title: Evaluation of the effects of amyloid β aggregation from seaweed extracts by a microliter-scale high-throughput screening system with a quantum dot nanoprobe.
abstract: Inhibitors of amyloid β (Aβ) aggregation have the potential to serve as lead compounds for anti-Alzheimer's disease (AD) agents because Aβ aggregation is a key step in AD pathogenesis. Recently, we developed a novel microliter-scale high-throughput screening (MSHTS) system for Aβ aggregation inhibitors that applied fluorescence microscopic analysis with quantum dot nanoprobes, and attempted to comprehensively screen the inhibitors from spices using this system (Ishigaki et al., PLoS One, 8, e72992, 2013). In this study, we tried to evaluate the inhibitory activities of 11 seaweed extracts on Aβ aggregation using the MSHTS system. The half-maximal effective concentration (EC50) of the ethanolic extracts from all seaweeds exceeded 4.9 mg/ml, indicating that the extracts inhibit Aβ aggregation although this activity was significantly lower than that displayed by members of the Lamiaceae, a family of herbal spices that showed highest activity among 52 spices tested in our 2013 study. On the other hand, the EC50 of boiling water extracts was 0.013-0.42 mg/ml which was comparable with the EC50 of the extracts from the Lamiaceae family. These results suggest that the extraction efficiency of the inhibitors by boiling water extraction was higher than that by ethanolic extraction. Moreover, analysis of fluorescence micrographs, which were obtained from the MSHTS system, revealed that the morphology of the Aβ aggregates coincubated with boiling water extracts differed from control aggregates, suggesting that the MSHTS system is also useful for screening substances that affect the morphology of aggregates.
authors.affiliation: Department of Applied Sciences, Muroran Institute of Technology, 27-1 Mizumoto-cho, Muroran, Hokkaido 050-8585, Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Ogara
authors.affiliation: Department of Applied Sciences, Muroran Institute of Technology, 27-1 Mizumoto-cho, Muroran, Hokkaido 050-8585, Japan.
authors.forename: Tomohito
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Laboratory of Marine Industrial Science and Technology, Faculty of Fisheries Sciences, Hokkaido University, Hakodate, Hokkaido 041-8611, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Yasui
authors.affiliation: Department of Applied Sciences, Muroran Institute of Technology, 27-1 Mizumoto-cho, Muroran, Hokkaido 050-8585, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Uwai
authors.affiliation: Department of Applied Sciences, Muroran Institute of Technology, 27-1 Mizumoto-cho, Muroran, Hokkaido 050-8585, Japan. Electronic address: tokuraku@mmm.muroran-it.ac.jp.
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Tokuraku
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D057166:High-Throughput Screening Assays / Q000379:methods*; D015335:Molecular Probes; D066263:Protein Aggregation, Pathological / Q000188:drug therapy; D045663:Quantum Dots; D012624:Seaweed / Q000737:chemistry*; D014020:Tissue Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D015335:Molecular Probes; D014020:Tissue Extracts
keywords: Alzheimer's disease; Amyloid; High-throughput screening; Quantum dots; Seaweed