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2003 Fiscal Year Final Research Report Summary

Functional and dynamic gene expression profiling of polyglutamine

Research Project

Project/Area Number 14370213
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionTokyo Medical and Dental University (2003)
Tokyo Metropolitan Organization for Medical Research (2002)

Principal Investigator

OKAZAWA Hitoshi  Tokyo Medical and Dental University, Medical Research institute, Professor, 難治疾患研究所, 教授 (50261996)

Co-Investigator(Kenkyū-buntansha) KANAZAWA Ichiro  National Center for Psychiatry and neurology, DEAN, 総長 (30110498)
Project Period (FY) 2002 – 2003
KeywordsPOLYGLUTAMINE DISEASES / MEURODEGENTATION / PQBP-1 / TRANSCRIPTION / NUCLEARFUNCTION / RNA POLYMERASE II
Research Abstract

Polyglutamine diseases are caused by abnormal proteins containing an elongated polyglutamine tract sequence. It is generally believed that aggregation of the mutant proteins is essential for the pathology. However, molecular events induced by abnormal proteins during aggregation process are not fully elucidated. In this project, we applied genomics and proteomics to this question and investigated which genes and proteins are affected in expression. In brief, we found that different disease genes cause different gene and protein expression changes in a neuron type-specific manner. During the process, we found novel modifier genes of polyglutamine disease pathology, which could be used for the future development of molecular therapeutics.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Hoshino M. et al.: "Histone deacetylase activity is retained in primary neurons expressing mutant huntingtin protein."Journal of Neurochemistry. 87. 257-267 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Busch A. et al.: "Mutant huntingtin promotes the fibriollogenesis of wild-type huntingtin : a potential mechanism for loss of huntigtin funtion in Huntington's disease."Journal of Biological Chemistry. 278. 41452-41461 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Okuda T. et al.: "PQBP-1 transgenic mice show a late-onset motor neuron disease phenotype."Human Molecular Genetics. 12. 711-725 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Okazawa H.: "Polyglutamine disease : a transcription disorder?"Cellular Molecular Life Sciences. 60. 1427-1439 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ueda H., Goto J., Hashida H., Lin X., Gyanagi K., Kawano H., Zoghbi H.Y, Kanazawa, I., Okazawa H.: "Enhanced SUMOylation in polyglutamine diseases."Biochem. Biophys. Res. Commun.. 293. 307-313 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Okazawa H., Rich T., Chang A., Lin X., Waragai M., Kajikawa M., Enokido Y, Komuo A., Kato S.Shibata M., Hatanaka H., Mouradian M.M., Sudol M., Kanazawa I.: "Interaction between mutant ataxin-1 and PQBP-1 affects transcription and cell death."Neuron. 34. 701-703 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Enokido Y., Maruoka H., Hatanaka H., Kanazawa I., Okazawa H.: "PQBP-1 increases vulnerability to low potassium stress and represses transcription in primary cerebellar neurons."Biochem. Biophys. Res. Commun.. 294. 268-271 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Okuda T., Hattori H., Takeuchi S., Shimizu J., Ueda H., Palvimo J.J., Kanazawa I., Kawano H., Nakagawa M., Okazawa H.: "PQBP-1 transgenic mice show a late-onset motor neuron disease phenotype."Human Molecular Genetics. 12. 711-725 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Busch A, Engemann S, Lurz R, Okazawa H, Lehrach H, Wanker EE.: "Mutant huntingtin promotes the fibrillogenesis of wild-type huntingtin: a potential mechanism for loss of huntingtin function in Huntington's disease."J Biol Chem.. 278. 41452-41461 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hoshino M, Tagawa K, Okuda T, Murata M, Oyanagi K, Arai N, Mizutani T, Kanazawa I, Wanker EE, Okazawa H: "Histone deacetylase activity is retained in primary neurons expressing mutant huntingtin protein."J. Neurochem.. 87. 257-267 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hoshino M, Tagawa K, Okuda T, Ueda H, Okazawa H: "General transcriptional repression by polyglutamine disease proteins is not directly linked to the presence of inclusion bodies."Biochem. Biophys. Res. Commun.. 313. 110-116 (2004)

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      「研究成果報告書概要(欧文)」より
  • [Publications] Tagawa K, Hoshino M, Okuda T, Ueda H, Hayashi H, Engemann S, Okado H, Ichikawa M, Wanker EE, Okazawa H: "Distinct aggregation and cell death patterns among different types of primary neurons induced by mutant huntingtin protein"J. Neurochem.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2005-04-19  

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