Drug repositioning research targeting new pain control molecules, lysophospholipid acyltransferases

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K15309
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: National Center for Global Health and Medicine
• Principal Investigator: YAMAMOTO Shota 国立研究開発法人国立国際医療研究センター, その他部局等, 特任研究員 (50825693)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: ドラッグリポジショニング / 神経障害性疼痛 / リン脂質生合成酵素

Outline of Final Research Achievements

Neuropathic pain is a pathological chronic pain disorder in which even tactile stimuli are felt as pain. We have recently discovered that LPCAT2 and LPCAT3, the enzymes responsible for shaping the diversity of phospholipids, may be involved in the pathogenesis of neuropathic pain. In this study, we have identified which cell types in the nervous systems expresses LPCAT2 and LPCAT3, which are important in the development of neuropathic pain. Furthermore, we explored LPCAT2 and LPCAT3 inhibitors by screening using a library of approved drugs, and found several new inhibitor candidates. We hope that these findings will lead to the development of new analgesics in the future.

Free Research Field

神経薬理学

Academic Significance and Societal Importance of the Research Achievements

生体膜リン脂質の多様性の生理・病態学的な意義についてはブラックボックスである。本研究では，神経障害性疼痛病態に対して，リン脂質生合成酵素が重要な役割を果たすことを明らかにした。また，リン脂質生合成酵素を標的にしたドラッグリポジショニング研究を遂行し，阻害剤となりうる候補化合物を複数見出した。リン脂質生合成酵素が疼痛疾患に関わる詳細なメカニズムや阻害剤候補化合物の更なる検証が必要ではあるが，今後のリン脂質多様性の生物学，および，新規鎮痛薬開発の足がかりとなる成果であると考えられる。