| Project/Area Number |
10307015
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Niigata University |
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Principal Investigator |
TSUJI Shoji Niigata University, Brain Research Institute, Professor, 脳研究所, 教授 (70150612)
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| Co-Investigator(Kenkyū-buntansha) |
NAKANO Ryoichi Niigata University, Medical Hospital, Assistant, 医学部・附属病院, 助手 (00262444)
INUZUKA Takashi Gifu University, School of Medical, Professor, 医学部, 教授 (50184734)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥29,000,000 (Direct Cost: ¥29,000,000)
Fiscal Year 1999: ¥8,600,000 (Direct Cost: ¥8,600,000)
Fiscal Year 1998: ¥20,400,000 (Direct Cost: ¥20,400,000)
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| Keywords | amyotrophic lateral sclerosis / motor neuron diseases / conformational disease / Cu / Zn superoxide dismutase / SOD1 / aggregate bodies / transgenic mouse / neurodegeneration / ALS(amyotrophic lateral sclerosis) / Lewy body / inclusion body / neurodegeneration / conformation / apoptosis / familial ALS |
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| Research Abstract |
This research was aimed to elucidate molecular mechanisms of neurodegeneration in amyotrophic lateral sclerosis (ALS), and, furthermore, to develop therapeutic strategies for ALS. The project focused on 1. detailed mutational analysis of Cu/Zn SOD gene in familial ALS, 2. analysis of conformational changes of mutant Cu/Zn SOD proteins, and 3. creation of transgenic mice for familial ALS. Among 33 families with familial ALS, we have identified 7 mutations in the SOD1 gene including 3 novel ones (Ala4Thr, Cys111Tyr and Glu133Stop). By transient expression of mutant Cu/Zn SOD proteins in COS cells, we have found that the mutant Cu/Zn SOD proteins possesses properties for aggregate formation and altered mobility on SDS-PAGE analysis, supporting that the mutant proteins have conformations changes. We have established transgenic mouse lines carrying Ala4Thr and Ile113Thr, of which Ile113Thr mice have developed muscular weakness in the hindlegs. Based on the accomplishments obtained through this project, molecular mechanisms of neurodegeneration caused by mutant Cu/Zn SOD proteins will further be investigated.
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