An automated microliter-scale high-throughput screening system (MSHTS) for real-time monitoring of protein aggregation using quantum-dot nanoprobes
| Autor: | Hitomi Nakao, Kiyotaka Tokuraku, Yoshiteru Oshima, Rina Sasaki, Masafumi Sakono, Hadya Virupaksha Deepak, Reina Tainaka, Yuichi Ando, Kiminori Ohta, Haruhisa Kikuchi, Koji Uwai, Masaki Anetai, Yasuyuki Endo, Kenji Monde, Yuta Murai, Yoshiko Suga, Ikuko Ito, Yurika Hashi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
High-throughput screening lcsh:Medicine Amyloidogenic Proteins Protein aggregation Amyloid Neuropathies Protein Aggregation Pathological Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine AA amyloidosis Drug Discovery Quantum Dots medicine Humans lcsh:Science Multidisciplinary biology Plant Extracts Rosmarinic acid lcsh:R Neurodegenerative Diseases medicine.disease Tropolone High-Throughput Screening Assays 030104 developmental biology chemistry Biochemistry Chaperone (protein) Amyloid aggregation biology.protein lcsh:Q Protein folding 030217 neurology & neurosurgery |
| Zdroj: | Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-9 (2019) |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|