Clarification of the role of brain-reparative lipids for the novel concept of dyslipidemia

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02820
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: Tokyo Medical and Dental University (2023); Tokyo Metropolitan Institute of Medical Science (2021-2022)
• Principal Investigator: Takashi Shichita 東京医科歯科大学, 難治疾患研究所, 教授 (00598443)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 脳梗塞 / 神経修復 / 脳修復的脂質

Outline of Final Research Achievements

While the brain generally struggles to regenerate after injury, our study reveals a previously unknown self-repair mechanism. We found that damaged neurons release an enzyme called PLA2G2E, which produces DGLA which is essential for activating functional recovery mechanisms after ischemic stroke. When PLA2G2E is lacking, PADI4 is also reduced, which controls the activity of genes involved in recovery after stroke. Our analysis shows that PADI4 activates these recovery genes through a process called histone citrullination. Among the various substances derived from DGLA, we identified 15-HETrE as the one responsible for stimulating PADI4 production in surviving neurons. Giving 15-HETrE to stroke-affected individuals improved their recovery. These findings highlight the brain's remarkable capacity for self-repair, triggered by specific lipids produced in response to injury. This discovery opens new avenues for developing therapies to enhance recovery after stroke and other brain injuries.

Free Research Field

脳卒中学

Academic Significance and Societal Importance of the Research Achievements

本研究課題によって発見できた脳修復的脂質は食事で摂取することにより脳に蓄積させることが可能である。脳機能回復を促進させる食事療法の開発のほか、実際に脳修復的脂質が不足している患者（脳梗塞、軽度認知障害、心筋梗塞、糖尿病、加齢など）が存在することが既に知られているため、脳修復作用が低下している患者をスクリーニングする診断技術、検査薬の開発が期待できる。既にPCT出願済みであり、新たな脂質異常症の概念の確立に向けた構想を練っている。