Investigation of lipid associated alpha-synuclein metabolism
Project/Area Number |
15K09319
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Neurology
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Research Institution | Kyoto Prefectural University of Medicine |
Principal Investigator |
Kasai Takashi 京都府立医科大学, 医学(系)研究科(研究院), 講師 (70516062)
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Co-Investigator(Kenkyū-buntansha) |
水野 敏樹 京都府立医科大学, 医学(系)研究科(研究院), 教授 (30264782)
大島 洋一 京都府立医科大学, 医学(系)研究科(研究院), 助教 (50516060)
徳田 隆彦 京都府立医科大学, 医学(系)研究科(研究院), 教授 (80242692)
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Project Period (FY) |
2015-04-01 – 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 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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Keywords | α-synuclein / パーキンソン病 / 脂質 / リポ蛋白 / αsynuclein |
Outline of Final Research Achievements |
We postulated a lipid-associated α-synuclein (α-syn) as unknown molecular aspect of α-syn can relate to the α-syn metabolism and PD mechanism. To confirm its presence, we conducted the three independent proteochemical approaches as following. First,α-syn immunoreactivities were observed in fractions with VLDL, LDL, and HDL by size exclusion chromatography. The corresponding lipoprotein fraction collected by ultracentrifugation also contained α-syn. We also developed the method to purify lipid associated α-syn using lipid absorption column as a more convenient technique. Taken all together, lipid-associated α-syn are suggested to be accompanied mainly with HDL fractions containing ApoA1, ApoE, and Apo J.
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Academic Significance and Societal Importance of the Research Achievements |
本研究はパーキンソン病の根本的な病態に関与するαシヌクレインの新しい存在様式を提案するものである。本研究によって明らかにされた脂質分子関連型αシヌクレインの存在は、αシヌクレイン代謝そのものを既存の脂質代謝調節薬によってコントロールできる可能性を支持するものであり、抗パーキンソン病治療開発スキームに新しい視点を加えた。
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Report
(5 results)
Research Products
(13 results)
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[Journal Article] Increased levels of plasma total tau in adult Down syndrome2018
Author(s)
Kasai T, Tatebe H, Kondo M, Ishii R, Ohmichi T, Yeung WTE, Morimoto M, Chiyonobu T, Terada N, Allsop D, Nakagawa M, Mizuno T, Tokuda T.
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Journal Title
Plos One
Volume: 12
Issue: 11
Pages: e0188802-e0188802
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Early-onset parkinsonism in a pedigree with phosphoglycerate kinase deficiency and a heterozygous carrier: Do PGK-1 mutations contribute to vulnerability to parkinsonism?2017
Author(s)
Sakaue S, Kasai T, Osone S, Azuma Y, Imamura T, Mizuta I, Tokuda T, Kanno H, El-Agnaf OM, Morimoto M, Hosoi H, Mizuno T.
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Journal Title
npj Parkinson Disease
Volume: 3
Issue: 1
Pages: 1-3
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Abeta levels in the jugular vein and high molecular weight Abeta oligomer levels in CSF can be used as biomarkers to indicate the anti-amyloid effect of IVIg for Alzheimer's disease.2017
Author(s)
Kasai T, Kondo M, Ishii R, Tanaka A, Ataka S, Shimada H, Tomiyama T, Mori H, Taylor M, Allsop D, Nakagawa M, Mizuno T, Tokuda T.
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Journal Title
Plos One
Volume: 11
Issue: 4
Pages: e0174630-e0174630
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Early-onset parkinsonism in a pedigree with phosphoglycerate kinase deficiency and a heterozygous carrier: Do PGK-1 mutations contribute to vulnerability to parkinsonism?2017
Author(s)
Takashi Kasai, Satoshi Sakaue, Ikuko Mizuta, Masaya Suematsu, Shinya Osone, Yumiko Azuma, Toshihiko Imamura, Takahiko Tokuda, Hitoshi Kanno, Omar M. A. El-Agnaf, Masafumi Morimoto, Masanori Nakagawa, Hajime Hosoi, and Toshiki Mizuno
Organizer
World Congress of Neurology
Related Report
Int'l Joint Research