ParkinsonFranceV1, Ncbi, Curation, bibRecord, 001694

Targeting β-arrestin2 in the treatment of l-DOPA–induced dyskinesia in Parkinson’s disease

Identifieur interne : 001694 ( Ncbi/Curation ); précédent : 001693; suivant : 001695

Targeting β-arrestin2 in the treatment of l-DOPA–induced dyskinesia in Parkinson’s disease

Auteurs : Nikhil M. Urs ; Simone Bido [France] ; Sean M. Peterson ; Tanya L. Daigle ; Caroline E. Bass ; Raul R. Gainetdinov [Russie] ; Erwan Bezard [France] ; Marc G. Caron

Source :

Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2015.

RBID : PMC:4434696

English descriptors

KwdEn :
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (chemistry), Animals, Arrestins (genetics), Arrestins (metabolism), Behavior, Animal, Disease Models, Animal, Dopamine (metabolism), Dyskinesia, Drug-Induced (metabolism), Dyskinesias (metabolism), Gene Deletion, Levodopa (chemistry), Macaca, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Neurons (metabolism), Oxidopamine (chemistry), Parkinson Disease (drug therapy), Parkinson Disease (metabolism), Rats, Rats, Sprague-Dawley, Signal Transduction, Up-Regulation, beta-Arrestins.
MESH :
- chemical , chemistry : 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Levodopa, Oxidopamine.
- chemical , genetics : Arrestins.
- chemical , metabolism : Arrestins, Dopamine.
- drug therapy : Parkinson Disease.
- metabolism : Dyskinesia, Drug-Induced, Dyskinesias, Neurons, Parkinson Disease.
- Animals, Behavior, Animal, Disease Models, Animal, Gene Deletion, Macaca, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Rats, Rats, Sprague-Dawley, Signal Transduction, Up-Regulation, beta-Arrestins.

Abstract

Significance

β-Arrestins are unique proteins that have multiple cellular functions such as G protein-coupled receptor signal desensitization, protein trafficking and signaling molecule scaffolding. Treatment of Parkinson’s disease (PD) motor symptoms by l-3,4-dihydroxyphenylalanine (l-DOPA) has been hampered by abnormal involuntary movements or dyskinetic side effects. The cause of these dyskinesias has been attributed to receptor supersensitivity and uncontrolled neuronal excitability. Here we demonstrate in multiple preclinical models of l-DOPA–induced dyskinesias and PD that expression levels of β-arrestin2 can alter manifestation of these dyskinesias by reducing receptor supersensitivity while maintaining the therapeutic effect of l-DOPA. Thus novel drugs that increase β-arrestin–dependent function at dopamine receptors may be useful in ameliorating PD motor symptoms without inducing dyskinesias.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4434696

DOI: 10.1073/pnas.1502740112
PubMed: 25918399
PubMed Central: 4434696

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Le document en format XML

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<term>Arrestins (genetics)</term>
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<term>Behavior, Animal</term>
<term>Disease Models, Animal</term>
<term>Dopamine (metabolism)</term>
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<front><div type="abstract" xml:lang="en"><title>Significance</title>
<p>β-Arrestins are unique proteins that have multiple cellular functions such as G protein-coupled receptor signal desensitization, protein trafficking and signaling molecule scaffolding. Treatment of Parkinson’s disease (PD) motor symptoms by <sc>l</sc>
-3,4-dihydroxyphenylalanine (<sc>l</sc>
-DOPA) has been hampered by abnormal involuntary movements or dyskinetic side effects. The cause of these dyskinesias has been attributed to receptor supersensitivity and uncontrolled neuronal excitability. Here we demonstrate in multiple preclinical models of <sc>l</sc>
-DOPA–induced dyskinesias and PD that expression levels of β-arrestin2 can alter manifestation of these dyskinesias by reducing receptor supersensitivity while maintaining the therapeutic effect of <sc>l</sc>
-DOPA. Thus novel drugs that increase β-arrestin–dependent function at dopamine receptors may be useful in ameliorating PD motor symptoms without inducing dyskinesias.</p>
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	La maladie de Parkinson en France (serveur d'exploration)
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La maladie de Parkinson en France (serveur d'exploration)

Targeting β-arrestin2 in the treatment of l-DOPA–induced dyskinesia in Parkinson’s disease

Targeting β-arrestin2 in the treatment of l-DOPA–induced dyskinesia in Parkinson’s disease

Source :

English descriptors

Abstract

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