| Project/Area Number |
26461322
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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 | Hyogo Medical University |
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Principal Investigator |
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| Research Collaborator |
UKON Shinichirou 兵庫医科大学, 内科学(神経・脳卒中科), 大学院生
TATSUMI Yoshiki 兵庫医科大学, 内科学(神経・脳卒中科), 実験補助
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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 |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 軸索ジストロフィー / 質量顕微鏡 / 軸索輸送 / ユビキチン・プロテオソーム / オートファジー |
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| Outline of Final Research Achievements |
To elucidate an etiology of neuroaxonal dystrophy, dorsal ganglion neurons of the gracile axonal dystrophy (gad ) mice which are caused by an in-frame deletion including exons 7 and 8 of Uch-L1, encoding the ubiquitin carboxy-terminal hydrolase (UCH) isozyme (L1), were studied in vitro. Administration of antibodies against axonal flow motor molecules, or chemicals such as taxol or colchicine could not reproduce the similar pathology to axonal dystrophy. Lysosomal-associated membrane protein 1 (LAMP-1), microtubule-associated protein 1A/1B-light chain 3 (LC3), and the ubiquitin-binding protein p62 were, however, expressed intensively at the gracile nucleus on immunohistological study.
The present data suggest elevated function of autophagy in gad mice. Especially, p62 which is an autophagosome cargo protein may compensate for impaired proteolysis through the ubiquitin-proteasome pathway which causes accumulation of undigested organella.
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