2002 Fiscal Year Final Research Report Summary
The mechanisms of Parkinson's disease. Toxicity of Homocysteine and Genetic Polymorphism of Homocysteine-related enzymes
| Project/Area Number |
13670644
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Tottori University |
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Principal Investigator |
NAKASHIMA Kenji Tottori University, Department of Neusology, Institute of Neurological Sciences (Professor), 医学部, 教授 (70144673)
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| 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)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Parkinson' s disease / homocysteine / methylentetrahydrofolate reductase / L-dopa / s-adenosylmethionine / s-adenosylhomocysteine / atherosclerosis / wearing-off phenomenone |
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| 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.
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