2023 Fiscal Year Final Research Report
elucidation of mechanism of exacerbation in neuromyelitis optica and development of biomarkers that predict relapse severity
| Project/Area Number |
22K15717
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 52020:Neurology-related
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| Research Institution | International University of Health and Welfare |
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Principal Investigator |
Maimaitijiang Guzailiayi 国際医療福祉大学, トランスレーショナルニューロサイエンスリサーチセンター, 特任助教 (60887107)
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| Project Period (FY) |
2022-04-01 – 2024-03-31
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| Keywords | 視神経脊髄炎 / 脱髄疾患 / アストログリア / エキソソーム / バイオマーカー / コネキシン / 神経炎症 / 重症化 |
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| Outline of Final Research Achievements |
We discovered marked alterations of connexin 43 (Cx43)-truncated isoforms, which are produced upon stress, in serum exosomes from patients with neuromyelitis optica (NMO). At relapse, exosome GJA1-29 significantly elevated as compared with healthy controls (HCs) while exosome GJA1-11k significantly decreased at relapse and in remission compared with HCs. As a result, exosome 29k/11k ratio markedly increased at relapse compared with HCS and showed a positive correlation with disability in NMO. Serum exosome GJA1-29k markedly increased at acute phases in experimental autoimmune encephalomyelitis (EAE) in wild type mice. Such increase was completely abrogated in astroglia-specific Cx43-inducible conditional knockout mice with attenuated EAE at acute phase. These findings suggest that serum exosome GJA1-29k is derived from central nervous system astroglia and confers neuroinflammation. Therefore, serum GJA1-29k/11k ratio is suggested to be a novel biomarker for NMO exacerbation at relapse.
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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 |
NMOでは分子標的療法が臨床応用され、再発はよく抑えられるようになったが、急性期の重症化を軽減する有効な手段が乏しく、再発重症化の血液バイオマーカーは確立していない。本研究はNMO急性期の重症度に関係した全く新しい炎症性バイオマーカーを発見した価値あるものである。血清エキソソーム中のCx43-truncated isoformは、神経炎症の急性期には脳アストログリア由来で、GJA1-29kの増加は神経炎症の重症化に、GJA1-11kは神経炎症の軽減に寄与していると考えられ、病態に関与したバイオマーカーである点で意義が大きい。将来は、これらを標的とした急性期治療への道が開かれることが期待できる。
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