2022 Fiscal Year Final Research Report
Investigation on pathological implications of guidance molecules in neuro-immune-metabolism.
| Project/Area Number |
18H05282
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| Research Category |
Grant-in-Aid for Scientific Research (S)
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| Allocation Type | Single-year Grants |
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| Review Section |
Broad Section I
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| Research Institution | Osaka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
奥野 龍禎 大阪大学, 大学院医学系研究科, 准教授 (00464248)
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| Project Period (FY) |
2018-06-11 – 2023-03-31
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| Keywords | 神経免疫代謝連関 / 神経ガイダンス / セマフォリン |
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| Outline of Final Research Achievements |
To elucidate the regulatory mechanisms of immune and inflammatory cell activation and differentiation by regulatory molecules controlling neuroimmunometabolism, we found that LRRK2, the gene responsible for Parkinson's disease, a neurodegenerative disease, and its analog LRRK1 are responsible for the physiological activity of semaphorins through the regulation of activation of the small G protein Rab7. We found that LRRK2, a gene responsible for Parkinson's disease, and its analog LRRK1 are responsible for the physiological activity of semaphorins via regulating the activation of small G protein Rab7. Regarding the analysis of intracellular metabolic changes involved in immune and inflammatory cell differentiation, we found that activation of intracellular lipid metabolism via the mTOR-Sema6D-PPARγ pathway is essential during inhibitory macrophage differentiation and suppresses the development of enteritis.
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| Free Research Field |
内科学、免疫学
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| Academic Significance and Societal Importance of the Research Achievements |
免疫疾患の病態が単に免疫細胞の異常で生じるのでなく、神経系、代謝系、そして免疫系が相互に作用する中で、病態形成に関与していることが示された。従来、免疫疾患治療は生物学的製剤が標的とする免疫調節分子に向けられてきたが、今後包括的、俯瞰的な視点での薬剤開発に繋がる成果が期待される。また、慢性の疾患である自己免疫疾患治療の根本的な治癒に繋がる新しい視点を提供したことになる。
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