Prevention and Treatment of Alzheimer's Disease by Activation of Retinoid X Receptor Heterodimers.

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08352
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Natural medicines
• Research Institution: Aichi Gakuin University
• Principal Investigator: INOUE MAKOTO 愛知学院大学, 薬学部, 教授 (50191888)
• Project Period (FY): 2017-04-01 – 2020-03-31
• 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

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.

Free Research Field

天然薬物（天然物、生薬、漢方方剤）の生活習慣病や加齢性疾患に対する有効性を分子レベルで解析している。

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。