| Project/Area Number |
16K15473
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Neurology
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| Research Institution | Hirosaki University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
丹治 邦和 弘前大学, 医学研究科, 助教 (10271800)
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| Research Collaborator |
MIKI Yasuo 弘前大学, 大学院医学研究科, 助教 (30709142)
MORI Fumiaki 弘前大学, 大学院医学研究科, 准教授 (60200383)
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | シナプス蛋白 / 神経変性 / レビー小体病 / パーキンソン病 / 多系統萎縮症 / シヌクレイン / オートファジー / シナプス / 認知症 / 神経変性疾患 / 神経科学 |
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| Outline of Final Research Achievements |
We have shown that autophagy was dysregulated in patients with alpha-synucleinopathy [Parkinson’s disease (PD), dementia with Lewy bodies and multiple system atrophy (MSA)]. Therefore, we elucidated the role of upstream proteins of autophagy in the pathogenesis of MSA. Our results demonstrated that AMBRA1 is a novel hub binding protein of alpha-synuclein and plays a central role in the pathogenesis of MSA through the degradative dynamics of alpha-synuclein. These results raise the possibility that molecular modulation targeting AMBRA1 can be a promising candidate for the treatment of alpha-synucleinopathy. We further performed whole transcriptome assay by microarray, quantitative RT-PCR and Western blot analysis using peripheral blood mononuclear cells (PBMCs) of patients with PD and age-matched controls. We provided evidence that autophagy in PBMCs could detect a feature confirmed by neuropathology of PD and this alteration of autophagy is a fundamental aspect of PD.
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