The role of GRK6 in animal models of Parkinson's disease and L-DOPA treatment.
Data(s) |
2012
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Identificador |
http://www.ncbi.nlm.nih.gov/pubmed/22393477 Sci Rep, 2012, 2 pp. 301 - ? http://hdl.handle.net/10161/10773 2045-2322 |
Relação |
Sci Rep 10.1038/srep00301 |
Tipo |
Journal Article |
Cobertura |
England |
Resumo |
G protein-coupled Receptor Kinase 6 (GRK6) belongs to a family of kinases that phosphorylate GPCRs. GRK6 levels were found to be altered in Parkinson's Disease (PD) and D(2) dopamine receptors are supersensitive in mice lacking GRK6 (GRK6-KO mice). To understand how GRK6 modulates the behavioral manifestations of dopamine deficiency and responses to L-DOPA, we used three approaches to model PD in GRK6-KO mice: 1) the cataleptic response to haloperidol; 2) introducing GRK6 mutation to an acute model of absolute dopamine deficiency, DDD mice; 3) hemiparkinsonian 6-OHDA model. Furthermore, dopamine-related striatal signaling was analyzed by assessing the phosphorylation of AKT/GSK3β and ERK1/2. GRK6 deficiency reduced cataleptic behavior, potentiated the acute effect of L-DOPA in DDD mice, reduced rotational behavior in hemi-parkinsonian mice, and reduced abnormal involuntary movements induced by chronic L-DOPA. These data indicate that approaches to regulate GRK6 activity could be useful in modulating both therapeutic and side-effects of L-DOPA. |
Formato |
301 - ? |
Idioma(s) |
ENG |
Palavras-Chave | #Animals #Cyclic AMP #Disease Models, Animal #Extracellular Signal-Regulated MAP Kinases #G-Protein-Coupled Receptor Kinases #Glycogen Synthase Kinase 3 #Levodopa #Locomotion #Mice #Mice, Inbred C57BL #Mice, Knockout #Mutation #Parkinson Disease #Proto-Oncogene Proteins c-akt #Signal Transduction |