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The mechanisms of Parkinson's disease. Toxicity of Homocysteine and Genetic Polymorphism of Homocysteine-related enzymes

Research Project

Project/Area Number 13670644
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

NAKASHIMA Kenji  Tottori University, Department of Neusology, Institute of Neurological Sciences (Professor), 医学部, 教授 (70144673)

Co-Investigator(Kenkyū-buntansha) NAKASO Kazuhiro  Tottori University, Department of Neusology, Institute of Neurological Sciences (Clinical and Research fellow), 医学部附属病院, 医員
KOWA Hisanori  Tottori University, Department of Neusology, Institute of Neurological Sciences (Assistant Professor), 医学部附属病院, 助手 (30284003)
YASUI Kenichi  Tottori University, Department of Neusology, Institute of Neurological Sciences (Clinical and Research fellow)
安井 建一  鳥取大学, 医学部・付属病院, 医員
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2001: ¥2,500,000 (Direct Cost: ¥2,500,000)
KeywordsParkinson' s disease / homocysteine / methylentetrahydrofolate reductase / L-dopa / s-adenosylmethionine / s-adenosylhomocysteine / atherosclerosis / wearing-off phenomenone / s-アデノシルメチオニン / wearing-off
Research Abstract

We previously reported that the hyperhomocysteinemia was observed in patients with Parkinson's disease(PD). In this project, to clarify the mechanisms how hyperhomocysteinemia occurs in PD patients, we measured plasma homocysteine level in 20 de novo PD patients in each type of MTHFR C677T genotype before and after levodopa administration. Hcy concentrations before levodopa administration in the 20 de novo PD patients (11.0^^+__-4.5 nmol/ml) did not differ significantly as compared to control subjects (10.2^^+__-5.3 nmol/ml). However, Hcy concentrations were significantly elevated after levodopa administration(18.8^^+__-13.5 nmol/ml). In order to investigate the association between the increase in Hcy concentrations following levodopa treatment and MTHFR C677T genotype, we classified patients into three groups according to their MTHFR genotypes. Hcy concentrations were increased from 10.9^^+__-1.6 to 14.6^^+__-2.4 nmol/ml in the C/C genotype group, from 10.3^^+__-4.0 to 14.1^^+__-4.2 nmol/ml in the C/T group, and from 11.9^^+__-7.1 to 29.3^^+__-21.8 nmol/ml in the T/T group. Moreover, we investigate atheroscrlrotic change in carotid artery in PD patients, because Hcy is one of the risk factors of vascular diseases. Ultrasonography showed hypertrophy of IMC in levodopa treated PD patients. These results suggest that levodopa-induced hyperhomocysteinemia may induce secondary atherosclerosis. Furthermore, we measured S-adenosylmethionine(SAM) and S-adenosylhomocysteine(SAH), metabolites during the formation of Hcy. PD patients treated for long duration or with wearing-off phenomenon have low SAM/SAH ratio.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] Kazuhiro Nakaso et al.: "Hypertrophy of IMC of carotid artery in Parkinson's disease is associated with L-DOPA, homocysteine, and MTHFR genotype"J Neurol Sci. 207. 19-23 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kenichi Yasui et al.: "Levodopa-induced hyperhomocysteinemia in Parkinson's disease"Acta Neurol Sca. (in press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yasui,K., et al.: "Plasma homocysteine and MTHFR genotype in levodopa-treated patients with PD"Neurology. 56. 281-281 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakaso,K., et al.: "Hypertrophy of IMC of carotid artery in Parkinson's disease is associated with L-DOPA, homocysteine, and MTHFR genotype"J Neurol Sci. 207. 19-23 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yasui,K., et. Al.: "Levodopa-induced hyperhomocysteinaemia in Parkinson's disease"Acta Neurol Scand, (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kazuhiro Nakaso et al.: "Hypertrophy of IMC of carotid artery in Parkinson's disease is associated with L-DOPA, homocysteine, and MTHFR genotype"J Neurol Sci. 207. 19-23 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kenichi Yasui et al.: "Levodopa-induced hyperhomocysteinemia in Parkinson's disease"Acta Neurol Sea. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kenichi Yasui et al.: "Plasma homocysteine and MTHFR C677T genotype in levodopa-treated patients with PD"Neurology. 56. 281 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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