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2003 Fiscal Year Final Research Report Summary

Research on the factor causing indivisual fifference Parkinson's disease

Research Project

Project/Area Number 14570603
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

NOMOTO Masaniro  Ehime University, School of Medicine, Professor, 医学部, 教授 (50208401)

Co-Investigator(Kenkyū-buntansha) MIKI Tetsuro  Ehime University, School of Medicine, Professor, 医学部, 教授 (00174003)
OHASHI Kyouichi  Hamamatsu Medical University, School of Medicine, Professor, 医学部・臨床薬理学, 教授 (20137714)
Project Period (FY) 2002 – 2003
KeywordsParkinson's disease / L-dopa / Pharmacokinetics / Transporters / polymorphism / CYP / dopamine receptor agonist / drug interaction
Research Abstract

There has been significant progress in the study of the causes, the pathogenesis, and the mechanism of cell death in Parkinson's disease (PD). Mutations in single genes have been shown to cause PD, and accumulation of alpha-synuclein seems to be a clue to the pathogenesis of neurodegeneration. However, mutations of single genes account for only a small number of cases. Environmental factors seem to play a large role in the majority of cases of sporadic PD. Genetic factors may predispose patients to develop PD if combined with other gene mutations or environmental toxins. In an attempt to design a neuroprotective therapy, the pathogenesis of neurodegeneration, and the mechanism of cell death have been studied. Aggregation of insoluble alpha-syuclein, oxidant stress, mitochondrial dysfunction, excitotoxicity, and glia and inflammatory processes are all thought to contribute to the cell death process and agents that interfere with these events may be neuroprotective. The final culmination of these events is supposed to be the induction of apoptosis in nigral dopaminergic neurons and this too offers opportunities for providing neuroprotection. A large number of different approaches are under discussion in the hope of developing a neuroprotective therapy, using clinical indices and neuroimaging markers of nigral dopaminergic neurons. Administration of L-dopa and other antiparkinsonian agents reverse motor deficits of patients with Parkinson s disease, however, the response to the treatment varies depend on each individual patient. We studied pharmacokinetics of medicines and their effect on parkinsonian signs, and grouped patients through their characteristic reactions to the treatment. They are now studied on the polymorphism of transpoters at the intestine, the neuron or the kidney. These results will be compared with those of superhelthy persons with the age of more than 100, to find the key gene to cause Parkinson's disease.

  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Oyoshi T, Nomoto M et al.: "Pathodynamics of nitric oxide production within implanted glioma studied with an in vivo microdialysis technique and immunohistochemistry."J Pharmacol Sci. 91. 15-22 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nomoto M.: "Clinical pharmacology and neuroprotection in Parkinson's disease."Parkinsonism & Related Disorders. 9 Suppl 2. 55-58 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Jie Zhang, Fu-rong Qu, Nakatsuka A, Nomura T, Nagai M, Nomoto M.: "Pharmacokinetics of L-dopa in Plasma and Extracellular Fluid of Striatum In common Marmosets."Brain Research. 993. 54-58 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nagai M, Osame M.: "Human T-cell lymphotropic virus type I and neurological diseases."Journal of Neurovirology. 2. 228-235 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tomaru U, Yamano Y, Nagai M, Maric D, Kaumaya PT, Biddison W, Jacobson S.: "Detection of virus-specific T cells and CD8(+) T-cell epitopes by acquisition of peptide-HLA-GFP complexes : analysis of T-cell phenotype and function in chronic viral infections."Nature Medicine. 9. 469-476 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Iwata S, Nomoto M, Morioka M, Miyata A.: "Gene expression profiling in the midbrain of striatal 6-hydroxydopamine-injected mice."Synapse. 51(4). 279-286 (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Saito M, Nakagawa M, Kaseda S, Matsuzaki T, Jonosono M, Eiraku N, Kubota R, Takenouchi N, Nagai M, Furukawa Y, Usuku K, Izumo S.: "Decreased Human T Lymphotropic Virus Type I (HTLV-I) provirus Load and alteration in T Cell phenotype after interferon-alpha therapy for HTLV-I-associated myelopathy/Tropical spastic paraparesis."Journal of Infectious Diseases. 189(1). 29-40 (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Maloney EM, Nagai M, Hisada M, Soldan SS, Goebel PB, Carrington M, Sawada T, Brennan MB, Cranston B, Hanchard B, Jacobson S.: "Prediagnostic Human T Lymphotropic Virus Type I provirus loads were highest in Jamaican children who developed seborrheic dermatitis and severe anemia."Journal of Infectious Diseases. 189(1). 41-45 (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 野元正弘: "抗パーキンソン病薬の薬理作用と特徴"神経治療学. 19. 11-20 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 野村拓夫, 野元正弘: "錐体外路性不随意運動の鑑別疾患と発現メカニズム-ジスキネジア-"Clinical Neuroscience. 20. 1282-1286 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 張捷, 中塚晶子, 野村拓夫, 野元正弘: "創薬におけるコモン・マーモセットの応用"愛媛医学. 21. 273-277 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 野村拓夫, 中塚晶子, 張捷, 野元正弘: "Bromocriptin投与中に大量の胸水貯留を呈したパーキンソン病の1例"運動障害. 12. 101-107 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 中塚晶子, 野村拓夫, 野元正弘: "薬剤による神経症状"内科. 91(4). 695-702 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 中塚晶子, 野元正弘: "抗パーキンソン病薬の種類とその特徴"日本内科学会雑誌. 92(8). 29-35 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 永井将弘, 野元正弘: "薬物による痴呆-消化器官作用薬-"痴呆症学(2)日本臨床. 62(S1). 498-502 (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 永井将弘, 野元正弘: "MAO阻害薬およびCOMT阻害薬"脳の科学-パーキンソン病のすべて-. 26(292). 297-301 (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Oyoshi T, Nomoto M et al.: "Pathodynamics of nitric oxide production within implanted glioma studied with an in vivo microdialysis technique and immunohistochemistry."J Pharmacol Sci. 91. 15-22 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nomoto M.: "Clinical pharmacology and neuroprotection in Parkinson's disease."Parkinsonism & Related Disorders. 9(Suppl 2). 55-58 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Jie Zhang, Fu-rong Qu, NakatsukaNomura T, Nagai M, Nomoto M.: "Pharmacokinetics of L-dopa in Plasma and Extracellular Fluid of Striatum In common Marmosets."Brain Research. 993. 54-58 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nagai M, Osame M.: "Human T-cell lymphotropic virus type I and neurological diseases."Journal of Neurovirology. 2. 228-235 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tomaru U, Yamano Y, Nagai M, Maric D, Kaumaya PT, Biddison W, Jacobson S.: "Detection of virus-specific T cells and CD8(+ )T-cell epitopes by acquisition of peptide -HLA-GFP complexes : analysis of T-cell phenotype and function in chronic viral infections."Nature Medicine. 9. 469-476 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Iwata S, Noraoto M, Morioka M, Miyata A.: "Gene expression profiling in the midbrain of striatal 6-hydroxydopamine-injected mice."Synapse. 54(1). 279-286 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Saito M, Nakagawa M, Kaseda S, Matsuzaki T, Jonosono M, Eiraku N, Kubota R, Takenouchi N, Nagai M, Furukawa Y, Usuku K, Izumo S.: "Decreased Human T Lymphotropic Virus Type I (HTLV-I) provirus Load and alteration in T Cell phenotype after interferon-alpha therapy for HTLV-I-associated myelopathy/Tropical spastic paraparesis."Journal of Infectious Diseases. 189(1). 29-40 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Maloney EM, Nagai M, Hisada M, Soldan SS, Goebel PB, Carrington M, Sawada T, Brennan MB, Cranston B, Hanchard B, Jacobson S.: "Prediagnostic Human T Lymphotropic Virus Type I provirus loads were highest in Jamaican children who developed seborrheic dermatitis and severe anemia."Journal of Infectious Diseases. 189(1). 41-45 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nomoto M.: "Drug for Parkinson's Disease."Neurological Therapeutics. 19. 11-20 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nomura T, Nomoto M.: "Dyskinesia."Clinical Neuroscience. 20. 1282-1286 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Zhang J, Nakatsuka A, Nomura T, Nomoto M.: "Application of the common marmoset for developing new drugs."Ehime Igaku. 21. 273-277 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nomura T, Nakatsuka A, Zhang J, Nomoto M.: "A case of bromocriptine induced massive pleural effusion in a patient with Parkinson's disease."JMDD. 12. 101-107 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakatsuka A, Nomura T, Nomoto M.: "Drug-induced neurological disorders."Naika. 91(4). 695-702 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakatsuka A, Nomoto T.: "Drugs for the treatment of Parkinson's disease."Nihon Naika Gakkai Zasshi. 92(8). 29-35 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nagai M, Nomoto M.: "Neuropsychiatric complications associated with digestive system agents."Nippon Rinsho. 62(S1). 498-502 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nagai M, Nomoto M.: "MAO inhibitor and COMT inhibitor."Brain Science. 26(292). 297-301 (2004)

    • 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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