2021 Fiscal Year Final Research Report
A strategy for Alzheimer's disease therapy by targeting neurodegenerative disease-associated one subtype of microglia
Project/Area Number |
19K07004
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 47010:Pharmaceutical chemistry and drug development sciences-related
|
Research Institution | Nigata University of Phermacy and Applied Life Sciences |
Principal Investigator |
|
Project Period (FY) |
2019-04-01 – 2022-03-31
|
Keywords | アルツハイマー病 / アルツハイマー病モデルマウス / 1型ミクログリア / オリゴマー状Aβ / 9F5抗体 / スカベンジャー受容体 / Gpnmb欠損マウス / Truncated GPNMB |
Outline of Final Research Achievements |
In this study, we conducted a study on the development of a treatment for Alzheimer's disease targeting neurodegenerative disease-associated type 1 microglia (Gpnmb-positive type 1 MG). Memory impairment in 9-month-old Alzheimer's disease model mice improved when the Gpnmb gene was halved, but worsened when the Gpnmb gene was completely deficient. In an in vitro experimental system, the clearance activity of oligomeric amyloid β (o-Aβ) by type 1 MG was competitively suppressed by the 9F5 antibody. This result suggests that the 9F5 antigen (truncated GPNMB) functions as a novel scavenger receptor for o-Aβ.
|
Free Research Field |
神経化学
|
Academic Significance and Societal Importance of the Research Achievements |
本研究における重要な成果として、1型ミクログリアに発現する9F5抗原(truncated GPNMB)は、オリゴマー状アミロイドβのスカベンジャー受容体であるという新規仮説を提示することができた。この成果は、オリゴマー状アミロイドβやGPNMBが関わる難治性疾患の病態の解明、並びに治療薬の開発など、今後の応用研究につながりうる重要な知見であると考えられる。
|