| Project/Area Number |
16K07071
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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 |
Neurochemistry/Neuropharmacology
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| Research Institution | Doshisha University |
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Principal Investigator |
WATANABE Shoji 同志社大学, 研究開発推進機構, 助教 (80462745)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | アルツハイマー病関連タンパク質 / タウ / 局在化機構 / 軸索 / 分子動態 / 軸索局在 / FRAP / リン酸化・脱リン酸化 / 蛋白質半減期 |
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| Outline of Final Research Achievements |
Tau is one of microtubule -associated proteins, and localizes to only the axon in healthy neuron. In contrast, Tau is mis-localized to the soma and dendrites in Alzheimer's disease and related disorders.Although the localization of Tau has been well known, the mechanisms for its localization have been poorly understood. The lack of an experimental system is taken as this reason.
Exogenously expressed Tau is readily mis-localized to the soma and dendrite in cultured rat hippocampal neurons. Then I constructed the original expression system. Using this system, I demonstrated that transient expression of Tau in immature neurons is important for the axonal localization. In addition, I found that the axonal localization of Tau did not require the interaction between Tau and microtubule by using this system and Tau deletion mutants. Moreover, I obtained results that proline-rich region 2 of Tau was extremely important for the molecular dynamics in neuron.
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| Academic Significance and Societal Importance of the Research Achievements |
高齢者人口の増加に伴い、アルツハイマー病を含む認知症の患者数も増加している。現在までに、アルツハイマー病関連タンパク質の一つであるタウに関して非常に多くの論文が報告されているが、局在化機構に着目した研究は未だ少ない。そこで、本研究ではタウの軸索局在に着目し、それを明らかにすることを目標に3年間の研究を進めた。
本研究で得られた結果は、学術的に新規な知見だけではなく、認知症の病態の一端を理解する新しい知見であると考えている。このことから、将来的に、病態の理解だけではなく創薬にも繋がる、学術的および社会的に意義のある研究であったといえる。
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