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Neurotoxins induce apoptosis in dopamine neurons: protection by N-propargylamine-1(R)- and (S)-aminoindan, rasagiline and TV1022

  • Conference paper
Advances in Research on Neurodegeneration

Summary

In Parkinson’s disease, apoptosis was proposed to cause cell death in nigral dopamine neurons. An endogenous dopaminergic neurotoxin, N-methyl(R)salsolinol, stereo-selectively induced apoptosis in human neuroblastoma SH-SY5Y cells. In this paper the intracellular mechanism of apoptosis was studied using N-methyl(R)salsolinol, 6-hydroxydopamine and peroxynitrite as inducers of apoptosis. Apoptotic cascade was initiated by opening of mitochondrial permeability transition pore, as shown by collapse of mitochondrial membrane potential, AtPm. Apoptosis was executed by caspase 3 activation, followed by DNA fragmentation, which was antagonized by overexpressed Bc1-2. Propargylamines were found to protect the cells from apoptosis, and rasagiline, a selective irreversible inhibitor of type B monoamine oxidase was the most potent to prevent the cell death. Rasagiline preserved O’Pm, which was proved also in isolated mitochondria, and rasagiline completely suppressed the activation of caspases and DNA fragmentation. These results suggest that mitochondria regulate apoptotic process, which may be a target of neuroprotection by rasagiline.

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Authors and Affiliations

  1. Department of Basic Gerontology, National Institute for Longevity Sciences, Aichi, Japan

    W. Maruyama

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

    Y. Akao

  3. Technion-Israel Institute of Technology,Faculty of Medicine, Eve Topf and NPF Centers of Excellence for Neurodegenerative Diseases Research, Haifa, Israel

    M. B.H. Youdim

  4. Department of Brain Sciences, Institute of Applied Biochemistry, Gifu, Japan

    M. Naoi

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  1. W. Maruyama
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  2. Y. Akao
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  3. M. B.H. Youdim
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  4. M. Naoi
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Editor information

Editors and Affiliations

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

    P. Riederer

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

    D. B. Calne

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

    R. Horowski

  4. Department of Neurology, Juntendo University, Tokyo, Japan

    Y. Mizuno

  5. Department of Neurology, Mount Sinai Medical Center, New York, New York, USA

    C. W. Olanow

  6. Department of Neurology, University of Innsbruck, Innsbruck, Austria

    W. Poewe

  7. Department of Pharmacology, Faculty of Medicine, Technion, Haifa, Israel

    M. B. H. Youdim

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© 2000 Springer-Verlag Wien

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Maruyama, W., Akao, Y., Youdim, M.B., Naoi, M. (2000). Neurotoxins induce apoptosis in dopamine neurons: protection by N-propargylamine-1(R)- and (S)-aminoindan, rasagiline and TV1022. In: Riederer, P., et al. Advances in Research on Neurodegeneration. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6301-6_11

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  • DOI: https://doi.org/10.1007/978-3-7091-6301-6_11

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-211-83537-1

  • Online ISBN: 978-3-7091-6301-6

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