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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
11
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pubmed:dateCreated |
2006-3-16
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pubmed:abstractText |
Abnormal function of NMDA receptor has been suggested to be correlated with the pathogenesis of Parkinson's disease (PD) as well as with the development of l-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia. Here we show that NMDA receptor NR2 subunits display specific alterations of their subcellular distribution in striata from unilateral 6-hydroxydopamine-lesioned, L-DOPA-treated dyskinetic, and L-DOPA-treated nondyskinetic rats. Dyskinetic animals have significantly higher levels of NR2A subunit in the postsynaptic compartment than all other experimental groups, whereas NR2B subunit shows a significant reduction in both dopamine-denervated and dyskinetic rats. These events are paralleled by profound modifications of NMDA receptor NR2B subunit association with interacting elements, i.e., members of the membrane-associated guanylate kinase (MAGUK) protein family postsynaptic density-95, synapse-associated protein-97 and synapse-associated protein-102. Treatment of nondyskinetic animals with a synthetic peptide (TAT2B) able to affect NR2B binding to MAGUK proteins as well as synaptic localization of this subunit in nondyskinetic rats was sufficient to induce a shift of treated rats toward a dyskinetic motor behavior. These data indicate abnormal NR2B redistribution between synaptic and extrasynaptic membranes as an important molecular disturbance of the glutamatergic synapse involved in L-DOPA-induced dyskinesia.
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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/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Antiparkinson Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Calmodulin-Dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Calmodulin-Dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/Dlgh1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Dlgh3 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Dlgh4 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Levodopa,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/NR2A NMDA receptor,
http://linkedlifedata.com/resource/pubmed/chemical/NR2B NMDA receptor,
http://linkedlifedata.com/resource/pubmed/chemical/Neuropeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Oxidopamine,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, N-Methyl-D-Aspartate,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1529-2401
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
26
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2914-22
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16540568-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:16540568-Animals,
pubmed-meshheading:16540568-Antiparkinson Agents,
pubmed-meshheading:16540568-Calcium-Calmodulin-Dependent Protein Kinase Type 2,
pubmed-meshheading:16540568-Calcium-Calmodulin-Dependent Protein Kinases,
pubmed-meshheading:16540568-Corpus Striatum,
pubmed-meshheading:16540568-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:16540568-Levodopa,
pubmed-meshheading:16540568-Male,
pubmed-meshheading:16540568-Membrane Proteins,
pubmed-meshheading:16540568-Motor Activity,
pubmed-meshheading:16540568-Neuropeptides,
pubmed-meshheading:16540568-Oxidopamine,
pubmed-meshheading:16540568-Parkinsonian Disorders,
pubmed-meshheading:16540568-Phosphorylation,
pubmed-meshheading:16540568-Protein Binding,
pubmed-meshheading:16540568-Protein Interaction Mapping,
pubmed-meshheading:16540568-Protein Processing, Post-Translational,
pubmed-meshheading:16540568-Protein Structure, Tertiary,
pubmed-meshheading:16540568-Protein Transport,
pubmed-meshheading:16540568-Protein-Tyrosine Kinases,
pubmed-meshheading:16540568-Psychomotor Performance,
pubmed-meshheading:16540568-Rats,
pubmed-meshheading:16540568-Rats, Wistar,
pubmed-meshheading:16540568-Receptors, N-Methyl-D-Aspartate,
pubmed-meshheading:16540568-Recombinant Fusion Proteins,
pubmed-meshheading:16540568-Subcellular Fractions,
pubmed-meshheading:16540568-Synapses
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pubmed:year |
2006
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pubmed:articleTitle |
A critical interaction between NR2B and MAGUK in L-DOPA induced dyskinesia.
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pubmed:affiliation |
Center of Excellence on Neurodegenerative Diseases, Department of Pharmacological Sciences, University of Milan, 20133 Milan, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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