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首页> 外文期刊>Kaohsiung Journal of Medical Sciences >Potential of D-cycloserine in the treatment of behavioral and neuroinflammatory disorders in Parkinson's disease and studies that need to be performed before clinical trials
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Potential of D-cycloserine in the treatment of behavioral and neuroinflammatory disorders in Parkinson's disease and studies that need to be performed before clinical trials

机译：D-环丝氨酸在治疗帕金森氏病行为和神经炎性疾病中的潜力以及需要在临床试验之前进行的研究

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摘要

Hyperactivation of glutamatergic N-methyl-D-aspartate (NMDA) receptors has been implicated in the excitotoxicity and pathophysiology of Parkinson's disease (PD). NMDA receptor blockers have been used clinically to treat dementia, but their efficacy is controversial. Modulation of NMDA receptors might improve neuroinflammation and cognitive deficits in PD. D-cycloserine (DCS), a partial agonist binding to the glycine binding site of NMDA receptors, has been demonstrated to improve cognitive function in primates and rodents. Our previous study showed that DCS can reduce motor, emotional, and cognitive dysfunctions, as well as neuroinflammation and neurodegeneration in a PD animal model and may therefore have potential for the treatment of neuroinflammation and cognitive dysfunction in patients with PD. In addition, increased expression of cyclooxygenase type-2 (COX-2) has been observed in dopaminergic neurons and activated microglia in the brain of both PD patients and PD animal models. COX-2 inhibitors can suppress activation of microglia and protect dopaminergic neurons from degeneration. Thus, a combination of DCS and COX-2 inhibitors might prove useful in suppressing neuroinflammation and cognitive deficits in PD.
机译：谷氨酸能的N-甲基-D-天冬氨酸（NMDA）受体的过度活化与帕金森氏病（PD）的兴奋性毒性和病理生理学有关。 NMDA受体阻滞剂已在临床上用于治疗痴呆症，但其疗效尚存争议。 NMDA受体的调节可能会改善PD中的神经炎症和认知功能障碍。 D-环丝氨酸（DCS）是与NMDA受体的甘氨酸结合位点结合的部分激动剂，已被证明可以改善灵长类动物和啮齿动物的认知功能。我们以前的研究表明，DCS可以减少PD动物模型中的运动，情绪和认知功能障碍以及神经炎症和神经退行性变，因此可能具有治疗PD患者的神经炎症和认知功能障碍的潜力。另外，在PD患者和PD动物模型的脑中，在多巴胺能神经元和活化的小胶质细胞中都观察到了环氧合酶2型（COX-2）的表达增加。 COX-2抑制剂可抑制小胶质细胞的活化并保护多巴胺能神经元免于变性。因此，DCS和COX-2抑制剂的组合可能被证明可用于抑制PD中的神经炎症和认知缺陷。

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