Elucidation of the vesicular trafficking mechanism for prion propagation on the basis of our previous findings of the disturbed vesicular trafficking in prion disease
| Project/Area Number |
26293212
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial 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 |
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| Co-Investigator(Kenkyū-buntansha) |
矢野 雅司 徳島大学, 疾患酵素学研究センター, 技術員 (10531858)
千田 淳司 徳島大学, 疾患酵素学研究センター, 助教 (20437651)
原 英之 徳島大学, 疾患酵素学研究センター, 助教 (40469953)
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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 |
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2016: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2015: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2014: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
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| Keywords | プリオン / プリオン病 / ソーチリン / 蛋白質輸送 / 蛋白質分解 / ノックアウトマウス / 神経変性疾患 / プリオン蛋白質 / トランスジェニックマウス / アトラクチン / インスリン受容体 / ポストゴルジ小胞輸送 / 神経変性 / 小胞輸送 / 細胞膜蛋白質 / Tgマウス / ポストゴルジ輸送 |
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| Outline of Final Research Achievements |
We identified that sortilin promotes degradation of prions. Sortilin interacted with the normal and abnormal prion proteins and transported them to lysosomes for degradation. Downregulation of sortilin increased the abnormal prion protein in prion-infected cells. The normal prion protein was also increased by downregulation of sortilin in prion-uninfected cells. Interestingly, prion infection reduced sortilin by promoting lysosomal degradation of sortilin. Finally, we intracerebrally inoculated prions into sortilin-knockout (KO) and control wild-type (WT) mice. Sortilin-KO mice developed prion disease and died significantly earlier than WT mice. Sortilin-KO mice also accumulated the abnormal prion protein from the earlier stages of infection, compared to control WT mice. These results suggest that prions could propagate themselves through reducing sortilin.
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Report
(4 results)
Research Products
(12 results)
