2023 Fiscal Year Final Research Report
Signal transduction to neuroinflammation and abnormal protein modification by neutral glycolipids
| Project/Area Number |
21K07446
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 52020:Neurology-related
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| Research Institution | Fujita Health University |
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Principal Investigator |
Mutoh Tatsuro 藤田医科大学, 大学病院, 特命教授 (60190857)
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| Co-Investigator(Kenkyū-buntansha) |
中嶋 和紀 岐阜大学, 糖鎖生命コア研究所, 准教授 (10442998)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | 神経炎症 / 蛋白異常凝集 / 情報伝達 / 神経細胞死 / 抗-中性糖脂質抗体 / 蛋白修飾 / セラミド合成酵素 / 脂肪酸鎖 |
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| Outline of Final Research Achievements |
In this study, we clarified a disease-specific glycolipids dysmetabolism and immune abnormalities in EMRN patients. Moreover, anti-NGL antibodies such as anti-lactosylceramide (LacCer) antibody inhibit nerve growth factor-induced Trk autophophorylation in neuronal cells. Moreover, increased intracellular LacCer contents can cause the neurotoxic change of astrocytes on neuronal cells.
Thus, these results strongly indicate EMRN can be caused by the abnormal glycolipid metabolism and abnormal activation of innate immune responses. The present studies might indicate new therapeutic approach using anti-innate immune therapy.
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| Free Research Field |
神経内科学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、これまで余り研究されて来なかった糖脂質特にラクトシルセラミドなどの中性糖脂質が脳脊髄根末梢神経炎などの神経炎症性疾患発生のシグナルトランジューサ―の機能を有する事、又全身でのinnate immunityの異常活性化が惹起される事を明確にした．こうした新知見は、抗innate immunity療法などの新規治療法がこれら神経炎症性疾患の試すべき治療法である事を明確にした点で、意義深い．又、抗中性糖脂質抗体の免疫的細胞生物学的役割の新たな側面を解明した点でブレークスルー的な成果を挙げた．
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