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

Abstract

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.

P7C3 Inhibits LPS-Induced Microglial Activation to Protect Dopaminergic Neurons Against Inflammatory Factor-Induced Cell Death in vitro and in vivo

“…LPS-induced inflammatory neurotoxicity depends mainly on the excessive production of pro-inflammatory factors including iNOS, COX-2, IL-6, TNF-α by microglia (Okun et al, 2009 ; Liu and Bing, 2011 ). The inhibitors of iNOS and COX-2 have neuroprotective effects by suppressing microglial activation and inflammatory damage (Li et al, 2003 ; Pawlak et al, 2012 ; Xia et al, 2015 ). TNFα and IL-6 play central roles in initiating and regulating the cytokine cascade in inflammatory response (Brown and Neher, 2010 ).…”

Post-operative cognitive dysfunction: pre-operative risk assessment and peri-operative risk minimization: A pragmatic review of the literature

“…It is increasingly understood that the immune system and inflammatory mediators have a key role in the formation of memory and learning, and that their dysregulation has a role in the pathogenesis of cognitive dysfunction [35,36]. Current evidence demonstrates that most neurodegenerative disorders have an inflammatory component; including both acute pathological conditions, such as traumatic brain injury and stroke, and chronic conditions, such as epilepsy, Alzheimer's disease, Parkinson's disease, and ageing [37,38].…”