Dipartimento Scienze Farmacologiche, Università degli Studi di Milano, Milano, Italy.
Neurobiol Aging. 2012 Sep;33(9):2138-44. doi: 10.1016/j.neurobiolaging.2011.06.019. Epub 2011 Aug 6.
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.
左旋多巴（L-DOPA）诱导的运动障碍是帕金森病（PD）治疗中临床应用的治疗策略的主要副作用。左旋多巴治疗的第一个有益的“蜜月”阶段之后是恶化阶段，在此阶段，左旋多巴的给药会导致药物疗效的运动波动（“开-关”状态）和运动障碍。N-甲基-D-天冬氨酸（NMDA）受体的组成和功能的改变是描述在运动障碍的实验模型中的纹状体突触变化的主要原因之一。在本研究中，通过在运动障碍的发展过程中使用针对 NR2A 亚基的细胞渗透性肽来调节突触 NMDA 受体的组成，导致帕金森病大鼠中出现运动障碍的比例降低。
