Development of a strategy for Alzheimer's disease therapy by agent to control function and differentiation of microglial subtypes
| Project/Area Number |
16K08328
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Drug development chemistry
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| Research Institution | Nigata University of Phermacy and Applied Life Sciences |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | アルツハイマー病 / 記憶障害 / レチノイド / レチノイン酸受容体 / レチノイドX受容体 / 肝臓X受容体 / ミクログリア亜種 / 9F5抗原 / １型ミクログリア / GPNMB / 視覚障害 / 脳白質障害 / 精神疾患 / 強迫性障害 / 毛繕い / Am80 / Bexarotene / truncated GPNMB / ２型ミクログリア / モノクローナル抗体 / GFPノックインマウス / ミクログリアサブタイプ / メラノコルチン関連ペプチド |
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| Outline of Final Research Achievements |
In this study, we focused on Bexarotene, which is the only clinically introduced RXR agonist, instead of the RXR agonist (HX630) we used so far, for the early realization of “AD therapy by RAR:RXR dual agonists". Then, it was investigated whether combined treatment with RAR agonist Tamibarotene (Am80) could significantly improve AD pathology. In addition, we advanced the analysis of a marker molecule of type 1 MG (9F5 antigen, Gpnmb) that is functionally different from type 2 MG. Moreover, we aimed at the development of AD treatment by controlling the function and differentiation of MG subtypes by investigating whether the molecule becomes a novel therapeutic target molecule for AD.
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| Academic Significance and Societal Importance of the Research Achievements |
１型ミクログリアに発現するGPNMBは、AD病態の悪化に関与する可能性が初めて明らかとなった。本研究はGPNMBがアルツハイマー病の記憶障害に寄与する分子であることを初めて示唆するもので、今後より詳細な分子機序の解明や適切な治療薬の開発を検討するための第一歩である。
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Report
(4 results)
Research Products
(20 results)
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[Journal Article] The novel monoclonal antibody 9F5 reveals expression of a fragment of GPNMB/osteoactivin processed by furin-like protease(s) in a subpopulation of microglia in neonatal rat brain.2016
Author(s)
Kawahara K, Hirata H, Ohbuchi K, Nishi K, Maeda A, Kuniyasu A, Yamada D, Maeda T, Tsuji A, Sawada M, Nakayama H.
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Journal Title
Glia
Volume: 64
Issue: 11
Pages: 1938-1961
DOI
NAID
Related Report
Peer Reviewed / Open Access
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