| Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| 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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