Clarification of the pathogenesis of multiple system atrophy and its treatment strategy using AMBRA1
| Project/Area Number |
16K19503
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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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 |
MIKI YASUO 弘前大学, 医学研究科, 助教 (30709142)
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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 |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | AMBRA1 / オートファジー / 多系統萎縮症 / シヌクレイノパチー / αシヌクレイン |
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| Outline of Final Research Achievements |
The accumulation of abnormal α-synuclein is the histopathological feature of multiple system atrophy (MSA). Autophagy is regulated by various proteins including autophagy/beclin1 regulator 1 (AMBRA1). We conducted the present study to elucidate the role of AMBRA1 in the pathogenesis of MSA.
Pathological and biochemical analyses using human brain samples revealed that AMBRA1 is a component of the pathological hallmarks of MSA. A 9-fold stronger affinity was found in AMBRA1 with abnormal α-synuclein compared with non-phosphorylated α-synuclein. Significant correlation between AMBRA1 overexpression and reduction of abnormal α-synuclein was observed. AMBRA1 overexpression or knockdown significantly changed α-synuclein in the mammalian cells.
Our results demonstrated that molecular modulation targeting AMBRA1 can be a promising candidate for the treatment of MSA.
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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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