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2001 Fiscal Year Final Research Report Summary

STRATEGIC RESEARCH FOR POSSIBLE SUPPRESSION OF NEURONAL DEATH BY CASPASE INHIBITORS

Research Project

Project/Area Number 12357004
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Neurology
Research InstitutionThe University of Tokyo

Principal Investigator

KANAZAWA Ichiro  DEPARTMENT OF NEUROLOGY, PROFESSOR, 医学部附属病院, 教授 (30110498)

Co-Investigator(Kenkyū-buntansha) MURATA Miho  DEPARTMENT OF NEUROLOGY, RESEARCH ASSOCIATE, 医学部附属病院, 助手 (30282643)
GOTO Jun  DEPARTMENT OF NEUROLOGY, RESEARCH ASSOCIATE, 医学部附属病院, 助手 (10211252)
KWAK Shin  DEPARTMENT OF NEUROLOGY, ASSOCIATE PROFESSOR, 医学部附属病院, 助教授 (40160981)
MASAYASU Hiroyuki  DAIICHI DRUG COMPANY, GROUP CHIEF (Researcher), 医薬開発企画部, グループ長(研究職)
Project Period (FY) 2000 – 2001
KeywordsCASPASES / CAG REPEAT DISEASES / NEURONAL CELL DEATH / CASPASE INHIBITORS
Research Abstract

Caspases are partly accepted as responsible molecules for neuronal death particularly due to apoptosis. At first, we postulated to suppress neuronal death by inhibition of caspases. However, it was practically difficult to do so mainly because caspase inhibitors are not specific for each substrate. When we investigated the relationship between nuclear morphology and activities of caspases (caspase 1,2,3,6,9) in cultured cells, SHSY5Y, we found a clear discrepancy. In fact, caspase activities were normal even when nuclei were apoptotically segmented. These findings, however, are largely predictable and not novel. Then, we made a plan to suppress the disease process by a different method. Since GAG repeat expansion diseases are caused by the expression of the abnormal gene products, we planned to supress the disease by using a method based on RNAi. This budget was used for the latter project effectively.

  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Yoshizawa T, Yamagishi Y, Koseki N, Goto J, Yoshida H, Shibasaki F, Shoji S, Kanazawa I: "Cell cycle arrest enhances the in vitro cellular toxicity of the truncated Machado-Joseph disease gene product with an expanded polyglutamine stretch"Human Molecular Genetics. 9(1). 69-78 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Wang GH, Sawai N, Kotliarova S, Kanazawa I, Nukina N: "Ataxin-3, the MJD1 gene product, interacts with the two human homologs of yeast DNA repair protein RAD23, HHR23A and HHR23B"Human Molecular Genetics. 9(12). 1795-1803 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hazeki N, Tukamoto I, Goto J, Kanazawa I: "Formic acid dissolves aggregates of an N-terminal Huntingtin fragment containing an expanded polyglutamine tract : appolying to quantification of protein components of the aggregates"Biochemical Biophysical Research Communication. 277. 386-393 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kanazawa I: "How do neurons die in neurodegenerative diseases?"Trends in Molecular Medicine. 7(8). 339-344 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakamura K, Jeong SY, Uchihara T, Anno M, Nagashima K, Nagashima T, Ikeda S, Tsuji S, Kanazawa I: "SCA17, a novel autosomal dominant cerebellar ataxia caused by an expanded polyglutamine in TATA-binding protein"Human Molecular Genetics. 10(14). 1441-1448 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hashida H, Goto J, Suzuki T, Jeong SY, Masuda N, Ooie T, Tachiiri Y, Tsuchiya H, Kanazawa I: "Single cell analysis of CAG repeat in brains of dentatorubral-pallidoluysian atrophy (DRPLA)"Journal of Neurological Sciences. 190. 87-93 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kanazawa I: "Gulutamine Repeats and Neurodegenerative Diseases : Molecular Aspects (Molecular pathology of dentatorubral-pallidoluysian atrophy)"Harper P & Perutz M, Oxford University Press Inc, New York. 249-260 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshizawa T, Yamagishi Y, koseki N, Goto J, Yoshida H, Shibasaki F, Shoji S, Kanazawa I: "Cell cycle arrest enhances the in vitro cellular toxicity of the truncated Machado-Jpseph disease gene product with an expanded polyglutamine stretch"Human Molelular Genetics. 9. 69-78 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Wang GH, Sawai N, Kotliarova S, Kanazawa I, Nukina N: "Ataxin 3, the MJD1 gene product, interacts with the two human homologs of yeast DNA repair protein RAD23, HHR23A and HHR23B"Human Molelular Genetics. 9. 1795-1803 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hazeki N, Tukamoto T, Goto J, Kanazawa I: "Formic acid disolves aggregates of and N-terminal huntingtin fragment containing an expanded polyglutamine tract : applying to quantification of protein components of the aggregates"Biochemical Biophysical Research Cummunications. 277. 386-393 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kanazawa I: "How do neurons die in neurodege-nerative diseases?"Trends in Molelular Medicine. 7. 339-344 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakamura k, Jeong SY, Uchihara T, Anno M, Nagashima K, Nagashima T, Ikeda S, Tsuji S, Kanazawa I: "SCA17, a novel autosomal dominant cerebellar ataxia caused by an expanded polyglutamine in TATA-binding protein"Human Molelular Genetics. 10. 1441-1448 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hashida H, Goto J, Suzuki T, Jeong SY, Masuda N, Ooie T, Tachiiri Y, Tsuchiya H, Kanazawa I: "Single cell analysis of GAG repeat in brains of dentatorubral-pallidoluysian atrophy (DRPLA)"Journal of Neurological Sciences. 190. 87-93 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kanazawa I , edited by Harber P and Peruts M: "Molecular pathology of dentatorubral-pallidoluysian atrophy "Glutamine Repeats and Neurodege-nerative Diseases : Molecular Aspects""Oxford University Press. 249-260 (2001)

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

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Published: 2004-04-14  

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