| Project/Area Number |
20K16142
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 48040:Medical biochemistry-related
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| Research Institution | Niigata University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | USP10 / Nrf2 / p62 / Parkinsons disease / Neurodegeneration / Synuclein / Tau / G3BP1 / α-synuclein |
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| Outline of Research at the Start |
Accumulation of Tau or α-synuclein (αS) protein oligomers is toxic to neurons and cause neurodegeneration. The aim of study is to elucidate how G3BP1, USP10, p62 proteins control toxicity of Tau and αS oligomers by using cultured cells, mouse models and patient brains samples.
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| Outline of Final Research Achievements |
Parkinson's disease is characterized by cell death of dopaminergic neurons in the substantia nigra of the brain. We found that in a cell line derived from dopaminergic neurons, USP10 protein activates Nrf2, a transcriptional activator of the antioxidant genes, to suppress dopamine-induced reactive oxygen species production and cell death. USP10 increased the amount of phosphorylated p62 (p62/Ser-349), which induces the degradation of Keap1, a repressor of Nrf2, and activates Nrf2.
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| Academic Significance and Societal Importance of the Research Achievements |
酸化ストレスは、パーキンソン病を始めとする、多くの神経変性疾患の病因や病態に関与している。今回の成果は、USP10が神経細胞の抗酸化活性を活性化する重要な因子であることを明らかにした。また、USP10が酸化ストレスに起因する疾患の治療標的として有望であることも示した。
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