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New horizons in molecular mechanisms underlying Parkinson’s disease and in our understanding of the neuroprotective effects of selegiline

  • Conference paper
Deprenyl — Past and Future

Part of the book series: Journal of Neural Transmission ((NEURAL SUPPL,volume 48))

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Summary

There have been many claims that the selective monoamine oxidase type B (MAO-B) inhibitor selegiline may have distinct properties in slowing the progression of Parkinson’s disease (PD). Degeneration of nigrostriatal dopaminergic neurons is the primary histopathological feature of PD. Although many different hypotheses have been advanced, the cause of chronic nigral cell death and the underlying mechanisms remain elusive as yet. Therefore, there is no clear knowledge regarding an understanding of the reported effects of selegiline on the progression of PD. However, there is a considerable body of indirect evidence that oxidative stress may playa role in the pathogenesis of this illness. Oxidative stress refers to cytotoxic consequences of hydrogen peroxide and oxygen-derived free radicals such as the hydroxyl radical (OH), the superoxide anion (O2), and nitric oxide (NO), which are generated as byproducts of normal and aberrant metabolic processes that utilize molecular oxygen. On the other hand, an increasing body of experimental data has implicated excitotoxicity as a mechanism of cell death in both acute and chronic neurological diseases. One of the receptor which is particularly involved in the toxic effects of excitatory amino acids is the NMDA (N-methyl-D-aspartate) receptor. Excessive stimulation of this type of receptor by glutamic acid or NMDA agonists leads to a massive influx of calcium ions into the neuron followed by activation of a variety of calcium-dependent enzymes, impaired mitochondrial function, and the generation of free radicals.

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Authors and Affiliations

  1. Neurologische Klinik, Ruhr-Universität Bochum, Germany

    PD Dr. M. M. Gerlach

  2. Klinische Neurochemie, Universitäts-Nervenklinik, D-97080, Würzburg, Germany

    PD Dr. M. M. Gerlach & P. Riederer

  3. Abteilung Biochemie, Ludwig-Boltzmann-Institut für Hämatologie, Vienna, Austria

    H. Desser

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

    M. B. H. Youdim

Authors
  1. PD Dr. M. M. Gerlach
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  2. H. Desser
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  3. M. B. H. Youdim
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  4. P. Riederer
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Editor information

Editors and Affiliations

  1. Neurological Clinic, St. Josef Hospital, Bochum, Germany

    W. Kuhn , P. Kraus  & H. Przuntek ,  & 

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© 1996 Springer-Verlag/Wien

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Gerlach, M., Desser, H., Youdim, M.B.H., Riederer, P. (1996). New horizons in molecular mechanisms underlying Parkinson’s disease and in our understanding of the neuroprotective effects of selegiline. In: Kuhn, W., Kraus, P., Przuntek, H. (eds) Deprenyl — Past and Future. Journal of Neural Transmission, vol 48. Springer, Vienna. https://doi.org/10.1007/978-3-7091-7494-4_2

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  • DOI: https://doi.org/10.1007/978-3-7091-7494-4_2

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  • Print ISBN: 978-3-211-82891-5

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