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Involvement of endogenous N-methyl(R)salsolinol in Parkinson’s disease: induction of apoptosis and protection by (-)deprenyl

  • Conference paper
Advances in Research on Neurodegeneration

Summary

An endogenous dopamine-derived N-methyl(R)salsolinol has been suggested to be involved in the pathogenesis of Parkinson’s disease. In Parkinson’s disease, the level of N-methyl(R)salsolinol increased in cerebrospinal fluid and the high activity of a synthesizing enzyme, (R)salsolinol Nmethyltransferase, was detected in lymphocytes. This isoquinoline induced apoptotic DNA damage in human dopaminergic neuroblastoma SH-SY5Y cells. Among catechol isoquinolines, only N-methylsalsolinol induced apoptosis in the cells, and the scavengers of hydroxyl radicals and antioxidants suppressed DNA damage, suggesting that reactive oxygen species initiate apoptosis. The isoquinoline activated caspase-3 like proteases and a caspase-3 inhibitor protected the cells from DNA damage. (-)Deprenyl, but neither clorgyline nor pargyline, prevented apoptotic cell death. The mechanism of the protection was due to stabilization of mitochondrial membrane potential reduced by the toxin. In Parkinson’s disease apoptosis may be induced in dopamine neurons by this endogenous neurotoxin, and (-)deprenyl may protect them from apoptotic death process.

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Author information

Authors and Affiliations

  1. Department of Brain Sciences, Institute of Applied Biochemistry, Yagi Memorial Park, Mitake, Gifu, 505-0116, Japan

    Dr. M. Naoi

  2. Department of Basic Gerontology, National Institute for Longevity Sciences, Laboratory of Biochemistry and Metabolism, Obu, Aichi, Japan

    W. Maruyama

  3. Department of Food and Nutrition, Aichi-Konan College, Konan, Aichi, Japan

    T. Takahashi

  4. Gifu International Institute of Biotechnology, Mitake, Gifu, Japan

    Y. Akao

  5. The Second Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka, Japan

    Y. Nakagawa

Authors
  1. Dr. M. Naoi
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  2. W. Maruyama
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  3. T. Takahashi
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  4. Y. Akao
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  5. Y. Nakagawa
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Editor information

Editors and Affiliations

  1. Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan

    Y. Mizuno

  2. Neurodegenerative Disorders Centre, Faculty of Medicine, University Hospital, Vancouver, B.C., Canada

    D. B. Calne

  3. Clinical Research, Schering AG, Berlin, Federal Republic of Germany

    R. Horowski

  4. Department of Neurology, University of Innsbruck, Austria

    W. Poewe

  5. Department of Psychiatry, University of Würzburg, Federal Republic of Germany

    P. Riederer

  6. Rappaport Family Institute for Research in the Medical Sciences, Haifa, Israel

    M. B. H. Youdim

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© 2000 Springer-Verlag Wien

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Naoi, M., Maruyama, W., Takahashi, T., Akao, Y., Nakagawa, Y. (2000). Involvement of endogenous N-methyl(R)salsolinol in Parkinson’s disease: induction of apoptosis and protection by (-)deprenyl. In: Mizuno, Y., Calne, D.B., Horowski, R., Poewe, W., Riederer, P., Youdim, M.B.H. (eds) Advances in Research on Neurodegeneration. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6284-2_9

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  • DOI: https://doi.org/10.1007/978-3-7091-6284-2_9

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-7091-7246-9

  • Online ISBN: 978-3-7091-6284-2

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