2022 Fiscal Year Final Research Report
Study of drug discovery and biomarker for depression based on glial antidepressant receptor (LPA1)
| Project/Area Number |
18H02756
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 52030:Psychiatry-related
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| Research Institution | Kumamoto University (2020-2022)
Department of Clinical Research, National Hospital Organization Kure Medical Center (2018-2019) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
功刀 浩 帝京大学, 医学部, 教授 (40234471)
井上 飛鳥 東北大学, 薬学研究科, 教授 (50525813)
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| Project Period (FY) |
2018-04-01 – 2023-03-31
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| Keywords | うつ病 / リゾリン脂質代謝 / リゾフォスファチジン酸 / リゾフォスファチジン酸受容体１ / 抗うつ薬 / 創薬 / 栄養療法 |
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| Outline of Final Research Achievements |
In patients with depression,docosahexaenoic acid-lysophosphatidic acid (DHA-LPA), a lysophospholipid, and autotaxin, an LPA synthase, were decreased and correlated with depressive symptoms. On the other hand, preclinical studies revealed that LPA receptor 1 (LPA1) agonists have antidepressant effects, and a library of existing therapeutic agents was used for primary screening with the LPA1 assay. In summary, we discovered the possibility of abnormal lysophospholipid metabolism in the pathogenesis of depression, and furthermore, identified LPA1 agonists as new drug target molecules, creating the basis for drug repositioning.
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| Free Research Field |
精神医学
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| Academic Significance and Societal Importance of the Research Achievements |
うつ病は近年増加が著しく2020年の障害調整生存年（DALY）で虚血性心疾患に次ぐ2位で、社会経済的な影響が大きい疾患である。特に難治化が問題となっているうつ病において、今までの病態理解・創薬の視点と大きく異なった、脂質メディエーターという新しい視点の生物学的病態を明らかにして、その病態に基づいた治療標的を明らかにした。従って、今回の発見は新しいうつ病治療薬や栄養療法の開発につながる可能性があり、学術的意義や社会的意義は高いと考えられる。
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