2014 Fiscal Year Final Research Report
Astrocyte protection by targeting lipid rafts
Project/Area Number |
24591279
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Neurology
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Research Institution | Fujita Health University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
MUTOH Tatsuro 藤田保健衛生大学医学部, 脳神経内科学, 教授 (60190857)
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Project Period (FY) |
2012-04-01 – 2015-03-31
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Keywords | アクアポリン4 / 視神経脊髄炎 / 脂質ラフト |
Outline of Final Research Achievements |
Neuromyelitis optica (NMO)-IgG is highly specific diagnostic marker for NMO and contributes directly to disease pathogenesis. The target antigen of NMO-IgG was identified as aquaporin-4 (AQP4). There ae two major AQP4 isoforms, M1 and M23. We generated M1, M23, and M1/M23 co-expressing astrocyte cell lines. Most of M1 is localized in lipid raft on the membrane; in contrast, M23 is localized in both lipid raft and non-raft fractions when expressed independently. When both M1 and M23 are expressed, the majority of AQP4 is localized in lipid rafts. Cholesterol depletion with methyl-b-cyclodextrin or simvastatin resulted in the relocation of AQP4 from lipid rafts to non-rafts fraction. This change in the localization of AQP4 on membrane significantly reduced complement-dependent cytotoxic effects of NMO-IgG without affecting AQP4 orthogonal arrays. Thus, these data strongly suggest that the targeting of AQP4 in the lipid rafts is closely related to the pathogenic effects of NMO-IgG.
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Free Research Field |
神経内科
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