Search for compounds that control metabolic regulators in the brain

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K19951
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Health science and related fields
• Research Institution: National Center for Geriatrics and Gerontology
• Principal Investigator: Taguchi Akiko 国立研究開発法人国立長寿医療研究センター, 統合加齢神経科学研究部, 部長 (80517186)
• Co-Investigator(Kenkyū-buntansha): 田之頭 大輔 国立研究開発法人国立長寿医療研究センター, 統合加齢神経科学研究部, 研究員 (80724575)
• Project Period (FY): 2017-06-30 – 2020-03-31
• Keywords: ドラッグリポジショニング / 化合物 / 糖尿病治療薬 / 糖代謝調節経路 / 脳 / 認知症 / 糖尿病

Outline of Final Research Achievements

We found that 1) prolonged treatment with metformin, a biguanide antidiabetic medication, improves hippocampal dysfunctions including cognitive decline in middle-aged type2 diabetes (T2DM) model mice, 2) chronic treatment with metformin modulates glucose metabolism-related signaling factors1 together with activation of targets of metformin in the hippocampus when it improves hippocampal dysfunctions in T2DM model mice, 3) chronic therapy with metformin restores hippocampal functions in middle-aged DIO mice, independently of the hypoglycemic effect, 4) novel modification of hippocampal glucose metabolism-related signaling factor2 is associated with metformin treatment-induced improvements in hippocampal function in T2DM model mice, and 5) existing compounds may induce alterations in glucose metabolism-related signaling factors in the hippocampus.

Free Research Field

神経内分泌代謝学

Academic Significance and Societal Importance of the Research Achievements

本研究は、ドラッグリポジショニング作用として既存糖尿病治療薬が認知機能に有益な作用を与えること、その際、脳の糖代謝調節経路が関与することを明らかにした点で学術的意義が深い。今回の結果と解析系を基盤に、他の糖尿病治療薬を含む既存薬のリポジショニング効果について今後更に精査することで、脳の糖代謝調節経路を介した既存薬の新たな効果の発見に繋がる可能性が考えられる。