Astrocyte protection by targeting lipid rafts

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591279
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Fujita Health University
• Principal Investigator: ASAKURA Kunihiko 藤田保健衛生大学, 医学部, 教授 (50333159)
• 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)
• Project Period (FY): 2012-04-01 – 2015-03-31
• 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.

Free Research Field

神経内科