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Mitochondrion- and endoplasmic reticulum-induced SK channel dysregulation as a potential origin of the selective neurodegeneration in Parkinson’s disease
Drion, Guillaume; Sepulchre, Rodolphe; Seutin, Vincent
2012In Wellstead, Peter; Cloutier, Mathieu (Eds.) The Systems Biology of Parkinson's Disease
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Abstract :
[en] 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. 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.
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
Drion, Guillaume ;  Université de Liège - ULiège > R&D Direction : Chercheurs ULiège en mobilité
Sepulchre, Rodolphe ;  Université de Liège - ULiège > Dép. d'électric., électron. et informat. (Inst.Montefiore) > Systèmes et modélisation
Seutin, Vincent ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Pharmacologie
Language :
English
Title :
Mitochondrion- and endoplasmic reticulum-induced SK channel dysregulation as a potential origin of the selective neurodegeneration in Parkinson’s disease
Publication date :
2012
Main work title :
The Systems Biology of Parkinson's Disease
Editor :
Wellstead, Peter
Cloutier, Mathieu
Publisher :
Springer
Peer reviewed :
Peer reviewed
Available on ORBi :
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