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Neuroprotection by propargylamines in Parkinson’s disease: intracellular mechanism underlying the anti-apoptotic function and search for clinical markers

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Neuropsychiatric Disorders An Integrative Approach

Part of the book series: Journal of Neural Transmission. Supplementa ((NEURALTRANS,volume 72))

Abstract

In Parkinson’s and other neurodegenerative diseases, a therapeutic strategy has been proposed to halt progressive cell death. Propargylamine derivatives, rasagiline and (—)deprenyl (selegiline), have been confirmed to protect neurons against cell death induced by various insults in cellular and animal models of neurodegenerative disorders. In this paper, the mechanism and the markers of the neuroprotection are reviewed. Propargylamines prevent the mitochondrial permeabilization, membrane potential decline, cytochrome c release, caspase activation and nuclear translocation of glyceraldehyde 3-phosphate dehydrogenase. At the same time, rasagiline induces anti-apoptotic pro-survival proteins, Bcl-2 and glial cell-line derived neurotrophic factor, which is mediated by activated ERK-NF-κB signal pathway. DNA array studies indicate that rasagiline increases the expression of the genes coding mitochondrial energy synthesis, inhibitors of apoptosis, transcription factors, kinases and ubiquitin-proteasome system, sequentially in a time-dependent way. Products of cell survival-related gene induced by propargylamines may be applied as markers of neuroprotection in clinical samples.

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Authors and Affiliations

  1. Department of Neurosciences, Gifu International Institute of Biotechnology, 1-1 Nakafudogaoka, Kakamigahara, Gifu, 504-0838, Japan

    M. Naoi

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

    M. Naoi, H. Yi, Y. Akao & Y. Yamaoka

  3. Department of Geriatric Medicine, National Institute for Geriatrics and Gerontology, Obu, Aichi, Japan

    W. Maruyama & M. Shamoto-Nagai

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  1. M. Naoi
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  2. W. Maruyama
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  3. H. Yi
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  4. Y. Akao
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  5. Y. Yamaoka
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  6. M. Shamoto-Nagai
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Editors and Affiliations

  1. Klinik und Poliklinik für Kinder- und Jugendpsychiatrie und Psychotherapie, Würzburg, Germany

    M. Gerlach

  2. Klinik und Poliklinik für Psychiatrie und Psychotherapie, Würzburg, Germany

    Jürgen Deckert

  3. Prince of Wales Medical Research Institute, Sydney, Australia

    K. Double

  4. Institut für Virologie und Immunobiologie, Würzburg, Germany

    E. Koutsilieri

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Naoi, M., Maruyama, W., Yi, H., Akao, Y., Yamaoka, Y., Shamoto-Nagai, M. (2007). Neuroprotection by propargylamines in Parkinson’s disease: intracellular mechanism underlying the anti-apoptotic function and search for clinical markers. In: Gerlach, M., Deckert, J., Double, K., Koutsilieri, E. (eds) Neuropsychiatric Disorders An Integrative Approach. Journal of Neural Transmission. Supplementa, vol 72. Springer, Vienna. https://doi.org/10.1007/978-3-211-73574-9_15

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  • DOI: https://doi.org/10.1007/978-3-211-73574-9_15

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