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Oligodendrocytic protein contribute to neuronal accumulation of alpha-synuclein in multiple system atrophy

Research Project

Project/Area Number 25830045
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Nerve anatomy/Neuropathology
Research InstitutionInstitute for Developmental Research, Aichi Human Service Center (2014)
National Center for Geriatrics and Gerontology (2013)

Principal Investigator

SUZUKI Yasuyo  愛知県心身障害者コロニー発達障害研究所, 遺伝学部, 研究員 (60416188)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsα-synuclein / 神経変性疾患 / 多系統萎縮症 / 神経科学 / 多系統委縮症 / シスタチンC
Outline of Final Research Achievements

Multiple system atrophy (MSA) is a neurodegenerative disease in which oligodendrocytes and neurons in the central nervous system are affected. To clarify how oligodendrocytic α-synuclein inclusions cause neuronal degeneration, we generated a transgenic mouse for an MSA model in which human wild-type α-synuclein was overexpressed selectively in oligodendrocytes. We established primary culture cells derived from the brain of transgenic mice, and revealed that insoluble mouse α-synuclein was progressively accumulated in neurons, leading to neuronal dysfunction and degeneration. In this study, we identified cystatin C as a neurodegeneration-inducing factor released from oligodendrocytes. Cystatin C triggers insoluble α-synuclein accumulation in neurons of the mouse central nervous system.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (6 results)

All 2014 2013 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Acknowledgement Compliant: 1 results) Presentation (2 results) Remarks (1 results)

  • [Journal Article] beta-III Tubulin fragments inhibit alpha-synuclein accumulation in models of multiple system atrophy.2014

    • Author(s)
      Yasuyo Suzuki, Chenghua Jin, Tamaki Iwase, Ikuru Yazawa
    • Journal Title

      Journal of Biological Chemistry

      Volume: 289 Issue: 35 Pages: 24374-24382

    • DOI

      10.1074/jbc.m114.557215

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Cystatin C triggers neuronal degeneration in a model of multiple system atrophy.2014

    • Author(s)
      Suzuki, Y., Jin, C., and Yazawa, I
    • Journal Title

      American Journal of Pathology

      Volume: 184 Issue: 3 Pages: 790-799

    • DOI

      10.1016/j.ajpath.2013.11.018

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Increased aggregation of polyleucine compared with that of polyglutamine in dentatorubral-pallidoluysian atrophy protein.2013

    • Author(s)
      Suzuki Y, Jin C, Yazawa I.
    • Journal Title

      Neuroscience Letters

      Volume: 552 Pages: 156-161

    • DOI

      10.1016/j.neulet.2013.07.043

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 多系統萎縮症におけるオリゴデンドロサイト由来シスタチンCが神経細胞のα-synuclein蓄積を誘導する2014

    • Author(s)
      鈴木 康予,金 成花,矢澤 生
    • Organizer
      第37回日本神経科学大会
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Year and Date
      2014-09-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] 多系統萎縮症におけるオリゴデンドロサイト封入体形成の神経細胞への影響2013

    • Author(s)
      鈴木康予,都竹佳子,矢澤生
    • Organizer
      Neuro2013(第36回日本神経科学大会,第56回日本神経化学会大会,第23回日本神経回路学会大会 合同大会)
    • Place of Presentation
      国立京都国際会館(京都)
    • Related Report
      2013 Research-status Report
  • [Remarks] 国立長寿医療研究センター バイオリソース研究室

    • URL

      http://www.ncgg.go.jp/department/lrr/LoRRe.htm

    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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