| Project/Area Number |
26461294
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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 | The University of Tokushima |
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Principal Investigator |
KAWARAI Toshitaka 徳島大学, 大学院医歯薬学研究部(医学系), 講師 (50614137)
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| Co-Investigator(Kenkyū-buntansha) |
梶 龍兒 徳島大学, 大学院医歯薬学研究部(医学系), 教授 (00214304)
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| Co-Investigator(Renkei-kenkyūsha) |
IMOTOI Issei 徳島大学, 大学院医歯薬学研究部, 教授 (30258610)
TAJIMA Atsushi 金沢大学, 医学系, 教授 (10396864)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
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| Keywords | 運動ニューロン病 / TFG / 運動ニューロン死 / 細胞内輸送 / 凝集体形成 / 小胞体 / ゴルジ体 / 筋萎縮性側索硬化症 / 痙性対麻痺 / 末梢神経障害 |
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| Outline of Final Research Achievements |
We performed biological characterization of neural cells derived from hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) patient induced pluripotent stem cells (iPSCs), and revealed proteasome dysfunction when the iPSCs carrying the clinical mutation, Pro285Leu, in tropomyosin-receptor kinase fused gene (TFG). We also analyzed the animal model for HMSN-P, transgenic mice over expressing human mutant TFG, and demonstrated replication of intraneuronal aggregations, including TFG, optineurin, and TAR DNA binding protein 43 (TDP-43). The model mice are undergoing therapeutic trial using phenylbutyrate, which has been demonstrated to be clinically and pathologically effective to decrease Tau aggregation in transgenic mice via activation of autophagy.
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