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Mitochondrion- and Endoplasmic Reticulum-Induced SK Channel Dysregulation as a Potential Origin of the Selective Neurodegeneration in Parkinson’s Disease

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Systems Biology of Parkinson's Disease

Abstract

Mitochondrial dysfunction and metabolic issues are known to have strong implications in the pathogenesis of Parkinson’s disease (PD). But it is also known that the neuronal loss leading to PD symptoms is selective for particular areas of the brain (see Chap. 1). In particular, the characteristic motor symptoms of PD are mainly due to abnormal neuronal activity in the basal ganglia, through the degeneration of substantia nigra pars compacta (SNc), but not ventral tegmental area (VTA), dopaminergic (DA) neurons. How a metabolic dysfunction triggers such a selective loss is considered from a range of perspectives in several contributions to this volume. The aim of this chapter is to investigate the potential role of small conductance calcium-activated potassium (SK) channels in this selective degeneration.

Based on a recently proposed model and experimental data, we underline the fundamental role of SK channels in regulating the excitability of SNc DA neurons. The fact that SK channels do not play this regulating role in VTA DA neurons suggests the hypothesis that one reason for the preferential vulnerability of SNc DA neurons in Parkinson’s disease is that SK channels, which have a profound influence on their firing physiologically, are dysregulated by a dysfunction of mitochondria and/or endoplasmic reticulum.

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Acknowledgments

This work is supported by grant 9.4560.03 from the F.R.S.-FNRS (V.S.) and by two grants from the Belgian Science Policy (IAP6/31 (V.S.) and IAP6/4 (R.S.)).

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Authors and Affiliations

  1. Laboratory of Neurophysiology, GIGA Neurosciences, Université de Liège, Avenue de l’Hôpital 1, Bâtiment B36, 1er étage, Liège (Sart Tilman), B-4000, Belgium

    Guillaume Drion & Vincent Seutin

  2. Department of Electrical Engineering and Computer Sciences, University of Liège, Liège, Belgium

    Guillaume Drion & Rodolphe Sepulchre

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  1. Guillaume Drion
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  2. Vincent Seutin
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  3. Rodolphe Sepulchre
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Correspondence to Guillaume Drion .

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  1. , Hamilton Institute, National University of Ireland, Maynooth, Maynooth, Kildare, Ireland

    Peter Wellstead

  2. Ecole Polytechnique de Montreal, C.P. 6079, Succ. Centre-ville, Montreal, H3C 3A7, Québec, Canada

    Mathieu Cloutier

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Drion, G., Seutin, V., Sepulchre, R. (2012). Mitochondrion- and Endoplasmic Reticulum-Induced SK Channel Dysregulation as a Potential Origin of the Selective Neurodegeneration in Parkinson’s Disease. In: Wellstead, P., Cloutier, M. (eds) Systems Biology of Parkinson's Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3411-5_4

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