Screening of amyloid aggregation inhibitors using quantum dot nanoprobe and elucidation of the inhibition mechanism
Project/Area Number |
16H03288
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Chemical biology
|
Research Institution | Muroran Institute of Technology |
Principal Investigator |
|
Co-Investigator(Kenkyū-buntansha) |
中村 宗一郎 信州大学, 役員等, 理事 (00105305)
橋 友理香 山野美容芸術短期大学, その他部局等, 講師 (40756962)
上井 幸司 室蘭工業大学, 大学院工学研究科, 准教授 (80347905)
|
Project Period (FY) |
2016-04-01 – 2019-03-31
|
Project Status |
Completed (Fiscal Year 2018)
|
Budget Amount *help |
¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000)
Fiscal Year 2018: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2017: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2016: ¥10,790,000 (Direct Cost: ¥8,300,000、Indirect Cost: ¥2,490,000)
|
Keywords | アミロイド / 凝集阻害 / 量子ドット / ハイスループット / スクリーニング / Aβ / タウ / オリゴマー / アルツハイマー / シヌクレイン / 医薬品探索 / 認知症 / アルツハイマー病 / アミロイドβ / αシヌクレイン |
Outline of Final Research Achievements |
Amyloid disease such as Alzheimer's disease is triggered by aggregation of amyloid protein to develop it, and therefore the aggregation inhibitor is useful for prevention and treatment of disease. In this study, we developed an automated microliter-scale high-throughput screening system (MSHTS system) for amyloid β (Aβ) aggregation inhibitors applying real-time imaging method of Aβ aggregation using quantum dots. Furthermore, we screened for inhibitory substances using this automated system and analyzed the structure-activity relationship of active substances. In addition to expanding the MSHTS method to other amyloids (tau, α-synuclein, and amyloid A), we developed a new screening method for inhibitors of amyloid oligomer formation with high neurotoxicity.
|
Academic Significance and Societal Importance of the Research Achievements |
認知症の過半数を占めるアルツハイマー病の発症には、アミロイドβやタウと呼ばれるタンパク質の脳内での凝集と蓄積が関与しているため、凝集を抑制する物質は病気の予防や治療に有用である。本研究では、不純物を含む天然物エキスのアミロイド凝集抑制活性であっても微量かつ効率的に評価できる自動分析システムの開発に成功し、本手法を用いて様々な凝集抑制物質を発見してきた。今後、本手法や新たに見つかった化合物を用いることで、認知症予防に関する研究が飛躍的に進展することが期待される。
|
Report
(4 results)
Research Products
(71 results)
-
-
-
-
-
-
-
-
-
-
-
[Journal Article] Structure-activity relations of rosmarinic acid derivatives for the amyloid beta aggregation inhibition and antioxidant properties2017
Author(s)
Taguchi Riho, Hatayama Koki, Takahashi Tomohito, Hayashi Takafumi, Sato Yuki, Sato Daisuke, Ohta Kiminori, Nakano Hiroto, Seki Chigusa, Endo Yasuyuki, Tokuraku Kiyotaka, Uwai Koji
-
Journal Title
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume: 138
Pages: 1066-1075
DOI
Related Report
Peer Reviewed
-
-
-
-
-
[Journal Article] Mutually exclusive cooperative binding of myosin and cofilin to actin filaments involves cooperative conformational changes of actin.2016
Author(s)
Ngo KX, Umeki N, Kijima ST, Kodera N, Ueno H, Furutani-Umezu N, Nakajima J, Noguchi TQP, Nagasaki A, Tokuraku K, Uyeda TQP
-
Journal Title
Scientific Reports
Volume: 6
Issue: 1
Pages: 35449-35449
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
-
-
[Journal Article] Simple primary β-amino alcohol catalyzed enantioselective Diels-Alder reaction of 3-hydroxy-2-pyridones2016
Author(s)
Takahashi, T., Reddy, U.V.S., Kohari, Y., Seki, C., Furuyama, T., Kobayashi, N., Okuyama, Y., Kwon, E., Uwai, U., Tokiwa, M., Takeshita, M., Nakano, H.
-
Journal Title
Tetrahedron Letters
Volume: 57
Issue: 51
Pages: 5771-5776
DOI
Related Report
Peer Reviewed
-
[Journal Article] 2-Azanorbornane-based amine organocatalyst for enantioselective aldol reaction of isatins with ketones2016
Author(s)
Ogasawara, A., Reddy, U.V.S., Seki, C., Okuyama, Y., Uwai, K., Tokiwa, M., Takeshita, M., Nakano, H.
-
Journal Title
Tetrahedron: Asymmetry
Volume: 27
Issue: 20-21
Pages: 1062-1068
DOI
Related Report
Peer Reviewed
-
[Journal Article] Simple Primary Amino Amide Organocatalyst for Enantioselective Aldol Reactions of Isatins with Ketones2016
Author(s)
Kimura, J., Reddy, V.S., Kohari, Y., Seki, C., Mawatari, Y., Uwai, K., Okuyama, Y., Kwon, E., Tokiwa, M., Takeshita, M., Iwasa, T., Nakano, H.
-
Journal Title
European Journal of Organic Chemistry
Volume: 2016
Pages: 3748-3756
Related Report
Peer Reviewed
-
[Journal Article] Effects of Sesaminol Feeding on Brain Aβ Accumulation in a Senescence-Accelerated Mouse-Prone 82016
Author(s)
Katayama, S., Sugiyama, H., Kushimoto, S., Uchiyama, Y., Hirano, M., Nakamura, S
-
Journal Title
J. Agric. Food Chem.
Volume: 64
Issue: 24
Pages: 4008-4013
DOI
Related Report
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
[Presentation] Discovery of lead compounds targeting Amyloid-β aggregation from aromatic low-molecular compounds2017
Author(s)
Ando, Y., Ota, K., Ito, I., Kikuchi, H., Oshima, Y., Endo, Y., Uwai, K., Tokuraku, K.
Organizer
Joint Seminar on Environmental Science and Disaster Mitigation Research 2017
Place of Presentation
北海道、室蘭工業大学
Related Report
Int'l Joint Research
-
-
[Presentation] Function of Gloiopeltis furcata as Aggregation Inhibitor for Aβ, evaluated by a microliter-scale high-throughput screening system2017
Author(s)
Yo, T., Itada, T., Takahashi, T., Ogara, T., Uwai, K., Tokuraku, K.
Organizer
Joint Seminar on Environmental Science and Disaster Mitigation Research 2017
Place of Presentation
北海道、室蘭工業大学
Related Report
Int'l Joint Research
-
[Presentation] Structure-activity Relationship of Amyloid β Aggregation Inhibitors: Dibenzylideneacetone Derivatives2017
Author(s)
Hatayama, K., Taguchi, R., Ando, Y., Seki, C., Nakano, H., Tokuraku, K., Uwai, K.
Organizer
Joint Seminar on Environmental Science and Disaster Mitigation Research 2017
Place of Presentation
北海道、室蘭工業大学
Related Report
Int'l Joint Research
-
-
-
-
-
-
[Presentation] Effects of seaweeds extracts for amyloid β aggregation2016
Author(s)
Takahashi, T., Yo, T., Ogara, T., Yasui, H., Uwai, K., Tokuraku, K.
Organizer
The 7th Forum on Studies of Environmental and Public Health Issues in the Asian mega-Cities
Place of Presentation
北海道、室蘭工業大学
Year and Date
2016-09-01
Related Report
Int'l Joint Research
-
[Presentation] Effect of the number and position of phenolic hydroxyl groups on the Aβ aggregation inhibition of polyphenols2016
Author(s)
Hatayama, K., Taguchi, R., Takahashi, T., Seki, C., Nakano, H., Tokuraku, K., Uwai, K.
Organizer
The 7th Forum on Studies of Environmental and Public Health Issues in the Asian mega-Cities
Place of Presentation
北海道、室蘭工業大学
Year and Date
2016-09-01
Related Report
Int'l Joint Research
-
[Presentation] Inhibitory mode of rosmarinic acid derivatives against amyloid - beta aggregation: their ThT and MSHTS analyses2016
Author(s)
Taguchi, R., Takahashi, T., Hatayama, K., Hashi, Y., Seki, C., Nakano, H., Tokuraku, K., Uwai, K.
Organizer
The 7th Forum on Studies of Environmental and Public Health Issues in the Asian mega-Cities
Place of Presentation
北海道、室蘭工業大学
Year and Date
2016-09-01
Related Report
Int'l Joint Research
-
-
-
-