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Elucidation of molecular mechanisms and development of surrogate markers for multiple system atrophy caused by COQ2 mutations

Research Project

Project/Area Number 26253054
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionThe University of Tokyo

Principal Investigator

Tsuji Shoji  東京大学, 医学部附属病院, 教授 (70150612)

Co-Investigator(Kenkyū-buntansha) 三井 純  東京大学, 医学部附属病院, 助教 (70579862)
Co-Investigator(Renkei-kenkyūsha) GOTO Jun  東京大学, 医学部附属病院, 准教授 (10211252)
MITSUI Jun  東京大学, 医学部附属病院, 助教 (70579862)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥42,250,000 (Direct Cost: ¥32,500,000、Indirect Cost: ¥9,750,000)
Fiscal Year 2016: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Fiscal Year 2015: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Fiscal Year 2014: ¥27,950,000 (Direct Cost: ¥21,500,000、Indirect Cost: ¥6,450,000)
Keywords多系統萎縮症 / COQ2 / フラックスアナライザー / coenzyme Q10 / ミトコンドリア / 神経分子病態学 / shojitsuji-tky / ミトコンドリア機能
Outline of Final Research Achievements

In our previous studies, we found that COQ2 mutations are associated with familial as well as sporadic multiple system atrophy (MSA). To quantitatively evaluate the altered functions of COQ2 coding for an enzyme in the biosynthesis of CoQ10, we measured oxygen consumption rates (OCR) of yeast harboring mutant human COQ2 cDNA employing a Flux Analyzer. We prepared mutant yeast with a deletion of yeast COQ2 gene. We then transformed the yeast with mutant human COQ2 cDNA, and measured the OCRs of these yeast strains. We demonstrated that OCRs of yeast harboring V393A, a susceptibility variant for sporadic MSA, or M128V, a causative mutation for familial MSA, are significantly decreased. The results suggest that OCR measurement may be utilized as a surrogate marker for MSA.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (3 results)

All 2017 2016

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (2 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Three-year follow-up of high-dose ubiquinol supplementation in a case of familial multiple system atrophy with compound heterozygous COQ2 mutations.2017

    • Author(s)
      Mitsui J, Koguchi K, Momose T, Takahashi M, Matsukawa T, Yasuda T, Tokushige S, Ishiura H, Goto J, Nakazaki S, Kondo T, Ito H, Yamamoto Y and Tsuji S.
    • Journal Title

      Cerebellum

      Volume: - Issue: 3 Pages: 1-9

    • DOI

      10.1007/s12311-017-0846-9

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Functional Analysis of COQ2 V393A variant associated with Multiple system atrophy based on measurement of Oxygen Consumption Rate of Transformed Yeasts Carrying human COQ2 cDNAs.2016

    • Author(s)
      Tsutomu Yasuda, Takashi Matsukawa, Jun Mitsui, Shoji Tsuji
    • Organizer
      International Congress of Human Genetics
    • Place of Presentation
      Kyoto
    • Year and Date
      2016-04-03
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Functional Analysis of COQ2 V393A variant associated with Multiple system atrophy based on measurement of Oxygen Consumption Rate of Transformed Yeasts Carrying human COQ2 cDNAs.2016

    • Author(s)
      Tsutomu Yasuda, Takashi Matsukawa, Jun Mitsui, Shoji Tsuji
    • Organizer
      The 13th International Congress of Human Genetics
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      2016-04-03
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research

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Published: 2014-04-04   Modified: 2018-03-22  

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