| Project/Area Number |
16K09685
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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 | Fujita Health University |
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Principal Investigator |
Mutoh Tatsuro 藤田医科大学, 医学部, 教授 (60190857)
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| Co-Investigator(Kenkyū-buntansha) |
朝倉 邦彦 藤田医科大学, 医学部, 教授 (50333159)
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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 |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | AD / PD / α-synuclein / Tau蛋白 / アミロイドβ / 糖脂質 / 脂質ラフト / 神経栄養因子受容体 / ラフト / αーシヌクレイン / タウ蛋白 / 脂質－蛋白相互作用 / パーキンソン病 / アルツハイマー病 / 神経細胞死 / 蛋白修飾の異常 |
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| Outline of Final Research Achievements |
In this study,we identified GM1 biding site in Trk neurotrophin receptor by using deletion mutant analyses.The proposed binding site of GM1 ganglioside within Trk protein was probed to be in the juxtamembrane region of the Trk protein. Stable transfectant of these muant trk gene did not show any responses to its cognate ligand, NGF biochemically and morphologically (paper in preparation).
Another achievement of the persent study is the discovery of disease specific lipidomic profiles. We performed lipidomic analyses of cerebrospinal fluid from neurologically normal controls (NNC) and patients with various neurodegenerative disorders such as Parkinon's and Alzheimer's dieseases and motor neuron disease as well.LC-Ms/Ms analyses disclosed that in NNC, there are significant differences in lipids profiles with age and gender, which be very important for future evaluation of their comparison with disease patients. Morevoer, we identified disease specific lipidmic profiles for each diseases.
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| Academic Significance and Societal Importance of the Research Achievements |
これまで知られて来なかった脂質類による細胞膜蛋白の翻訳後修飾の実態を神経栄養因子受容体を例にとり、その詳細な実態を解明出来た．さらに、ADやPD等の神経難病疾患での髄液中糖脂質プロファイル化を初めて明らかにすることが出来た．この詳細にプロファイルは今後各神経難病の成因解明に取り組む研究に革新的な情報提供をする事が出来た事を意味し、全く新たな治療法開発の可能性を示唆する重要な研究と成った．
さらに、こうした糖脂質は食物にも大量に含まれており、上記プロファイルパターンから神経障害を発生させないような食事療法の可能性を切り開くものである．
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