title: Targeting NR2A-containing NMDA receptors reduces L-DOPA-induced dyskinesias.
abstract: Levodopa (L-DOPA)-induced dyskinesias represent the main side effect of the therapeutic strategy clinically used in Parkinson's disease (PD) treatment. The first beneficial "honeymoon" phase of L-DOPA therapy is followed by a phase of deterioration in which L-DOPA administration causes motor fluctuations in the drug efficacy ("on-off" state) and dyskinesias. Alterations of the composition and function of N-methyl-D-aspartate (NMDA) receptor represent one of the main causes for the striatal synaptic changes described in experimental model of dyskinesias. In the present study, the modulation of the composition of synaptic NMDA receptor by using a cell-permeable peptide targeting NR2A subunit during the development of dyskinesias led to a reduction of the percentage of parkinsonian rats developing dyskinetic movements.
authors.affiliation: Dipartimento Scienze Farmacologiche, Università degli Studi di Milano, Milano, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Gardoni
authors.forename: Carmelo
authors.initials: C
authors.lastname: Sgobio
authors.forename: Valentina
authors.initials: V
authors.lastname: Pendolino
authors.forename: Paolo
authors.initials: P
authors.lastname: Calabresi
authors.forename: Monica
authors.initials: M
authors.lastname: Di Luca
authors.forename: Barbara
authors.initials: B
authors.lastname: Picconi
mesh_terms: D018663:Adrenergic Agents / Q000633:toxicity; D000704:Analysis of Variance; D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D004195:Disease Models, Animal; D000076122:Disks Large Homolog 4 Protein; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007980:Levodopa / Q000009:adverse effects*; D008297:Male; D008474:Medial Forebrain Bundle / Q000187:drug effects / Q000503:physiopathology; D008565:Membrane Proteins / Q000378:metabolism; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000188:drug therapy / Q000209:etiology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013347:Subcellular Fractions; D013997:Time Factors
chemical_list: D018663:Adrenergic Agents; D000978:Antiparkinson Agents; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C120997:NR2A NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D007980:Levodopa; D016627:Oxidopamine; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2