The analysis of neurodegenerative processes and changes of protein interaction of tau by mutation.
| Project/Area Number |
24591711
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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 |
Psychiatric science
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| Research Institution | Osaka University |
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Principal Investigator |
TANAKA Toshihisa 大阪大学, 医学(系)研究科(研究院), 准教授 (10294068)
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| Co-Investigator(Kenkyū-buntansha) |
KUDO Takashi 大阪大学, 保健センター, 教授 (10273632)
MORIHARA Takashi 大阪大学, 医学(系)・研究科(研究院), 助教 (90403196)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | タウ蛋白 / リン酸化 / 認知症 |
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| Outline of Final Research Achievements |
To elucidate the neurodegenerative mechanisms in FTDP-17, interaction between tau and 14-3-3 protein was investigated. Affinity between two proteins was increased in mutated tau protein than in wiled typed tau protein, however the affinity increased at the same extent in both wild typed tau and mutated tau. Then aggregation was monitored and aggregation processes were more facilitated in mutated tau than in wild typed tau, however the aggregation was completely attenuated when tau was phosphorylated. Next effects of phosphorylation of tau at Ser214 were investigated, and intracellular degradation of tau is more facilitated in S214A mutated tau-transfected cells than in wiled typed tau –transfected cells. And involvement of PSA (Puromycin sensitive aminopeptidase) was also investigated. PSA can degrade tau in vitro at only at the N-terminal site, but cannot lead to complete digestion. However attenuation of PSA activity in cultured cells, induced accumulation of tau protein.
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Report
(4 results)
Research Products
(9 results)
