Targeting NR2A-containing NMDA receptors reduces L-DOPA-induced dyskinesias

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• 作者：Fabrizio Gardoni ; Carmelo Sgobio ; Valentina Pendolino ; Paolo Calabresi ; Monica Di Luca ; Barbara Picconi
• 关键词：Synaptic plasticity ; Dopamine ; Striatum ; Parkinson's disease ; Dyskinesias ; NMDA receptor ; Cell-permeable peptides
• 刊名：Neurobiology of Aging
• 出版年：2012
• 出版时间：September, 2012
• 年：2012
• 卷：33
• 期：9
• 页码：2138-2144
• 全文大小：1311 K

文摘

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.