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Studies on the pathophysiology and gene therapy for adrenoleukodystrophy using knock-out mice

Research Project

Project/Area Number 08457191
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

YAMADA Takeshi  Department of Neurology, Kyushu University, Associate Professor, 医学部, 助教授 (50230462)

Co-Investigator(Kenkyū-buntansha) NAGANO Sukehisa  Department of Neurology, Kyushu University, Resident, 医学部, 医員
FURUYA Hirokazu  Department of Neurology Kyushu University, Lecturer, 医学部, 講師 (60253415)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥7,700,000 (Direct Cost: ¥7,700,000)
Fiscal Year 1997: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1996: ¥6,500,000 (Direct Cost: ¥6,500,000)
Keywordsadrenoleukodystrophy / ALD / ALDP / knockout mice / very long chain fatty acid / beta-oxidation / VLACS / peroxisome / 遺伝子治療 / レトロウイルスベクター
Research Abstract

X-linked adrenoleukodystrophy (ALD) is caused by the mutation of ALD protein (ALDP) gene.Its principal biochemical abnormality is the accumulation of very long chain fatty acids (VLCFA) in tissues and body fluids, due to the impairment of beta-oxidatation in the peroxisome. We clarify its pathophysiology using the ALDP-deficient mice.
VLCFA beta-oxidation in the ALD fibroblasts was not corrected by overxpression of VLACS only but done by overxpression of both VLACS and ALDP.Western blot analysis revealed that the VLACS protein was present in each tissue from the ALDP-deficient mouse. Liver peroxisomes were purified by Nycodenz gradient centrifugation. The VLACS protein was detected only in the peroxisomal fraction from the control mouse, while it was detected in the cytosol fraction as well as the peroxisomal fraction from the ALDP-deficient mouse. These results indicated that ALDP is involved in the transport of VLACS into the peroxisome and that VLACS can not catalyze VLCFA beta-oxidation unless localized in the peroxisome.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] Yamada Takeshi: "Protease inhibitor suppress the degradation of mutant adrenoleuko-dystrophy proteins but do not correct irmpaiment of very long chain fatty acid metabolism in adrenoleukodystrophy fibroblasts" Neurochemical Research. 22. 233-237 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kobayashi Takuro: "Adrenoleukodystrophy protein-deficient mice represent abnormality of very long chain fatty acid metabolism" Biochem Biophys Res Commun. 232. 631-636 (1977)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yamada, T,Shinnoh N,Kobayashi T: "Protease inhibitor suppress the degradarion of mutant adrenoleukodystrophy proteins but do not correct impaiment of very long chain fatty acid metabolism in adrenoleukodystrophy fibroblasts" Neurochemical research. 22. 233-237 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kobayashi T,Shinnoh N,Kondo A,Yamada T: "Adrenoleukodystrophy protein-deficient mice represent abnormality of very long chain fatty acid metabolism" Biochem Biophys Res Commun. 232. 631-636 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yamada Takeshi: "Protease inhibitor suppress the degradation of mutant adrenoleukodystrophy proteins but do not correct impairment of very long chain fatty acid metabolism in adrenoleukodystrophy fibroblasts" Neurochemical Research. 22. 233-237 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kobayashi Takuro: "Adrenoleukodystrophy protein-deficient mice represent abnormality of very long chain fatty acid metabolism" Biochem Biophys Res Commun. 232. 631-636 (1977)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yamada Takeshi: "Protease inhibitors suppress the degradation of mutant adrenoleukodystrophy proteins but do not correct impairment of very long chain fatty acid metabolism in adrenoleukodystrophy fibroblasts" Neurochemical Research. (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Kobayashi Takuro: "Adrenoleukodystrophy protein-deficient mice represent abnormality of very long chain fatty acid metabolism" Biochem.Biophys.Res.Commun.(in press).

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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