ArticleExperimental neurology2015
Overexpression of GRK6 rescues L-DOPA-induced signaling abnormalities in the dopamine-depleted striatum of hemiparkinsonian rats.
Article in Experimental neurology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Bioconversion of L-phenylalanine to L-dopaquinone by Aspergillus oryzae: a scalable model for neurological precursor synthesis.World journal of microbiology & biotechnology · 2026Article
- Modest improvement of metabolic and behavioral deficits with long-term ambroxol treatment in a Pink1Acta pharmacologica Sinica · 2026Article
- Comparative Phosphoproteomic Profiling and Network-based Interactome Analysis of GRK5 and GRK6.Cell biochemistry and biophysics · 2026Article
- S-Nitrosylation of GPCR Regulatory Machinery as a Mechanism to Bias Signaling.Handbook of experimental pharmacology · 2026Review
- Maximizing dopa-oxidase activity in Aspergillus oryzae mycelia: insights into production optimization and potential biomedical applications.International microbiology : the official journal of the Spanish Society for Microbiology · 2025Article
- Arrestin-3-assisted activation of JNK3 mediates dopaminergic behavioral sensitization.Cell reports. Medicine · 2024Article
- G protein-coupled receptor kinases are associated with Alzheimer's disease pathology.Neuropathology and applied neurobiology · 2021Article
- Current Knowledge on the Background, Pathophysiology and Treatment of Levodopa-Induced Dyskinesia-Literature Review.Journal of clinical medicine · 2021Review
- Review
- Dopamine D1 receptor signalling in dyskinetic Parkinsonian rats revealed by fiber photometry using FRET-based biosensors.Scientific reports · 2020Article
- Signal transduction in L-DOPA-induced dyskinesia: from receptor sensitization to abnormal gene expression.Journal of neural transmission (Vienna, Austria : 1996) · 2018Review
- The lentiviral-mediated Nurr1 genetic engineering mesenchymal stem cells protect dopaminergic neurons in a rat model of Parkinson's disease.American journal of translational research · 2018Article
- G Protein-Coupled Receptor Kinases in the Inflammatory Response and Signaling.Advances in immunology · 2017Review
- Current Experimental Studies of Gene Therapy in Parkinson's Disease.Frontiers in aging neuroscience · 2017Review
- G protein-coupled receptor kinases as regulators of dopamine receptor functions.Pharmacological research · 2016Review
- GRK3 suppresses L-DOPA-induced dyskinesia in the rat model of Parkinson's disease via its RGS homology domain.Scientific reports · 2015Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
l-DOPA therapy in Parkinson's disease often results in side effects such as l-DOPA-induced dyskinesia (LID). Our previous studies demonstrated that defective desensitization of dopamine receptors caused by decreased expression of G protein-coupled receptor kinases (GRKs) plays a role. Overexpression of GRK6, the isoform regulating dopamine receptors, in parkinsonian rats and monkeys alleviated LID and reduced LID-associated changes in gene expression. Here we show that 2-fold lentivirus-mediated overexpression of GRK6 in the dopamine-depleted striatum in rats unilaterally lesioned with 6-hydroxydopamine ameliorated supersensitive ERK response to l-DOPA challenge caused by loss of dopamine. A somewhat stronger effect of GRK6 was observed in drug-naïve than in chronically l-DOPA-treated animals. GRK6 reduced the responsiveness of p38 MAP kinase to l-DOPA challenge rendered supersensitive by dopamine depletion. The JNK MAP kinase was unaffected by loss of dopamine, chronic or acute l-DOPA, or GRK6. Overexpressed GRK6 suppressed enhanced activity of Akt in the lesioned striatum by reducing elevated phosphorylation at its major activating residue Thr(308). Finally, GRK6 reduced accumulation of ΔFosB in the lesioned striatum, the effect that paralleled a decrease in locomotor sensitization to l-DOPA in GRK6-expressing rats. The results suggest that elevated GRK6 facilitate desensitization of DA receptors, thereby normalizing of the activity of multiple signaling pathways implicated in LID. Thus, improving the regulation of dopamine receptor function via the desensitization mechanism could be an effective way of managing LID.
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