摘要

Hyperactivation of glutamatergic N-methyl-D-aspartate (NMDA) receptors has been implicated in the excitotoxicity and pathophysiology of Parkinson%26apos;s disease (PD). NMDA receptor blockers have been used clinically to treat dementia, but their efficacy is controversial. Modulation of NMDA receptors might improve neuroinfiammation 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 neuroinfiammation 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.

  • 出版日期2012-8
  • 单位上海市精神卫生中心