Research Project
Grant-in-Aid for Early-Career Scientists
アルツハイマー病の発症にはアミロイドβの凝集体の一種・アミロイドβオリゴマーが関与するとされている。アミロイドβオリゴマーは神経細胞内外の様々な部位に局在すると報告されているが、どの部位のアミロイドβオリゴマーが神経変性の原因であるかは不明である。そこで本研究ではアミロイドβオリゴマーを選択的に分解するプロテアーゼを開発し、これを用いて部位ごとにアミロイドβオリゴマーが与える神経変性機構を解析する。
In this research project, a protease with amyloid-β (Aβ) oligomer selectivity, a drug target for Alzheimer's disease, was developed. Neprilysin was selected as the protease to degrade Aβ oligomer. As a result, recombinant production of Aβ oligomer-binding peptide-fused neprilysin with retained enzyme activity was successfully achieved. It was also found that the multivalency effect is important for the binding of peptides to Aβ oligomers. Future analysis of cells and tissues in which local Aβ oligomers are lowered by proteolysis is expected to reveal the action that triggers cell death.
Aβオリゴマーを標的とした二つの抗体医薬が上市され、認知機能低下を抑制する薬効が報告されている。しかし、今なおAβオリゴマーがどのように神経細胞を障害するのか、そのメカニズムは明らかでない。本研究課題の成果を基盤としそのメカニズムを解明することができれば、新しい創薬ターゲットの発見や高価な抗体医薬に変わる新薬の開発につながると期待できるため、その学術的・社会的意義は大きい。
All 2023 2022 2021 2020 2019
All Journal Article (19 results) (of which Int'l Joint Research: 6 results, Peer Reviewed: 19 results, Open Access: 19 results) Presentation (36 results) (of which Int'l Joint Research: 15 results) Patent(Industrial Property Rights) (1 results)
Veterinary Pathology
Volume: 60 Issue: 2 Pages: 203-213
10.1177/03009858221148511
CHROMATOGRAPHY
Volume: 43 Issue: 2 Pages: 73-77
10.15583/jpchrom.2022.008
ACS Chem Biol
Volume: 17 (7) Issue: 7 Pages: 1703-1713
10.1021/acschembio.1c00904
Int J Mol Sci
Volume: 23 (23) Issue: 23 Pages: 14588-14588
10.3390/ijms232314588
Journal of Molecular Liquids
Volume: 366 Pages: 120175-120175
10.1016/j.molliq.2022.120175
Volume: 23 (12) Issue: 12 Pages: 6467-6467
10.3390/ijms23126467
J Mater Chem B
Volume: 10 (43) Issue: 43 Pages: 8960-8969
10.1039/d2tb01638a
Biosensors and Bioelectronics
Volume: 203 Pages: 114027-114027
10.1016/j.bios.2022.114027
Volume: 22(23) Issue: 23 Pages: 12780-12780
10.3390/ijms222312780
International Journal of Molecular Sciences
Volume: 22 Issue: 23 Pages: 13159-13159
10.3390/ijms222313159
Sensors (Basel)
Volume: 11(11) Issue: 11 Pages: 1617-1617
10.3390/biom11111617
Nucleic Acids Res
Volume: 49 Issue: 11 Pages: 6069-6081
10.1093/nar/gkab388
Data Brief
Volume: 36 Pages: 107028-107028
10.1016/j.dib.2021.107028
Biosens Bioelectron
Volume: 178 Pages: 113030-113030
10.1016/j.bios.2021.113030
Mar Biotechnol (NY)
Volume: 23(1) Issue: 1 Pages: 31-38
10.1007/s10126-020-09997-w
Volume: 20(14) Issue: 14 Pages: 3878-3878
10.3390/s20143878
Bioorganic & medicinal chemistry letters
Volume: 29 (14) Issue: 14 Pages: 1807-1811
10.1016/j.bmcl.2019.05.009
physica status solidi (b)
Volume: 257 Issue: 2 Pages: 1900376-1900376
10.1002/pssb.201900376
Nucleic acid therapeutics
Volume: 29 (4) Issue: 4 Pages: 224-229
10.1089/nat.2018.0761