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Investigation of lipid associated alpha-synuclein metabolism

Research Project

Project/Area Number 15K09319
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurology
Research InstitutionKyoto 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)

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)
Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
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)
Keywordsα-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.

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。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (13 results)

All 2019 2018 2017 2016

All Journal Article (11 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 6 results,  Open Access: 6 results,  Acknowledgement Compliant: 2 results) Presentation (2 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Plasma neurofilament light chain: A potential prognostic biomarker of dementia in adult Down syndrome patients2019

    • Author(s)
      Shinomoto Makiko、Kasai Takashi、Tatebe Harutsugu、Kondo Masaki、Ohmichi Takuma、Morimoto Masafumi、Chiyonobu Tomohiro、Terada Naoto、Allsop David、Yokota Isao、Mizuno Toshiki、Tokuda Takahiko
    • Journal Title

      PLOS ONE

      Volume: 14 Issue: 4 Pages: e0211575-e0211575

    • DOI

      10.1371/journal.pone.0211575

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Biomarker repurposing: Therapeutic drug monitoring of serum theophylline offers a potential diagnostic biomarker of Parkinson’s disease2018

    • Author(s)
      Ohmichi Takuma、Kasai Takashi、Kosaka Tadashi、Shikata Keisuke、Tatebe Harutsugu、Ishii Ryotaro、Shinomoto Makiko、Mizuno Toshiki、Tokuda Takahiko
    • Journal Title

      PLOS ONE

      Volume: 13 Issue: 7 Pages: e0201260-e0201260

    • DOI

      10.1371/journal.pone.0201260

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] PDの認知機能障害と関連するバイオマーカー2018

    • Author(s)
      笠井高士、徳田隆彦
    • Journal Title

      認知症の最新医療

      Volume: 8 Pages: 23-28

    • Related Report
      2017 Research-status Report
  • [Journal Article] 認知症と糖尿病2018

    • Author(s)
      笠井高士
    • Journal Title

      京都府立医大雑誌

      Volume: 126 Pages: 697-784

    • Related Report
      2017 Research-status Report
  • [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.
    • Journal Title

      Plos One

      Volume: 12 Issue: 11 Pages: e0188802-e0188802

    • DOI

      10.1371/journal.pone.0188802

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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.
    • Journal Title

      npj Parkinson Disease

      Volume: 3 Issue: 1 Pages: 1-3

    • DOI

      10.1038/s41531-017-0014-4

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [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.
    • Journal Title

      Plos One

      Volume: 11 Issue: 4 Pages: e0174630-e0174630

    • DOI

      10.1371/journal.pone.0174630

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Parkinson病の早期診断2017

    • Author(s)
      笠井高士 徳田隆彦
    • Journal Title

      神経内科

      Volume: 86 Pages: 23-29

    • Related Report
      2016 Research-status Report
  • [Journal Article] Parkinson病の生化学的バイオマーカーの標準化2017

    • Author(s)
      笠井高士 徳田隆彦
    • Journal Title

      神経内科

      Volume: 86 Pages: 499-507

    • Related Report
      2016 Research-status Report
  • [Journal Article] Serum Levels of Coenzyme Q10 in Patients with Multiple System Atrophy.2016

    • Author(s)
      Kasai T, Tokuda T, Ohmichi T, Ishii R, Tatebe H, Nakagawa M, Mizuno T
    • Journal Title

      Plos One

      Volume: 11 Issue: 1 Pages: e0147574-e0147574

    • DOI

      10.1371/journal.pone.0147574

    • Related Report
      2016 Research-status Report 2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] パーキンソン病およびパーキンソン症候群のバイオマーカー2016

    • Author(s)
      笠井高士 徳田隆彦
    • Journal Title

      内科

      Volume: 118 Pages: 251-254

    • Related Report
      2016 Research-status Report
  • [Presentation] Serum Levels of Coenzyme Q10 in Patients with Multiple System Atrophy2017

    • Author(s)
      Kasai T.
    • Organizer
      Alzheimer's and Parkinson Disease Congress 2017
    • Place of Presentation
      ウィーン
    • Year and Date
      2017-03-29
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [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
      2017 Research-status Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2020-03-30  

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