Division of Neurology and Gerontology, Department of Internal Medicine, School of Medicine, Iwate Medical University, 19-1 Uchimaru, Morioka, Iwate 020-8505, Japan.
Neurosci Lett. 2020 Jan 1;714:134576. doi: 10.1016/j.neulet.2019.134576. Epub 2019 Oct 22.
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.
犬尿氨酸（KYN）途径在降解中枢神经系统（CNS）中负责氧化应激的分子中起着重要作用，但也可能具有神经毒性作用。3-羟基犬尿氨酸（3-HK）和喹啉酸都是该途径产生的神经毒性代谢物。在帕金森病（PD）中，氧化应激被怀疑是一种关键的致病机制。本研究旨在探讨 KYN 途径的功能以及氧化应激和神经炎症之间在 PD 中的相互作用。
参与者包括 20 名 PD 患者和 13 名对照者。采用高效液相色谱-电化学检测法测定脑脊液（CSF）中 KYN 和 3-HK 的水平。采用酶联免疫吸附法测定肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β、IL-6 和干扰素（IFN）-γ的 CSF 水平，并对 PD 患者和对照组之间的结果进行统计学比较。
PD 患者的 CSF 中 KYN 和 3-HK 的中位数分别为 49.0 nM 和 4.25 nM，对照组分别为 30.5 nM 和 1.55 nM，PD 患者的水平明显更高（p<0.05）。CSF 中测定的细胞因子水平显示，PD 患者的 TNF-α和 IL-1β水平明显高于对照组。PD 患者中 3-HK 与 TNF-α之间无正相关关系。
KYN 途径的功能障碍可能在 PD 中诱导 CNS 中的氧化应激，也可能诱导细胞因子介导的神经炎症。KYN 途径的功能改善可能有助于修饰 PD 中的神经退行性过程。
