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

The Kaohsiung Journal of Medical Sciences - Tập 28 - Trang 407-417 - 2012
Cornelius Rainer Pawlak1,2,3, Fu-Shih Chen4, Fu-Ying Wu5, Ying-Jui Ho6
1Department of Addictive Behavior and Addictive Medicine, Central Institute of Mental Health, Mannheim, Germany
2Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Mannheim, Germany
3Institute of Psychopharmacology, Central Institute of Mental Health, Mannheim, Germany
4Department of Pharmacy, Kaoshiung Medical University Chung-Ho Memorial Hospital, Kaoshiung, Taiwan
5General Medical Department, Shun-Tian Hospital, Taichung, Taiwan
6School of Psychology, Chung Shan Medical University Hospital, Chung Shan Medical University, Taichung, Taiwan

Tóm tắt

AbstractHyperactivation 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.

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The Kaohsiung Journal of Medical Sciences

Tập 28

407-417

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