| Project/Area Number |
16K09697
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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, 医歯学総合研究科, 客員研究員 (30511802)
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| Co-Investigator(Kenkyū-buntansha) |
高嶋 博 鹿児島大学, 医歯学域医学系, 教授 (80372803)
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| Research Collaborator |
Fukata Masaki
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 筋けいれん / ニューロミオトニア / アイザックス症候群 / 抗VGKC複合体抗体 / 病態マーカー / イオンチャネル / 自己抗体 / 不眠症 / 質量分析 / 後根神経節細胞 / 神経科学 / 神経内科学 / 神経病態免疫学 / 標的抗原解析 |
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| Outline of Final Research Achievements |
Voltage-gated potassium channel (VGKC) complex auto-antibodies were initially identified in Isaacs’ syndrome (IS), which is characterized by muscle cramps and neuromyotonia. These antibodies were subsequently identified in patients with Morvan’s syndrome (MoS). The antibodies have also been detected in a patient with limbic encephalopathy (LE) presenting with prominent amnesia and frequent seizures. Autoantibodies against the extracellular domains of VGKC complex proteins, leucine-rich glioma-inactivated 1 (LGI1), and contactin-associated protein-2 (Caspr2), occur in patients with IS, MoS, and LE. Novel information has been generated regarding autoantibody disruption of the physiological functions of target proteins. LGI1 antibodies neutralize the interaction between LGI1 and ADAM22, thereby reducing the synaptic AMPA receptors. It may be that the main action is on inhibitory neurons, explaining why the loss of AMPA receptors causes amnesia, neuronal excitability and seizures.
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| Academic Significance and Societal Importance of the Research Achievements |
チャネル蛋白に加え、チャネルと複合体を形成する蛋白抗原に着目した。候補遺伝子を一つずつCBAで検討するのだけではなく、一例ずつことなる複数の抗原について網羅的に解析する。この方法は効率が良いだけではなく、未知の新規抗原を同定することが出来る。一自己抗体→一疾患という今までの単純なパラダイムではなく、症例毎に、自己抗体の組み合わせやその量比による症状に差異を解析することが出来る。
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