Anetai, Masaki, Monde, Kenji, Ohta, Kiminori, Ito, Ikuko, Kikuchi, Haruhisa, Oshima, Yoshiteru, Endo, Yasuyuki, Nakao, Hitomi, Sakono, Masafumi, Uwai, Koji, Tokuraku, Kiyotaka
Format: Article
Language:English
Subjects:
631/154/1435/2163
631/1647/2163
631/378/1689/1283
Amyloid
Amyloidosis
Aromatic compounds
Automation
High-throughput screening
Humanities and Social Sciences
Inhibitors
Molecular weight
multidisciplinary
Parkinson's disease
Plant extracts
Protein folding
Protein interaction
Proteins
Rosmarinic acid
Science
Science (multidisciplinary)
Tau protein
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Summary: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 of compounds and aggregation-prone polypeptides.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-019-38958-0