Molecular mechanisms underlying levodopa‐induced dyskinesia
Identifieur interne : 000332 ( Istex/Corpus ); précédent : 000331; suivant : 000333Molecular mechanisms underlying levodopa‐induced dyskinesia
Auteurs : Paolo Calabresi ; Massimiliano Di Filippo ; Veronica Ghiglieri ; Barbara PicconiSource :
- Movement Disorders [ 0885-3185 ] ; 2008.
English descriptors
- KwdEn :
Abstract
Although levodopa remains the most effective drug for the symptomatic treatment of Parkinson's disease, chronic therapy with this pharmacological compound initiates a complex cascade of cellular and molecular downstream effects resulting in the development of abnormal involuntary movements. The precise mechanisms underlying the development of levodopa induced dyskinesia, however, are far from being completely elucidated. In the present review, we will describe changes in long‐term synaptic excitability following dopamine (DA) denervation and long‐term levodopa treatment leading to abnormal involuntary movements. In particular, we will address the role of both DA D1 receptors and NMDA glutamate receptors in the induction and maintenance of dyskinesia and abnormal synaptic plasticity. We will also describe the possible interaction between these two receptors in the pathophysiology of dyskinesia taking the advantage of the existing knowledge concerning the mechanisms underlying drug abuse. This latter pathophysiological condition, in fact, seems to share several biochemical transduction pathways with those implicated in levodopa‐induced dyskinesia. Finally, we will briefly discuss the possible implication of A2A adenosine receptors in long‐term motor complications of levodopa therapy and focus on the interaction between A2A and D2 receptors. Future studies are required to understand how the interaction between these various biochemical steps converge to produce a long‐term change in neuronal excitability within the basal ganglia leading to abnormal involuntary movements following levodopa treatment in the DA‐denervated state. © 2008 Movement Disorder Society
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DOI: 10.1002/mds.22019
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ISTEX:CECD3BD602E3EF08DE4FC10AFFFC472FFD82FDBALe document en format XML
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The precise mechanisms underlying the development of levodopa induced dyskinesia, however, are far from being completely elucidated. In the present review, we will describe changes in long‐term synaptic excitability following dopamine (DA) denervation and long‐term levodopa treatment leading to abnormal involuntary movements. In particular, we will address the role of both DA D1 receptors and NMDA glutamate receptors in the induction and maintenance of dyskinesia and abnormal synaptic plasticity. We will also describe the possible interaction between these two receptors in the pathophysiology of dyskinesia taking the advantage of the existing knowledge concerning the mechanisms underlying drug abuse. This latter pathophysiological condition, in fact, seems to share several biochemical transduction pathways with those implicated in levodopa‐induced dyskinesia. Finally, we will briefly discuss the possible implication of A2A adenosine receptors in long‐term motor complications of levodopa therapy and focus on the interaction between A2A and D2 receptors. Future studies are required to understand how the interaction between these various biochemical steps converge to produce a long‐term change in neuronal excitability within the basal ganglia leading to abnormal involuntary movements following levodopa treatment in the DA‐denervated state. © 2008 Movement Disorder Society</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Paolo Calabresi MD</name><affiliations><json:string>Clinica Neurologica, Università degli Studi di Perugia, Ospedale S. 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Maria della Misericordia, Perugia, Italy</json:string><json:string>IRCCS Fondazione Santa Lucia, Rome, Italy</json:string></affiliations></json:item><json:item><name>Veronica Ghiglieri PhD</name><affiliations><json:string>IRCCS Fondazione Santa Lucia, Rome, Italy</json:string></affiliations></json:item><json:item><name>Barbara Picconi PhD</name><affiliations><json:string>IRCCS Fondazione Santa Lucia, Rome, Italy</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Parkinson's disease</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>dyskinesia</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>L‐dopa</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>synaptic plasticity</value></json:item></subject><language><json:string>eng</json:string></language><abstract>Although levodopa remains the most effective drug for the symptomatic treatment of Parkinson's disease, chronic therapy with this pharmacological compound initiates a complex cascade of cellular and molecular downstream effects resulting in the development of abnormal involuntary movements. 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Finally, we will briefly discuss the possible implication of A2A adenosine receptors in long‐term motor complications of levodopa therapy and focus on the interaction between A2A and D2 receptors. 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The precise mechanisms underlying the development of levodopa induced dyskinesia, however, are far from being completely elucidated. In the present review, we will describe changes in long‐term synaptic excitability following dopamine (DA) denervation and long‐term levodopa treatment leading to abnormal involuntary movements. In particular, we will address the role of both DA D1 receptors and NMDA glutamate receptors in the induction and maintenance of dyskinesia and abnormal synaptic plasticity. We will also describe the possible interaction between these two receptors in the pathophysiology of dyskinesia taking the advantage of the existing knowledge concerning the mechanisms underlying drug abuse. This latter pathophysiological condition, in fact, seems to share several biochemical transduction pathways with those implicated in levodopa‐induced dyskinesia. Finally, we will briefly discuss the possible implication of A2A adenosine receptors in long‐term motor complications of levodopa therapy and focus on the interaction between A2A and D2 receptors. Future studies are required to understand how the interaction between these various biochemical steps converge to produce a long‐term change in neuronal excitability within the basal ganglia leading to abnormal involuntary movements following levodopa treatment in the DA‐denervated state. © 2008 Movement Disorder Society</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>Parkinson's disease</term></item><item><term>dyskinesia</term></item><item><term>L‐dopa</term></item><item><term>synaptic plasticity</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head>Article category</head><item><term>Research Article</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2007-12-31">Received</change><change when="2008-02-12">Registration</change><change when="2008">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/CECD3BD602E3EF08DE4FC10AFFFC472FFD82FDBA/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>Wiley Subscription Services, Inc., A Wiley Company</publisherName><publisherLoc>Hoboken</publisherLoc></publisherInfo><doi registered="yes">10.1002/(ISSN)1531-8257</doi><issn type="print">0885-3185</issn><issn type="electronic">1531-8257</issn><idGroup><id type="product" value="MDS"></id></idGroup><titleGroup><title type="main" xml:lang="en" sort="MOVEMENT DISORDERS">Movement Disorders</title><title type="subtitle">Official Journal of the Movement Disorder Society</title><title type="short">Mov. 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Maria della Misericordia, Perugia, Italy</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="IT" type="organization"><unparsedAffiliation>IRCCS Fondazione Santa Lucia, Rome, Italy</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1">Parkinson's disease</keyword><keyword xml:id="kwd2">dyskinesia</keyword><keyword xml:id="kwd3"><sc>L</sc>‐dopa</keyword><keyword xml:id="kwd4">synaptic plasticity</keyword></keywordGroup><fundingInfo><fundingAgency>Fondo per gli Investimenti della Ricerca di Base 2003</fundingAgency><fundingNumber>FIRB2003</fundingNumber></fundingInfo><fundingInfo><fundingAgency>Ricerca Scientifica di Rilevante Interesse Nazionale 2005</fundingAgency><fundingNumber>PRIN2005</fundingNumber></fundingInfo><fundingInfo><fundingAgency>Progetti Finalizzati e Strategici Ministero della Salute 2004</fundingAgency></fundingInfo><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>Although levodopa remains the most effective drug for the symptomatic treatment of Parkinson's disease, chronic therapy with this pharmacological compound initiates a complex cascade of cellular and molecular downstream effects resulting in the development of abnormal involuntary movements. The precise mechanisms underlying the development of levodopa induced dyskinesia, however, are far from being completely elucidated. In the present review, we will describe changes in long‐term synaptic excitability following dopamine (DA) denervation and long‐term levodopa treatment leading to abnormal involuntary movements. In particular, we will address the role of both DA D1 receptors and NMDA glutamate receptors in the induction and maintenance of dyskinesia and abnormal synaptic plasticity. We will also describe the possible interaction between these two receptors in the pathophysiology of dyskinesia taking the advantage of the existing knowledge concerning the mechanisms underlying drug abuse. This latter pathophysiological condition, in fact, seems to share several biochemical transduction pathways with those implicated in levodopa‐induced dyskinesia. Finally, we will briefly discuss the possible implication of A2A adenosine receptors in long‐term motor complications of levodopa therapy and focus on the interaction between A2A and D2 receptors. Future studies are required to understand how the interaction between these various biochemical steps converge to produce a long‐term change in neuronal excitability within the basal ganglia leading to abnormal involuntary movements following levodopa treatment in the DA‐denervated state. © 2008 Movement Disorder Society</p></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="fn1"><p>Potential conflict of interest: Nothing to report.</p></note></noteGroup></header></component></istex:document></istex:metadataXml><!--Version 0.6 générée le 3-12-2015--><mods version="3.6"><titleInfo lang="en"><title>Molecular mechanisms underlying levodopa‐induced dyskinesia</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>Mechanisms Underlying Levodopa‐Induced Dyskinesia</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Molecular mechanisms underlying levodopa‐induced dyskinesia</title></titleInfo><name type="personal"><namePart type="given">Paolo</namePart><namePart type="family">Calabresi</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Clinica Neurologica, Università degli Studi di Perugia, Ospedale S. Maria della Misericordia, Perugia, Italy</affiliation><affiliation>IRCCS Fondazione Santa Lucia, Rome, Italy</affiliation><description>Correspondence: Clinica Neurologica, Università di Perugia, Ospedale S. Maria della Misericordia, Via S Andrea delle Fratte, 06156, Perugia, Italy</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Massimiliano</namePart><namePart type="family">Di Filippo</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Clinica Neurologica, Università degli Studi di Perugia, Ospedale S. Maria della Misericordia, Perugia, Italy</affiliation><affiliation>IRCCS Fondazione Santa Lucia, Rome, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Veronica</namePart><namePart type="family">Ghiglieri</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>IRCCS Fondazione Santa Lucia, Rome, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Barbara</namePart><namePart type="family">Picconi</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>IRCCS Fondazione Santa Lucia, Rome, Italy</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre authority="originalCategForm">article</genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2008</dateIssued><dateCaptured encoding="w3cdtf">2007-12-31</dateCaptured><dateValid encoding="w3cdtf">2008-02-12</dateValid><copyrightDate encoding="w3cdtf">2008</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="figures">3</extent><extent unit="references">49</extent><extent unit="words">5842</extent></physicalDescription><abstract lang="en">Although levodopa remains the most effective drug for the symptomatic treatment of Parkinson's disease, chronic therapy with this pharmacological compound initiates a complex cascade of cellular and molecular downstream effects resulting in the development of abnormal involuntary movements. The precise mechanisms underlying the development of levodopa induced dyskinesia, however, are far from being completely elucidated. In the present review, we will describe changes in long‐term synaptic excitability following dopamine (DA) denervation and long‐term levodopa treatment leading to abnormal involuntary movements. In particular, we will address the role of both DA D1 receptors and NMDA glutamate receptors in the induction and maintenance of dyskinesia and abnormal synaptic plasticity. We will also describe the possible interaction between these two receptors in the pathophysiology of dyskinesia taking the advantage of the existing knowledge concerning the mechanisms underlying drug abuse. This latter pathophysiological condition, in fact, seems to share several biochemical transduction pathways with those implicated in levodopa‐induced dyskinesia. Finally, we will briefly discuss the possible implication of A2A adenosine receptors in long‐term motor complications of levodopa therapy and focus on the interaction between A2A and D2 receptors. Future studies are required to understand how the interaction between these various biochemical steps converge to produce a long‐term change in neuronal excitability within the basal ganglia leading to abnormal involuntary movements following levodopa treatment in the DA‐denervated state. © 2008 Movement Disorder Society</abstract><note type="content">*Potential conflict of interest: Nothing to report.</note><note type="funding">Fondo per gli Investimenti della Ricerca di Base 2003 - No. FIRB2003; </note><note type="funding">Ricerca Scientifica di Rilevante Interesse Nazionale 2005 - No. PRIN2005; </note><note type="funding">Progetti Finalizzati e Strategici Ministero della Salute 2004</note><subject lang="en"><genre>Keywords</genre><topic>Parkinson's disease</topic><topic>dyskinesia</topic><topic>L‐dopa</topic><topic>synaptic plasticity</topic></subject><relatedItem type="host"><titleInfo><title>Movement Disorders</title><subTitle>Official Journal of the Movement Disorder Society</subTitle></titleInfo><titleInfo type="abbreviated"><title>Mov. Disord.</title></titleInfo><subject><genre>article category</genre><topic>Research Article</topic></subject><identifier type="ISSN">0885-3185</identifier><identifier type="eISSN">1531-8257</identifier><identifier type="DOI">10.1002/(ISSN)1531-8257</identifier><identifier type="PublisherID">MDS</identifier><part><date>2008</date><detail type="volume"><caption>vol.</caption><number>23</number></detail><detail type="issue"><caption>no.</caption><number>S3</number></detail><detail type="supplement"><caption>Suppl. no.</caption><number>S3</number></detail><extent unit="pages"><start>S570</start><end>S579</end><total>10</total></extent></part></relatedItem><identifier type="istex">CECD3BD602E3EF08DE4FC10AFFFC472FFD82FDBA</identifier><identifier type="DOI">10.1002/mds.22019</identifier><identifier type="ArticleID">MDS22019</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2008 Movement Disorder Society</accessCondition><recordInfo><recordOrigin>Wiley Subscription Services, Inc., A Wiley Company</recordOrigin><recordContentSource>WILEY</recordContentSource></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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