Visualization of dendritic spine: Implication for neurodegenerative dementia
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 |
Research Field |
Neurology
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Research Institution | Hirosaki University |
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 |
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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Report
(3 results)
Research Products
(14 results)
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[Journal Article] AMBRA1, a novel alpha-synuclein-binding protein, is implicated in the pathogenesis of multiple system atrophy.2017
Author(s)
Miki Y, Tanji K, Mori F, Tatara Y, Utsumi J, Sasaki H, Kakita A, Takahashi H, Fimia GM, Wakabayashi K.
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Journal Title
Brain Pathol
Volume: 印刷中
Issue: 1
Pages: 28-42
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Neuropathology of PARK14 is identical to idiopathic Parkinson's disease2017
Author(s)
Miki Y, Yoshizawa T, Morohashi S, Seino Y, Kijima H, Shoji M, Mori A, Yamashita C, Hatano T, Hattori N, Wakabayashi K
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Journal Title
Mov Disord
Volume: -
Issue: 5
Pages: 35-35
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Alteration of Upstream Autophagy-Related Proteins (ULK1, ULK2, Beclin1, VPS34 and AMBRA1) in Lewy Body Disease2016
Author(s)
Miki Y, Tanji K, Mori F, Utsumi J, Sasaki H, Kakita A, Takahashi H, Wakabayashi K.
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Journal Title
Brain Pathol
Volume: -
Issue: 3
Pages: 359-370
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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