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.
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.
Department of Addictive Behavior and Addictive Medicine, Central Institute of Mental Health, Mannheim, Germany.
Cornelius Rainer
CR
Pawlak
Fu-Shih
FS
Chen
Fu-Ying
FY
Wu
Ying-Jui
YJ
Ho
D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use; D003523:Cycloserine / Q000627:therapeutic use*; D006801:Humans; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
D052246:Cyclooxygenase 2 Inhibitors; D016194:Receptors, N-Methyl-D-Aspartate; D003523:Cycloserine; D051546:Cyclooxygenase 2