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Impaired metabolism of kynurenine and its metabolites in CSF of parkinson's disease
- Source :
- Neuroscience letters. 714
- Publication Year :
- 2019
-
Abstract
- The kynurenine (KYN) pathway plays an important role in degrading molecules responsible for oxidative stress in the central nervous system (CNS), but can also have neurotoxic effects. Both 3-hydroxykynurenine (3-HK) and quinolinic acid are neurotoxic metabolites produced from this pathway. In Parkinson's disease (PD), oxidative stress is suspected to represent a key pathogenic mechanism. This study aimed to investigate the function of the KYN pathway and interactions between oxidative stress and neuroinflammation in PD.Participants comprised 20 patients with PD and 13 controls. Cerebrospinal fluid (CSF) levels of KYN and 3-HK were measured using high-performance liquid chromatography coupled with an electrochemical detector. CSF levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and interferon (IFN)-γ were measured with an enzyme-linked immunosorbent assay, and results were statistically compared between PD patients and controls.Median CSF levels of KYN and 3-HK were 49.0 nM and 4.25 nM in PD and 30.5 nM and 1.55 nM in controls, respectively, showing significantly higher levels in PD (p 0.05). CSF levels of measured cytokines showed that TNF-α and IL-1β were significantly higher in PD patients than in controls. No positive correlation between 3-HK and TNF-α was seen in PD.Dysfunction of the KYN pathway may induce oxidative stress in the CNS in PD, and may also induce cytokine-mediated neuroinflammation. Functional amelioration of the KYN pathway may facilitate modification of neurodegenerative processes in PD.
- Subjects :
- 0301 basic medicine
Male
Parkinson's disease
Kynurenine pathway
Interleukin-1beta
Pharmacology
medicine.disease_cause
03 medical and health sciences
chemistry.chemical_compound
Interferon-gamma
0302 clinical medicine
Medicine
Humans
Neuroinflammation
Kynurenine
Aged
Inflammation
business.industry
Interleukin-6
Tumor Necrosis Factor-alpha
General Neuroscience
Interleukin
Parkinson Disease
Middle Aged
medicine.disease
Oxidative Stress
030104 developmental biology
chemistry
Case-Control Studies
Cytokines
Tumor necrosis factor alpha
Female
business
030217 neurology & neurosurgery
Oxidative stress
Metabolic Networks and Pathways
Quinolinic acid
Subjects
Details
- ISSN :
- 18727972
- Volume :
- 714
- Database :
- OpenAIRE
- Journal :
- Neuroscience letters
- Accession number :
- edsair.doi.dedup.....78576241fd5fad3af940ba1e570447a4