Prevention and Treatment of Alzheimer's Disease by Activation of Retinoid X Receptor Heterodimers.
Project/Area Number |
17K08352
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Natural medicines
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Research Institution | Aichi Gakuin University |
Principal Investigator |
INOUE MAKOTO 愛知学院大学, 薬学部, 教授 (50191888)
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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Keywords | レチノイドX受容体 / 核内受容体 / アルツハイマー病 / 天然由来アゴニスト / 肝X受容体 / AD治療薬 / 脳内炎症 / 天然由来RXRアゴニスト / 抗炎症作用 / アルツハイマー病マウスモデル / ホオノキオール誘導体 / Liver X受容体 / ABCA1 / 薬学 / 天然活性物質 |
Outline of Final Research Achievements |
The mechanism underlying the development of Alzheimer's disease (AD) has not been fully elucidated, and there is currently no fundamental therapeutic drug for AD. In this study, we investigated the biological activity of a naturally-occurring agonist of the nuclear receptor retinoid X receptor (RXR) with the aim of developing a therapeutic drug for AD. As a result, the naturally-occurring RXR agonists and semi-synthetic RXR agonists found in our laboratory showed some biological activities such as neuronal protective and anti-inflammatory effects with a mechanism of action that has not been reported in existing synthetic RXR agonists, and further they showed interesting cooperative effects with liver X receptor agonists in cells and AD model animals. The results of this study show new possibilities for the development of preventive and therapeutic agents for AD.
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Academic Significance and Societal Importance of the Research Achievements |
AD型認知症患者は超高齢化社会の日本で急速に増加しており、有効な治療薬が存在しない現在においてADの予防法及び根本的な治療薬の開発は喫緊の課題である。本研究では合成RXRと異なる遺伝子発現プロファイルを持つ天然由来RXRアゴニストが新たな作用機序で効果を発現するとともに、パートナーNRアゴニストとの併用により、より効果的に脳機能を多面的に調節できる可能性を示し、天然由来RXRアゴニストは新たなAD治療薬の開発において有用な候補化合物あるいはシード化合物になると考えられた。
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Report
(4 results)
Research Products
(6 results)
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[Journal Article] Discovery and SAR of Natural-Product-Inspired RXR Agonists with Heterodimer Selectivity to PPARδ‐RXR2020
Author(s)
Ken-ichi Nakashima, Eiji Yamaguchi, Chihaya Noritake, Yukari Mitsugi, Mayuki Goto, Takao Hirai, Naohito Abe, Eiji Sakai, Masayoshi Oyama, Akichika Itoh, and Makoto Inoue
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Journal Title
ACS Chemical Biology
Volume: -
Issue: 6
Pages: 1526-1534
DOI
Related Report
Peer Reviewed
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