Metabotropic Glutamate Receptors for Parkinson's Disease Therapy
Identifieur interne : 000D33 ( Main/Exploration ); précédent : 000D32; suivant : 000D34Metabotropic Glutamate Receptors for Parkinson's Disease Therapy
Auteurs : Fabrizio Gasparini [Suisse] ; Thérèse Di Paolo [Canada] ; Baltazar Gomez-Mancilla [Suisse]Source :
- Parkinson's Disease [ 2090-8083 ] ; 2013.
Abstract
Excessive glutamatergic signalling within the basal ganglia is implicated in the progression of Parkinson's disease (PD) and inthe emergence of dyskinesia associated with long-term treatment with L-DOPA. There is considerable research focus on the discovery and development of compounds that modulate glutamatergic signalling via glutamate receptors, as treatments for PD and L-DOPA-induced dyskinesia (LID). Although initial preclinical studies with ionotropic glutamate receptor antagonists showed antiparkinsonian and antidyskinetic activity, their clinical use was limited due to psychiatric adverse effects, with the exception of amantadine, a weak N-methyl-d-aspartate (NMDA) antagonist, currently used to reduce dyskinesia in PD patients. Metabotropic receptor (mGlu receptor) modulators were considered to have a more favourable side-effect profile, and several agents have been studied in preclinical models of PD. The most promising results have been seen clinically with selective antagonists of mGlu5 receptor and preclinically with selective positive allosteric modulators of mGlu4 receptor. The growing understanding of glutamate receptor crosstalk also raises the possibility of more precise modulation of glutamatergic transmission, which may lead to the development of more effective agents for PD.
Url:
DOI: 10.1155/2013/196028
PubMed: 23853735
PubMed Central: 3703788
Affiliations:
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type="wicri:Area/Ncbi/Checkpoint">001503</idno><idno type="wicri:doubleKey">2090-8083:2013:Gasparini F:metabotropic:glutamate:receptors</idno><idno type="wicri:Area/Main/Merge">000D44</idno><idno type="wicri:Area/Main/Curation">000D33</idno><idno type="wicri:Area/Main/Exploration">000D33</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Metabotropic Glutamate Receptors for Parkinson's Disease Therapy</title><author><name sortKey="Gasparini, Fabrizio" sort="Gasparini, Fabrizio" uniqKey="Gasparini F" first="Fabrizio" last="Gasparini">Fabrizio Gasparini</name><affiliation wicri:level="1"><nlm:aff id="I1">Novartis Pharma AG, Novartis Institutes for BioMedical Research Basel, Forum 1, Novartis Campus, 4056 Basel, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Novartis Pharma AG, Novartis Institutes for BioMedical Research Basel, Forum 1, Novartis Campus, 4056 Basel</wicri:regionArea><wicri:noRegion>4056 Basel</wicri:noRegion></affiliation></author><author><name sortKey="Di Paolo, Therese" sort="Di Paolo, Therese" uniqKey="Di Paolo T" first="Thérèse" last="Di Paolo">Thérèse Di Paolo</name><affiliation wicri:level="1"><nlm:aff id="I2">Neuroscience Research Unit, Centre Hospitalier Universitaire de Québec, CHUL, Quebec City, QC, Canada G1V 4G2</nlm:aff><country>Canada</country><wicri:regionArea>Neuroscience Research Unit, Centre Hospitalier Universitaire de Québec, CHUL, Quebec City, QC</wicri:regionArea><wicri:noRegion>QC</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="I3">Faculty of Pharmacy, Laval University, Quebec City, QC, Canada G1K 7P4</nlm:aff><country>Canada</country><wicri:regionArea>Faculty of Pharmacy, Laval University, Quebec City, QC</wicri:regionArea><wicri:noRegion>QC</wicri:noRegion></affiliation></author><author><name sortKey="Gomez Mancilla, Baltazar" sort="Gomez Mancilla, Baltazar" uniqKey="Gomez Mancilla B" first="Baltazar" last="Gomez-Mancilla">Baltazar Gomez-Mancilla</name><affiliation wicri:level="1"><nlm:aff id="I1">Novartis Pharma AG, Novartis Institutes for BioMedical Research Basel, Forum 1, Novartis Campus, 4056 Basel, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Novartis Pharma AG, Novartis Institutes for BioMedical Research Basel, Forum 1, Novartis Campus, 4056 Basel</wicri:regionArea><wicri:noRegion>4056 Basel</wicri:noRegion></affiliation></author></analytic><series><title level="j">Parkinson's Disease</title><idno type="ISSN">2090-8083</idno><idno type="eISSN">2042-0080</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Excessive glutamatergic signalling within the basal ganglia is implicated in the progression of Parkinson's disease (PD) and inthe emergence of dyskinesia associated with long-term treatment with L-DOPA. There is considerable research focus on the discovery and development of compounds that modulate glutamatergic signalling via glutamate receptors, as treatments for PD and L-DOPA-induced dyskinesia (LID). Although initial preclinical studies with ionotropic glutamate receptor antagonists showed antiparkinsonian and antidyskinetic activity, their clinical use was limited due to psychiatric adverse effects, with the exception of amantadine, a weak N-methyl-d-aspartate (NMDA) antagonist, currently used to reduce dyskinesia in PD patients. Metabotropic receptor (mGlu receptor) modulators were considered to have a more favourable side-effect profile, and several agents have been studied in preclinical models of PD. The most promising results have been seen clinically with selective antagonists of mGlu5 receptor and preclinically with selective positive allosteric modulators of mGlu4 receptor. The growing understanding of glutamate receptor crosstalk also raises the possibility of more precise modulation of glutamatergic transmission, which may lead to the development of more effective agents for PD.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Mercuri, Nb" uniqKey="Mercuri N">NB Mercuri</name></author><author><name sortKey="Bernardi, G" uniqKey="Bernardi G">G Bernardi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fabbrini, G" uniqKey="Fabbrini G">G Fabbrini</name></author><author><name sortKey="Brotchie, Jm" uniqKey="Brotchie J">JM Brotchie</name></author><author><name sortKey="Grandas, F" uniqKey="Grandas F">F Grandas</name></author><author><name sortKey="Nomoto, M" uniqKey="Nomoto M">M Nomoto</name></author><author><name sortKey="Goetz, Cg" uniqKey="Goetz C">CG Goetz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ahlskog, Je" 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Ward</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Johnson, Mp" uniqKey="Johnson M">MP Johnson</name></author><author><name sortKey="Nisenbaum, Es" uniqKey="Nisenbaum E">ES Nisenbaum</name></author><author><name sortKey="Large, Th" uniqKey="Large T">TH Large</name></author><author><name sortKey="Emkey, R" uniqKey="Emkey R">R Emkey</name></author><author><name sortKey="Baez, M" uniqKey="Baez M">M Baez</name></author><author><name sortKey="Kingston, Ae" uniqKey="Kingston A">AE Kingston</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Johnson, Pl" uniqKey="Johnson P">PL Johnson</name></author><author><name sortKey="Fitz, Sd" uniqKey="Fitz S">SD Fitz</name></author><author><name sortKey="Engleman, Ea" uniqKey="Engleman E">EA Engleman</name></author><author><name sortKey="Svensson, Ka" uniqKey="Svensson K">KA Svensson</name></author><author><name sortKey="Schkeryantz, Jm" uniqKey="Schkeryantz J">JM Schkeryantz</name></author><author><name sortKey="Shekhar, A" uniqKey="Shekhar A">A Shekhar</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Canada</li><li>Suisse</li></country></list><tree><country name="Suisse"><noRegion><name sortKey="Gasparini, Fabrizio" sort="Gasparini, Fabrizio" uniqKey="Gasparini F" first="Fabrizio" last="Gasparini">Fabrizio Gasparini</name></noRegion><name sortKey="Gomez Mancilla, Baltazar" sort="Gomez Mancilla, Baltazar" uniqKey="Gomez Mancilla B" first="Baltazar" last="Gomez-Mancilla">Baltazar Gomez-Mancilla</name></country><country name="Canada"><noRegion><name sortKey="Di Paolo, Therese" sort="Di Paolo, Therese" uniqKey="Di Paolo T" first="Thérèse" last="Di Paolo">Thérèse Di Paolo</name></noRegion><name sortKey="Di Paolo, Therese" sort="Di Paolo, Therese" uniqKey="Di Paolo T" first="Thérèse" last="Di Paolo">Thérèse Di Paolo</name></country></tree></affiliations></record>Pour manipuler ce document sous 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