Development of a strategy for Alzheimer's disease therapy by agent to control function and differentiation of microglial subtypes

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08328
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Drug development chemistry
• Research Institution: Nigata University of Phermacy and Applied Life Sciences
• Principal Investigator: KAWAHARA Kohichi 新潟薬科大学, 薬学部, 准教授 (10347015)
• Project Period (FY): 2016-04-01 – 2019-03-31
• 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

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.

Free Research Field

神経化学

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。