The role of GRK6 in animal models of Parkinson's disease and L-DOPA treatment.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Managò, F; Espinoza, S; Salahpour, A; Sotnikova, TD; Caron, MG; Premont, RT; Gainetdinov, RR

Published Date

  • 2012

Published In

Volume / Issue

  • 2 /

Start / End Page

  • 301 -

PubMed ID

  • 22393477

Pubmed Central ID

  • 22393477

Electronic International Standard Serial Number (EISSN)

  • 2045-2322

Digital Object Identifier (DOI)

  • 10.1038/srep00301

Language

  • eng

Conference Location

  • England