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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
28
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pubmed:dateCreated |
2010-4-22
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pubmed:abstractText |
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.
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pubmed:grant |
http://linkedlifedata.com/resource/pubmed/grant/EY011500,
http://linkedlifedata.com/resource/pubmed/grant/GM077561,
http://linkedlifedata.com/resource/pubmed/grant/GM081756,
http://linkedlifedata.com/resource/pubmed/grant/NS065868,
http://linkedlifedata.com/resource/pubmed/grant/NS45117,
http://linkedlifedata.com/resource/pubmed/grant/R01 EY011500-10,
http://linkedlifedata.com/resource/pubmed/grant/R01 GM077561-01A1,
http://linkedlifedata.com/resource/pubmed/grant/R01 GM077561-01A1S1,
http://linkedlifedata.com/resource/pubmed/grant/R01 GM077561-02,
http://linkedlifedata.com/resource/pubmed/grant/R01 GM077561-03,
http://linkedlifedata.com/resource/pubmed/grant/R01 GM081756-01A1,
http://linkedlifedata.com/resource/pubmed/grant/R01 GM081756-02,
http://linkedlifedata.com/resource/pubmed/grant/R01 GM081756-02S1,
http://linkedlifedata.com/resource/pubmed/grant/R01 GM081756-03,
http://linkedlifedata.com/resource/pubmed/grant/R01 NS045117-01A1,
http://linkedlifedata.com/resource/pubmed/grant/R01 NS045117-02,
http://linkedlifedata.com/resource/pubmed/grant/R01 NS045117-03,
http://linkedlifedata.com/resource/pubmed/grant/R01 NS045117-04,
http://linkedlifedata.com/resource/pubmed/grant/R01 NS045117-05,
http://linkedlifedata.com/resource/pubmed/grant/R01 NS065868-01
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/1-Methyl-4-phenyl-1,2,3,6-tetrahydro...,
http://linkedlifedata.com/resource/pubmed/chemical/Antiparkinson Agents,
http://linkedlifedata.com/resource/pubmed/chemical/G-Protein-Coupled Receptor Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/G-protein-coupled receptor kinase 6,
http://linkedlifedata.com/resource/pubmed/chemical/Levodopa,
http://linkedlifedata.com/resource/pubmed/chemical/Oxidopamine,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Dopamine D1,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Dopamine D2
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1946-6242
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pubmed:author |
pubmed-author:AhmedMohamed RMR,
pubmed-author:AubertIncarnationI,
pubmed-author:BerthetAmandineA,
pubmed-author:BezardErwanE,
pubmed-author:BioulacBernard HBH,
pubmed-author:BlochBertrandB,
pubmed-author:BychkovEvgenyE,
pubmed-author:CarlYonatan TYT,
pubmed-author:DoudnikoffEvelyneE,
pubmed-author:DoveroSandraS,
pubmed-author:GurevichEugenia VEV,
pubmed-author:GurevichVsevolod VVV,
pubmed-author:KookSeunghyiS,
pubmed-author:OcaFF,
pubmed-author:PorrasGregoryG
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pubmed:issnType |
Electronic
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pubmed:day |
21
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pubmed:volume |
2
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
28ra28
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pubmed:dateRevised |
2011-9-26
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pubmed:meshHeading |
pubmed-meshheading:20410529-1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine,
pubmed-meshheading:20410529-Animals,
pubmed-meshheading:20410529-Antiparkinson Agents,
pubmed-meshheading:20410529-Behavior, Animal,
pubmed-meshheading:20410529-Dose-Response Relationship, Drug,
pubmed-meshheading:20410529-Dyskinesias,
pubmed-meshheading:20410529-Endocytosis,
pubmed-meshheading:20410529-G-Protein-Coupled Receptor Kinases,
pubmed-meshheading:20410529-Gene Knockdown Techniques,
pubmed-meshheading:20410529-Gene Therapy,
pubmed-meshheading:20410529-Humans,
pubmed-meshheading:20410529-Lentivirus,
pubmed-meshheading:20410529-Levodopa,
pubmed-meshheading:20410529-Macaca,
pubmed-meshheading:20410529-Oxidopamine,
pubmed-meshheading:20410529-Parkinsonian Disorders,
pubmed-meshheading:20410529-Rats,
pubmed-meshheading:20410529-Rats, Sprague-Dawley,
pubmed-meshheading:20410529-Receptors, Dopamine D1,
pubmed-meshheading:20410529-Receptors, Dopamine D2,
pubmed-meshheading:20410529-Rotation,
pubmed-meshheading:20410529-Signal Transduction
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pubmed:year |
2010
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pubmed:articleTitle |
Lentiviral overexpression of GRK6 alleviates L-dopa-induced dyskinesia in experimental Parkinson's disease.
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pubmed:affiliation |
Department of Pharmacology, Vanderbilt University, 2200 Pierce Avenue, PRB422, Nashville, TN 37232, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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