RGD Reference Report - Lentiviral overexpression of GRK6 alleviates L-dopa-induced dyskinesia in experimental Parkinson's disease. - Rat Genome Database

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Lentiviral overexpression of GRK6 alleviates L-dopa-induced dyskinesia in experimental Parkinson's disease.

Authors: Ahmed, MR  Berthet, A  Bychkov, E  Porras, G  Li, Q  Bioulac, BH  Carl, YT  Bloch, B  Kook, S  Aubert, I  Dovero, S  Doudnikoff, E  Gurevich, VV  Gurevich, EV  Bezard, E 
Citation: Ahmed MR, etal., Sci Transl Med. 2010 Apr 21;2(28):28ra28.
RGD ID: 5684919
Pubmed: PMID:20410529   (View Abstract at PubMed)
PMCID: PMC2933751   (View Article at PubMed Central)
DOI: DOI:10.1126/scitranslmed.3000664   (Journal Full-text)

Parkinson's disease is caused primarily by degeneration of brain dopaminergic neurons in the substantia nigra and the consequent deficit of dopamine in the striatum. Dopamine replacement therapy with the dopamine precursor l-dopa is the mainstay of current treatment. After several years, however, the patients develop l-dopa-induced dyskinesia, or abnormal involuntary movements, thought to be due to excessive signaling via dopamine receptors. G protein-coupled receptor kinases (GRKs) control desensitization of dopamine receptors. We found that dyskinesia is attenuated by lentivirus-mediated overexpression of GRK6 in the striatum in rodent and primate models of Parkinson's disease. Conversely, reduction of GRK6 concentration by microRNA delivered with lentiviral vector exacerbated dyskinesia in parkinsonian rats. GRK6 suppressed dyskinesia in monkeys without compromising the antiparkinsonian effects of l-dopa and even prolonged the antiparkinsonian effect of a lower dose of l-dopa. Our finding that increased availability of GRK6 ameliorates dyskinesia and increases duration of the antiparkinsonian action of l-dopa suggests a promising approach for controlling both dyskinesia and motor fluctuations in Parkinson's disease.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
GRK6HumanDrug-Induced Dyskinesia  ISOGrk6 (Rattus norvegicus)associated with Parkinson DiseaseRGD 
Grk6RatDrug-Induced Dyskinesia  IMP associated with Parkinson DiseaseRGD 
Grk6MouseDrug-Induced Dyskinesia  ISOGrk6 (Rattus norvegicus)associated with Parkinson DiseaseRGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Grk6Ratabnormal involuntary movement  IMP associated with Parkinson DiseaseRGD 
Grk6Ratabnormal locomotor behavior  IMP associated with Parkinson DiseaseRGD 
Objects Annotated

Genes (Rattus norvegicus)
Grk6  (G protein-coupled receptor kinase 6)

Genes (Mus musculus)
Grk6  (G protein-coupled receptor kinase 6)

Genes (Homo sapiens)
GRK6  (G protein-coupled receptor kinase 6)


Additional Information