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Mechanism and consequences of nerve cell death in Parkinson’s disease

  • Conference paper
Diagnosis and Treatment of Parkinson’s Disease — State of the Art

Part of the book series: Journal of Neural Transmission. Supplementa ((NEURAL SUPPL,volume 56))

Summary

The etiology of Parkinson’s disease remains unknown, making it difficult to develop therapeutical approaches to stop the progression of the disease. The best known treatment to date is based on the use of L-DOPA or dopaminergic agonists. These are merely substitutive therapies and have limitations because of their side effects. Thus, the development of new therapeutical strategies will require a far better knowledge of the mechanism and the consequences of nerve cell death in Parkinson’s disease.

Parkinson’s disease is characterized by a selective vulnerability of sub-populations of dopaminergic neurons in the mesencephalon. The fact that the neurons which degenerate in Parkinson’s disease are already sensitive to oxidative stress in control subjects and the reported increased production of oxygen free radicals in Parkinson’s disease suggest that oxidative stress may be involved in the mechanism of nerve cell death. Furthermore, oxygen free radicals are also involved in an oxygen-dependent pro-apoptotic pathway stimulated by the inflammatory reaction observed in Parkinson’s disease. These data suggest that anti-oxidant or anti-inflammatory treatments may slow down the progression of the disease.

On the other hand, new substitutive therapies may be developed by trying to restore the activity of the neurons located downstream from the nigrostriatal pathway. Indeed, the nigrostriatal denervation induces a hyper- activity of the output structures of the basal ganglia (internal segment of the globus pallidus and substantia nigra pars reticulata), as demonstrated in various animal models of the disease. These changes in the activity of the output structures of the basal ganglia seem to be directly induced by the hyperactivity of the glutamatergic afferent fibers from the subthalamic nucleus. The fact that L-DOPA treatment or a reduction in the activity of the subthalamic nucleus alleviate the symptoms of the disease and restore the activity of the output structures of the basal ganglia in parkinsonism suggests that these structures play a key role in the pathophysiology of the disease and could represent a potential therapeutic target.

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Authors and Affiliations

  1. Recherche CNRS, Hôpital de la Sâlpêtrière, 47 boulevard de l’Hôpital, F-75013, Paris Cedex 13, France

    Prof. Dr. Etienne C. Hirsch

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  1. Prof. Dr. Etienne C. Hirsch
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  1. Department of Neurology, St. Josef Hospital Ruhr University Bochum, Federal Republic of Germany

    H. Przuntek  & T. Müller  & 

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© 1999 Springer-Verlag Wien

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Hirsch, E.C. (1999). Mechanism and consequences of nerve cell death in Parkinson’s disease. In: Przuntek, H., Müller, T. (eds) Diagnosis and Treatment of Parkinson’s Disease — State of the Art. Journal of Neural Transmission. Supplementa, vol 56. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6360-3_7

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  • DOI: https://doi.org/10.1007/978-3-7091-6360-3_7

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-211-83275-2

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