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Function of DJ-1, a causative gene for familial Parkinson's disease PARK7

Research Project

Project/Area Number 18390253
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionHokkaido University

Principal Investigator

ARIGA Sanae  Hokkaido University, Res. Fac. of Agri., Professor (90184283)

Co-Investigator(Kenkyū-buntansha) ARIGA Hiroyoshi  Hokkaido University, Grad. School of Phanna. Sci., Professor (20143505)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥17,750,000 (Direct Cost: ¥15,500,000、Indirect Cost: ¥2,250,000)
Fiscal Year 2007: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
Fiscal Year 2006: ¥8,000,000 (Direct Cost: ¥8,000,000)
KeywordsDJ-1 / Parkinson's disease / oxidative stress / mitochondria / tyrosine hydroxylase / reactive oxygen species / oncogene / neurodegeneration disease
Research Abstract

DJ-1 has recently been shown to be responsible for onset of familial Parkinson's disease (PD), PARK7. We have shown that DJ-1 plays roles in transcriptional regulation and anti-oxidative stress, and loss of its function is thought to trigger onset of PD.
(1) A role of DJ-1 in dopamine synthesis.
DJ-1 was found to bind to tyrosine hydroxylase and DOPA decarboxylase and enhance their activities. Mutants found in Parkinson's disease (PD) patients lost its activities. Heterozygous mutants worked as dominant negatives towards wild-type DJ-1, suggesting that heterozygous mutants will be risk factors for onset of PD. After oxidation stresses come to cells, a cysteine residue at 106 (C106) of DJ-1 was oxidized to SOH, SO_2H and SO_3H. When C106 was weakly oxidized with SOH, and SO_2H forms, DJ-1 was activated. When C106 was strongly oxidized with the SO_3H forms, DJ-1 was inactivated. These findings suggest that DJ-1 is committed to onset of a sporadic form of PD.
(2) Pharmaceutical application of DJ-1 and its binding compounds to PD.
Injection of DJ-1 protein into the brain of PD model rats dramatically protected neuronal cell death and locomotive defect. Furthermore, we have identified several compounds that bind to the C106 region of DJ-1 and these compounds also protected neuronal cell death and locomotive defect in PD model rats. These compounds inhibited strong oxidation of C106 of DJ01, thereby keeping active forms of DJ-1.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (16 results)

All 2008 2007 2006

All Journal Article (12 results) (of which Peer Reviewed: 3 results) Presentation (2 results) Book (1 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] DJ-1 protects against neurodegeneration caused by focal cerebral ischemia and reperfusion in rats.2008

    • Author(s)
      Yanagisawa, D.
    • Journal Title

      J. Cereb. Blood. Flow. Metab. 28

      Pages: 563-578

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Secretion of DJ-1 into the serum of patients with Parkinson's disease.2008

    • Author(s)
      Maita, C.
    • Journal Title

      Neuroscience Lett. 431

      Pages: 86-89

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] DJ-1 protects against neurodegeneration caused by focal cerebral ischemia and reperfusion in rats.2008

    • Author(s)
      Yanagisawa, D. , et. al.
    • Journal Title

      J. Cereb. Blood. Flow. Metab. 28

      Pages: 563-578

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Secretion of DJ-1 into the serum of patients with Parkinson's disease.2008

    • Author(s)
      Maita, C., et. al.
    • Journal Title

      Neuroscience Lett. 431

      Pages: 86-89

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] DJ-1 degrades transthyretin and an inactive form of DJ-1 is secreted in familial amyloidotic polyneuropathy.2007

    • Author(s)
      Koide-Yoshida, S
    • Journal Title

      Int. J. Mol. Med. 19

      Pages: 885-894

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] DJ-1 degrades transthyretin and an inactive form of DJ-1 is secreted in familial amyloidotic polyneuropathy.2007

    • Author(s)
      Koide- Yoshida, S. , et. al.
    • Journal Title

      Int. J. Mol. Med. 19

      Pages: 885-894

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Proper SUMO-1 conjugation is essential to DJ-1 to exert its full activities2006

    • Author(s)
      Shinbo, Y.
    • Journal Title

      Cell Death Diff. 13・1

      Pages: 96-108

    • Related Report
      2006 Annual Research Report
  • [Journal Article] DJ-1 interacts with HIPK1 and affects H202-induced cell death2006

    • Author(s)
      Sekito, A.
    • Journal Title

      Free Radic. Res. 40・2

      Pages: 155-165

    • Related Report
      2006 Annual Research Report
  • [Journal Article] PARK7 DJ-1 protects against degeneration of nigral dopaminergic neurons in Parkinson's disease rat model.2006

    • Author(s)
      Inden, M.
    • Journal Title

      Neurobiol. Dis. 24・1

      Pages: 144-158

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Protection against nonylphenol-induced cell death by DJ-1 in cultured Japanese medaka (Oryzias latipes) cells2006

    • Author(s)
      Li, H.M.
    • Journal Title

      Toxicology 228・2-3

      Pages: 229-238

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Establishment of specific antibodies that recognize C106-oxidized DJ-12006

    • Author(s)
      Ooe, H.
    • Journal Title

      Neuroscience Lett. 404・1-2

      Pages: 166-169

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Specific cleavage of DJ-1 under an oxidative condition2006

    • Author(s)
      Ooe, H.
    • Journal Title

      Neuroscience Lett. 406・3

      Pages: 165-168

    • Related Report
      2006 Annual Research Report
  • [Presentation] 酸化ストレス防御タンパク質DJ-1とパーキンソン病2008

    • Author(s)
      有賀寛芳
    • Organizer
      第81回日本薬理学会年会シンポジウム
    • Place of Presentation
      パシフィコ横浜、横浜
    • Year and Date
      2008-03-17
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] DJ-1, a oxidative stress protein, and Parkinson's disease.2008

    • Author(s)
      Ariga, H. , et. al.
    • Organizer
      Symposium in The 81nd Annual meeting of The Japanese Pharmacological Society
    • Place of Presentation
      Pacifico Yokohama, Yokohama
    • Year and Date
      2008-03-17
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] クラーク 分子生物学2008

    • Author(s)
      有賀寛芳
    • Publisher
      丸善
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 神経変性疾患治療薬2006

    • Inventor(s)
      有賀寛芳
    • Industrial Property Rights Holder
      北海道大学
    • Filing Date
      2006-11-28
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Overseas

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Published: 2006-04-01   Modified: 2016-04-21  

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