Department of Neurology, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine of Zunyi Medical University, Zunyi, China.
Front Immunol. 2023 Oct 4;14:1253273. doi: 10.3389/fimmu.2023.1253273. eCollection 2023.
Parkinson's disease (PD) is a common neurodegenerative disorder of middle-aged and elderly people, clinically characterized by resting tremor, myotonia, reduced movement, and impaired postural balance. Clinically, patients with PD are often administered levodopa (L-DOPA) to improve their symptoms. However, after years of L-DOPA treatment, most patients experience complications of varying severity, including the "on-off phenomenon", decreased efficacy, and levodopa-induced dyskinesia (LID). The development of LID can seriously affect the quality of life of patients, but its pathogenesis is unclear and effective treatments are lacking. Glutamic acid (Glu)-mediated changes in synaptic plasticity play a major role in LID. The N-methyl-D-aspartic acid receptor (NMDAR), an ionotropic glutamate receptor, is closely associated with synaptic plasticity, and neuroinflammation can modulate NMDAR activation or expression; in addition, neuroinflammation may be involved in the development of LID. However, it is not clear whether NMDA receptors are co-regulated with neuroinflammation during LID formation. Here we review how neuroinflammation mediates the development of LID through the regulation of NMDA receptors, and assess whether common anti-inflammatory drugs and NMDA receptor antagonists may be able to mitigate the development of LID through the regulation of central neuroinflammation, thereby providing a new theoretical basis for finding new therapeutic targets for LID.
帕金森病（PD）是一种常见的中老年神经退行性疾病，临床上以静止性震颤、肌强直、运动减少和姿势平衡障碍为特征。临床上，常给予帕金森病患者左旋多巴（L-DOPA）以改善其症状。然而，经过多年的 L-DOPA 治疗，大多数患者会出现不同程度的并发症，包括“开-关现象”、疗效下降和左旋多巴诱导的运动障碍（LID）。LID 的发展会严重影响患者的生活质量，但其发病机制尚不清楚，且缺乏有效的治疗方法。谷氨酸（Glu）介导的突触可塑性变化在 LID 中起主要作用。N-甲基-D-天冬氨酸受体（NMDAR）是一种离子型谷氨酸受体，与突触可塑性密切相关，神经炎症可以调节 NMDAR 的激活或表达；此外，神经炎症可能参与 LID 的发生。然而，在 LID 形成过程中，NMDA 受体是否与神经炎症共同调节尚不清楚。本文综述了神经炎症如何通过调节 NMDA 受体介导 LID 的发生，并评估了常见的抗炎药物和 NMDA 受体拮抗剂是否可以通过调节中枢神经炎症来减轻 LID 的发生，从而为寻找 LID 的新治疗靶点提供新的理论依据。
