2016 Fiscal Year Final Research Report
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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| 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 |
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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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| Free Research Field |
プリオン学
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