| Project/Area Number |
25461286
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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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| Research Field |
Neurology
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| Research Institution | Kagoshima University |
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Principal Investigator |
Watanabe Osamu 鹿児島大学, 医歯学域 医学部・歯学部附属病院, 講師 (30511802)
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| Co-Investigator(Kenkyū-buntansha) |
KISHIDA Shosei 鹿児島大学, 学術研究院 医歯学域医学系, 教授 (50274064)
Takashima Hiroshi 鹿児島大学, 学術研究院 医歯学域医学系, 教授 (80372803)
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| Co-Investigator(Renkei-kenkyūsha) |
Fukata Masaki 大学共同利用機関法人 自然科学研究機構, 生理学研究所, 教授 (00335027)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 標的抗原解析 / イオンチャネル / 自己抗体 / LGI1 / AMPA受容体 / VGKC / 自己免疫性脳炎 / 新規標的抗原 |
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| Outline of Final Research Achievements |
We established a potential molecular mechanism for the pathogenic role of antibodies to leucine-rich, glioma inactivated 1 (LGI1), which are found in patients with limbic encephalitis (an acquired autoimmune condition presenting with memory loss, temporal lobe seizures and personality change, associated with swelling and inflammation of the medial temporal lobe, with a good response to immunotherapies). LGI1 is a secreted protein that binds to both a disintegrin and metalloproteinase domain 23 (ADAM23) presynaptically, where it is a component of a ‘voltage-gated potassium channel (VGKC) complex’, and ADAM22 postsynaptically, where it interacts with AMPA receptors.
We show that the LGI1 antibodies from patients with limbic encephalitis interfere with the LGI1/ADAM22 interaction, leading to a loss of postsynaptic AMPA receptors. This is a novel finding, which begins to establish a mechanism of action for the LGI1 antibodies.
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