PSD-95 expression controls l-DOPA dyskinesia through dopamine D1 receptor trafficking
Identifieur interne : 001090 ( Main/Exploration ); précédent : 001089; suivant : 001091PSD-95 expression controls l-DOPA dyskinesia through dopamine D1 receptor trafficking
Auteurs : Gregory Porras [France] ; Amandine Berthet [France] ; Benjamin Dehay [France] ; Qin Li [République populaire de Chine] ; Laurent Ladepeche [France] ; Elisabeth Normand [France] ; Sandra Dovero [France] ; Audrey Martinez [France] ; Evelyne Doudnikoff [France] ; Marie-Laure Martin-Négrier [France] ; Qin Chuan [République populaire de Chine] ; Bertrand Bloch [France] ; Daniel Choquet [France] ; Eric Boué-Grabot [France] ; Laurent Groc [France] ; Erwan Bezard [France, République populaire de Chine]Source :
- The Journal of Clinical Investigation [ 0021-9738 ] ; 2012.
English descriptors
- KwdEn :
- Animals, Corpus Striatum (metabolism), Corpus Striatum (pathology), Dyskinesia, Drug-Induced (genetics), Dyskinesia, Drug-Induced (metabolism), Dyskinesia, Drug-Induced (pathology), HEK293 Cells, Humans, Intracellular Signaling Peptides and Proteins (genetics), Intracellular Signaling Peptides and Proteins (metabolism), Levodopa (adverse effects), Levodopa (pharmacology), Macaca, Male, Membrane Proteins (genetics), Membrane Proteins (metabolism), Parkinson Disease (genetics), Parkinson Disease (metabolism), Parkinson Disease (pathology), Parkinson Disease (therapy), Protein Transport (drug effects), Rats, Rats, Sprague-Dawley, Receptors, Dopamine D1 (genetics), Receptors, Dopamine D1 (metabolism), Synapses (genetics), Synapses (metabolism).
- MESH :
- chemical , adverse effects : Levodopa.
- chemical , genetics : Intracellular Signaling Peptides and Proteins, Membrane Proteins, Receptors, Dopamine D1.
- drug effects : Protein Transport.
- genetics : Dyskinesia, Drug-Induced, Parkinson Disease, Synapses.
- metabolism : Corpus Striatum, Dyskinesia, Drug-Induced, Intracellular Signaling Peptides and Proteins, Membrane Proteins, Parkinson Disease, Receptors, Dopamine D1, Synapses.
- pathology : Corpus Striatum, Dyskinesia, Drug-Induced, Parkinson Disease.
- chemical , pharmacology : Levodopa.
- therapy : Parkinson Disease.
- Animals, HEK293 Cells, Humans, Macaca, Male, Rats, Rats, Sprague-Dawley.
Abstract
Url:
DOI: 10.1172/JCI59426
PubMed: 23041629
PubMed Central: 3484432
Affiliations:
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Le document en format XML
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-DOPA dyskinesia through dopamine D1 receptor trafficking
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-DOPA dyskinesia through dopamine D1 receptor trafficking
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<author><name sortKey="Martinez, Audrey" sort="Martinez, Audrey" uniqKey="Martinez A" first="Audrey" last="Martinez">Audrey Martinez</name>
<affiliation><nlm:aff wicri:cut=" and" id="JCI59426">Université de Bordeaux</nlm:aff>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="JCI59426">CNRS, Institut des Maladies Neurodégénératives, Bordeaux, France.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">France</country>
<wicri:regionArea>CNRS, Institut des Maladies Neurodégénératives, Bordeaux</wicri:regionArea>
<placeName><region type="region">Nouvelle-Aquitaine</region>
<region type="old region">Aquitaine</region>
<settlement type="city">Bordeaux</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Doudnikoff, Evelyne" sort="Doudnikoff, Evelyne" uniqKey="Doudnikoff E" first="Evelyne" last="Doudnikoff">Evelyne Doudnikoff</name>
<affiliation><nlm:aff wicri:cut=" and" id="JCI59426">Université de Bordeaux</nlm:aff>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="JCI59426">CNRS, Institut des Maladies Neurodégénératives, Bordeaux, France.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">France</country>
<wicri:regionArea>CNRS, Institut des Maladies Neurodégénératives, Bordeaux</wicri:regionArea>
<placeName><region type="region">Nouvelle-Aquitaine</region>
<region type="old region">Aquitaine</region>
<settlement type="city">Bordeaux</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Martin Negrier, Marie Laure" sort="Martin Negrier, Marie Laure" uniqKey="Martin Negrier M" first="Marie-Laure" last="Martin-Négrier">Marie-Laure Martin-Négrier</name>
<affiliation><nlm:aff wicri:cut=" and" id="JCI59426">Université de Bordeaux</nlm:aff>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="JCI59426">CNRS, Institut des Maladies Neurodégénératives, Bordeaux, France.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">France</country>
<wicri:regionArea>CNRS, Institut des Maladies Neurodégénératives, Bordeaux</wicri:regionArea>
<placeName><region type="region">Nouvelle-Aquitaine</region>
<region type="old region">Aquitaine</region>
<settlement type="city">Bordeaux</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Chuan, Qin" sort="Chuan, Qin" uniqKey="Chuan Q" first="Qin" last="Chuan">Qin Chuan</name>
<affiliation wicri:level="3"><nlm:aff id="JCI59426">Institute of Lab Animal Sciences, China Academy of Medical Sciences, Beijing, China.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country>
<wicri:regionArea>Institute of Lab Animal Sciences, China Academy of Medical Sciences, Beijing</wicri:regionArea>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bloch, Bertrand" sort="Bloch, Bertrand" uniqKey="Bloch B" first="Bertrand" last="Bloch">Bertrand Bloch</name>
<affiliation><nlm:aff wicri:cut=" and" id="JCI59426">Université de Bordeaux</nlm:aff>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="JCI59426">CNRS, Institut des Maladies Neurodégénératives, Bordeaux, France.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">France</country>
<wicri:regionArea>CNRS, Institut des Maladies Neurodégénératives, Bordeaux</wicri:regionArea>
<placeName><region type="region">Nouvelle-Aquitaine</region>
<region type="old region">Aquitaine</region>
<settlement type="city">Bordeaux</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Choquet, Daniel" sort="Choquet, Daniel" uniqKey="Choquet D" first="Daniel" last="Choquet">Daniel Choquet</name>
<affiliation><nlm:aff wicri:cut=" and" id="JCI59426">Université de Bordeaux</nlm:aff>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="JCI59426">CNRS, Institut Interdisciplinaire des Neurosciences, Bordeaux, France.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">France</country>
<wicri:regionArea>CNRS, Institut Interdisciplinaire des Neurosciences, Bordeaux</wicri:regionArea>
<placeName><region type="region">Nouvelle-Aquitaine</region>
<region type="old region">Aquitaine</region>
<settlement type="city">Bordeaux</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Boue Grabot, Eric" sort="Boue Grabot, Eric" uniqKey="Boue Grabot E" first="Eric" last="Boué-Grabot">Eric Boué-Grabot</name>
<affiliation><nlm:aff wicri:cut=" and" id="JCI59426">Université de Bordeaux</nlm:aff>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="JCI59426">CNRS, Institut des Maladies Neurodégénératives, Bordeaux, France.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">France</country>
<wicri:regionArea>CNRS, Institut des Maladies Neurodégénératives, Bordeaux</wicri:regionArea>
<placeName><region type="region">Nouvelle-Aquitaine</region>
<region type="old region">Aquitaine</region>
<settlement type="city">Bordeaux</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Groc, Laurent" sort="Groc, Laurent" uniqKey="Groc L" first="Laurent" last="Groc">Laurent Groc</name>
<affiliation><nlm:aff wicri:cut=" and" id="JCI59426">Université de Bordeaux</nlm:aff>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="JCI59426">CNRS, Institut Interdisciplinaire des Neurosciences, Bordeaux, France.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">France</country>
<wicri:regionArea>CNRS, Institut Interdisciplinaire des Neurosciences, Bordeaux</wicri:regionArea>
<placeName><region type="region">Nouvelle-Aquitaine</region>
<region type="old region">Aquitaine</region>
<settlement type="city">Bordeaux</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bezard, Erwan" sort="Bezard, Erwan" uniqKey="Bezard E" first="Erwan" last="Bezard">Erwan Bezard</name>
<affiliation><nlm:aff wicri:cut=" and" id="JCI59426">Université de Bordeaux</nlm:aff>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="JCI59426">CNRS, Institut des Maladies Neurodégénératives, Bordeaux, France.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">France</country>
<wicri:regionArea>CNRS, Institut des Maladies Neurodégénératives, Bordeaux</wicri:regionArea>
<placeName><region type="region">Nouvelle-Aquitaine</region>
<region type="old region">Aquitaine</region>
<settlement type="city">Bordeaux</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="JCI59426">Institute of Lab Animal Sciences, China Academy of Medical Sciences, Beijing, China.</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country>
<wicri:regionArea>Institute of Lab Animal Sciences, China Academy of Medical Sciences, Beijing</wicri:regionArea>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">The Journal of Clinical Investigation</title>
<idno type="ISSN">0021-9738</idno>
<idno type="eISSN">1558-8238</idno>
<imprint><date when="2012">2012</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term>
<term>Corpus Striatum (metabolism)</term>
<term>Corpus Striatum (pathology)</term>
<term>Dyskinesia, Drug-Induced (genetics)</term>
<term>Dyskinesia, Drug-Induced (metabolism)</term>
<term>Dyskinesia, Drug-Induced (pathology)</term>
<term>HEK293 Cells</term>
<term>Humans</term>
<term>Intracellular Signaling Peptides and Proteins (genetics)</term>
<term>Intracellular Signaling Peptides and Proteins (metabolism)</term>
<term>Levodopa (adverse effects)</term>
<term>Levodopa (pharmacology)</term>
<term>Macaca</term>
<term>Male</term>
<term>Membrane Proteins (genetics)</term>
<term>Membrane Proteins (metabolism)</term>
<term>Parkinson Disease (genetics)</term>
<term>Parkinson Disease (metabolism)</term>
<term>Parkinson Disease (pathology)</term>
<term>Parkinson Disease (therapy)</term>
<term>Protein Transport (drug effects)</term>
<term>Rats</term>
<term>Rats, Sprague-Dawley</term>
<term>Receptors, Dopamine D1 (genetics)</term>
<term>Receptors, Dopamine D1 (metabolism)</term>
<term>Synapses (genetics)</term>
<term>Synapses (metabolism)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Levodopa</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Intracellular Signaling Peptides and Proteins</term>
<term>Membrane Proteins</term>
<term>Receptors, Dopamine D1</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Protein Transport</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Dyskinesia, Drug-Induced</term>
<term>Parkinson Disease</term>
<term>Synapses</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Corpus Striatum</term>
<term>Dyskinesia, Drug-Induced</term>
<term>Intracellular Signaling Peptides and Proteins</term>
<term>Membrane Proteins</term>
<term>Parkinson Disease</term>
<term>Receptors, Dopamine D1</term>
<term>Synapses</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Corpus Striatum</term>
<term>Dyskinesia, Drug-Induced</term>
<term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Levodopa</term>
</keywords>
<keywords scheme="MESH" qualifier="therapy" xml:lang="en"><term>Parkinson Disease</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>HEK293 Cells</term>
<term>Humans</term>
<term>Macaca</term>
<term>Male</term>
<term>Rats</term>
<term>Rats, Sprague-Dawley</term>
</keywords>
</textClass>
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</teiHeader>
<front><div type="abstract" xml:lang="en"><p><sc>l</sc>
-DOPA–induced dyskinesia (LID), a detrimental consequence of dopamine replacement therapy for Parkinson’s disease, is associated with an alteration in dopamine D1 receptor (D1R) and glutamate receptor interactions. We hypothesized that the synaptic scaffolding protein PSD-95 plays a pivotal role in this process, as it interacts with D1R, regulates its trafficking and function, and is overexpressed in LID. Here, we demonstrate in rat and macaque models that disrupting the interaction between D1R and PSD-95 in the striatum reduces LID development and severity. Single quantum dot imaging revealed that this benefit was achieved primarily by destabilizing D1R localization, via increased lateral diffusion followed by increased internalization and diminished surface expression. These findings indicate that altering D1R trafficking via synapse-associated scaffolding proteins may be useful in the treatment of dyskinesia in Parkinson’s patients.
</p>
</div>
</front>
</TEI>
<affiliations><list><country><li>France</li>
<li>République populaire de Chine</li>
</country>
<region><li>Aquitaine</li>
<li>Nouvelle-Aquitaine</li>
</region>
<settlement><li>Bordeaux</li>
<li>Pékin</li>
</settlement>
</list>
<tree><country name="France"><region name="Nouvelle-Aquitaine"><name sortKey="Porras, Gregory" sort="Porras, Gregory" uniqKey="Porras G" first="Gregory" last="Porras">Gregory Porras</name>
</region>
<name sortKey="Berthet, Amandine" sort="Berthet, Amandine" uniqKey="Berthet A" first="Amandine" last="Berthet">Amandine Berthet</name>
<name sortKey="Bezard, Erwan" sort="Bezard, Erwan" uniqKey="Bezard E" first="Erwan" last="Bezard">Erwan Bezard</name>
<name sortKey="Bloch, Bertrand" sort="Bloch, Bertrand" uniqKey="Bloch B" first="Bertrand" last="Bloch">Bertrand Bloch</name>
<name sortKey="Boue Grabot, Eric" sort="Boue Grabot, Eric" uniqKey="Boue Grabot E" first="Eric" last="Boué-Grabot">Eric Boué-Grabot</name>
<name sortKey="Choquet, Daniel" sort="Choquet, Daniel" uniqKey="Choquet D" first="Daniel" last="Choquet">Daniel Choquet</name>
<name sortKey="Dehay, Benjamin" sort="Dehay, Benjamin" uniqKey="Dehay B" first="Benjamin" last="Dehay">Benjamin Dehay</name>
<name sortKey="Doudnikoff, Evelyne" sort="Doudnikoff, Evelyne" uniqKey="Doudnikoff E" first="Evelyne" last="Doudnikoff">Evelyne Doudnikoff</name>
<name sortKey="Dovero, Sandra" sort="Dovero, Sandra" uniqKey="Dovero S" first="Sandra" last="Dovero">Sandra Dovero</name>
<name sortKey="Groc, Laurent" sort="Groc, Laurent" uniqKey="Groc L" first="Laurent" last="Groc">Laurent Groc</name>
<name sortKey="Ladepeche, Laurent" sort="Ladepeche, Laurent" uniqKey="Ladepeche L" first="Laurent" last="Ladepeche">Laurent Ladepeche</name>
<name sortKey="Martin Negrier, Marie Laure" sort="Martin Negrier, Marie Laure" uniqKey="Martin Negrier M" first="Marie-Laure" last="Martin-Négrier">Marie-Laure Martin-Négrier</name>
<name sortKey="Martinez, Audrey" sort="Martinez, Audrey" uniqKey="Martinez A" first="Audrey" last="Martinez">Audrey Martinez</name>
<name sortKey="Normand, Elisabeth" sort="Normand, Elisabeth" uniqKey="Normand E" first="Elisabeth" last="Normand">Elisabeth Normand</name>
</country>
<country name="République populaire de Chine"><noRegion><name sortKey="Li, Qin" sort="Li, Qin" uniqKey="Li Q" first="Qin" last="Li">Qin Li</name>
</noRegion>
<name sortKey="Bezard, Erwan" sort="Bezard, Erwan" uniqKey="Bezard E" first="Erwan" last="Bezard">Erwan Bezard</name>
<name sortKey="Chuan, Qin" sort="Chuan, Qin" uniqKey="Chuan Q" first="Qin" last="Chuan">Qin Chuan</name>
</country>
</tree>
</affiliations>
</record>
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