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Research for the Parkinson's disease related proteins using endogenous neurotoxins

Research Project

Project/Area Number 12480231
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionHIROSHIMA UNIVERSITY

Principal Investigator

OHTA Shigeru  Hiroshima University, School of Medicine, Professor, 医学部, 教授 (60160503)

Co-Investigator(Kenkyū-buntansha) SUGIHARA Kazumi  Hiroshima Univ., School of Med., Research Associate, 医学部, 教務員 (20271067)
KITAMURA Shigeyuki  Hiroshima Univ., School of Med., Associate Prof., 医学部, 助教授 (40136057)
YOSHIHARA Shinichi  Hiroshima Univ., School of Med., Associate Prof., 医学部, 助教授 (00037607)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥11,100,000 (Direct Cost: ¥11,100,000)
Fiscal Year 2001: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2000: ¥6,800,000 (Direct Cost: ¥6,800,000)
KeywordsParkinson's disease / neurotoxin / differential display / apoptosis / cDNA microaray / テトラハイドロイソキノリン / NMDAレセプター / アポトーシス / テトラヒドロイソキノリン / パーキンソン病防御物質 / パーキンソン病発症物質 / ドーパミン神経 / 細胞培養
Research Abstract

1, 2, 3, 4 -Tetrahydroisoquinoline (TIQ) derivatives, which chemically resemble MPTP, exist in mammals and have been proposed as candidates for endogenous parkinsonogenic compounds, we showed that various TIQ derivatives exist endogenously in animal brain and some of them seem to be related to parkinsonism. TIQ, 1-benzyl-1, 2, 3, 4 -tetrahydroisoquinoline (1BnTIQ) and 1-(3', 4'-dihydroxybenzyl)-1, 2, 3, 4 -tetrahydro-isoquinoline (3', 4' DHBnTIQ) could induce parkinsonism in rodents and a primate. 1BnTIQ existed in cerebrospinal fluid (CSF) of parkinsonian patients at about three times higher levels than in disease controls. Thus these compounds are plausible candidates as Parkinson's disease-inducing substances, but we speculated that other neurotoxins might also be present in the central nervous system.
In this meeting, the mechanism of dopaminergic neuronal cell death by such compounds will be discussed.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] S.Yoshihara: "Metabolism of 1-methy L-4-phenyl 1,2,3,6-tetrahydropyridine(MPTP)in perfused rat liver"Drng Metab. Dispos.. 28. 538-543 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K.Aoyama: "N-Methylation ability for azahetero cyclic amines is nigher in Parkinon's disease : Micotineamide teading test"J. Neurol. Transin.. 107. 985-995 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H.Kawai: "Inhibition of dopamine receptors by endogenous amines : binding to striatel receptors and pharmecological effects"Bioorg. Med. Chem. Lett.. 10. 1669-1771 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H.Kawai: "Dopamine transporter and catechol-O-methyltransferase activities are required for the toxicity of tetrahydroisoquinoline"Chem. Res. Toxicol.. 13. 1294-1301 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] L.Antkiewicz, Michaluk: "Different action on dopamine catabolic pathways of two endogenous 1,2,3,4-tetrahydroisoquinolines"J. Neurochem.. 78. 100-108 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K.Okuda: "Deternin nation of 1-methyl-1,2,3,4-tetrahydroisoquinoline, an endogenous"Life Sci. 70. 1-13 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] S. Yoshihara: "Metabolism of 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydro pyridine (MPTP) in Perfused Rat Liver. Involvement of Hepatic Aldehyde Oxidase as a DetoxificationEnzyme"Drug Metab. Dispos.. 28. 538-543 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K. Aoyama: "N-Methylation ability for azaheterocyclic amines is higher in Parnson's disease : nicotinamideloading test"J. Neural. Transm.. 107. 985-995 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H. Kawai: "Inhibition of dopamine receptors by endogenous amines : binding to striatal receptors and pharmacological effects on locomotor activity"Bioorg. Med. Chem. Lett.. 10. 1669-1771 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H. Kawai: "Dopamine transporter and catechol-O-methyltransferase activities are required for the toxicity of 1-(3', 4'-dihydroxybenzyl)- 1, 2, 3, 4-tetrahydroisoquinoline"Chem. Res. Toxicol. 13. 1294-1301 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] L. Antkiewicz-Michaluk: "Different action on dopamine catabolic pathways of two endogenous 1, 2, 3, 4 -tetrahydroisoquinolines with similar antidopaminergic properties"J. Neurochem.. 78. 100-1-8 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K. Okuda: "Determination method of 1-methyl-1, 2, 3, 4-tetrahydro isoquinoline and endogenous parkinsonism-preventing substance, by radioimmunoassay"Life Sci.. 70. 1-13 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H.Kawai, Y.Kotake, S.Ohta: "Dopamine transporter and catechol-O-methyltransferase activities are required for the toxicity of 3', 4'DHBnTIQ"Chem.Res.Toxicol.. 13. 1294-1301 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] H.Kawai, Y.Kotake, S.Ohta: "Inhibition of dopamine receptors by endogenous amines : binding to striatal receptors and pharmacological effects on locomotor activity"Bioorg.Med.Chem.Lett.. 10. 1669-1771 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] S.Yoshihara, K.Harada, S.Ohta.: "Metabolism of 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) in Perfused Rat Liver : Involvement of Hepatic Aldehyde Oxidase as a Detoxification Enzyme"Drug Metab.Dispos.. 28. 538-543 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] K.Aoyama, K.Matsubara, K.Okada, S.Ohta et al.: "N-Methylation ability for azaheterocyclic amines is higher in Parkinson's disease : nicotinamide loading test"J.Neural.Transm.. 107. 985-995 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] L.Antkiewicz-Michaluk, J.Michaluk, S.Ohata et al.: "Different action on dopamine catabolic pathways of two endogenous 1, 2, 3, 4-tetrahydroisoquinoines with similar antidopaminergic properties"J.Neurochem.. 78. 1001-1008 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] K.Okuda, Y.Kotake, S.Ohta: "Determination method of 1-methyl-1, 2, 3, 4-tetrahydroisoquinoline, an endogenous parkinsonism-preventing substance, by radioimmunoassay"Life Sci.. 70. 1-13 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] H.Kawai,: "Dopamine transporter and catechol-O-methyltransferase activities are required for the toxicity of 1-(3',4'-dihydroxybenzyl)-1,2,3,4-tetrahydroisoquinoline."Chem.Res.Toxicol.. 13. 1294-1301 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] H.Kawai,: "Inhibition of dopamine receptors by endogenous amines : binding to striatal receptors and pharmacological effects on locomotor activity."Bioorg.Med.Chem.Lett.. 10. 1669-1771 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] S.Yoshihara,: "Metabolism of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in Perfused Rat Liver. Involvement of Hepatic Aldehyde Oxidase as a Detoxification Enzyme."Drug Metab.Dispos.. 28. 538-543 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] K.Aoyama,: "N-Methylation ability for azaheterocyclic amines is higher in Parkinson's disease : nicotinamide loading test."J.Neural.Transm.. 107. 985-995 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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