Changes in kynurenine pathway metabolism in Parkinson patients with L‐<scp>DOPA</scp>‐induced dyskinesia

Havelund, Jesper Foged; Andersen, Andreas Dammann; Binzer, Michael; Blaabjerg, Morten; Heegaard, Niels H H; Stenager, Egon; Færgeman, Nils J.; Gramsbergen, Jan Bert

doi:10.1111/jnc.14104

Cited by 87 publications

(81 citation statements)

References 48 publications

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“…in patients with symptoms of Parkinson's disease [56]. Low levels of norepinephrine, dopamine, homovanillic acid, serotonin, and 5-hydroxyindoleacetic acid in the blood are fixed in these patients relative to the control group [57].…”

Section: Neurological Pathology and Mental Disordersmentioning

confidence: 84%

Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology

Белобородова¹,

Grechko²,

Olenin³

2020

Metabolomics - New Insights Into Biology and Medicine

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In the twenty-first century, metabolomics allowed evaluating the profile of metabolites of various classes of compounds in the human body. The most important achievement of the metabolic approach is to obtain evidence of the intersection of human biochemical pathways and its microbiota. The effect of certain microbial metabolites on the work of key enzymes involved in the biotransformation of amino acids and other substances becomes more important in patients at risk of developing neurological and mental disorders and also contributes to the development of life-threatening conditions up to multiple organ failure after operations, injuries, and serious diseases. The authors of this chapter call the microbiota an "invisible organ," emphasizing its functional significance, and not just taxonomy, as previously thought. This chapter will discuss the mutually beneficial integration of the metabolome/microbiome in the body of healthy people and will focus on the effects of microbiota dysfunction.

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Section: Neurological Pathology and Mental Disordersmentioning

confidence: 84%

Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology

Белобородова¹,

Grechko²,

Olenin³

2020

Metabolomics - New Insights Into Biology and Medicine

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“…Among other chronic neurodegenerative disorders, a decrease in KYNA concentration was detected in brain tissue and CSF from Parkinson's disease (PD) patients [76]. However, more recent studies reported altered levels of KP metabolites in CSF from PD patients exclusively after L-DOPA treatment [77]. Dysregulation of KP was not previously reported in FTD or PSP.…”

Section: Discussionmentioning

confidence: 95%

Kynurenic Acid Levels are Increased in the CSF of Alzheimer’s Disease Patients

et al. 2020

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Kynurenic acid (KYNA) is a product of the tryptophan (TRP) metabolism via the kynurenine pathway (KP). This pathway is activated in neurodegenerative disorders, such as Alzheimer´s disease (AD). KYNA is primarily produced by astrocytes and is considered neuroprotective. Thus, altered KYNA levels may suggest an inflammatory response. Very recently, significant increases in KYNA levels were reported in cerebrospinal fluid (CSF) from AD patients compared with normal controls. In this study, we assessed the accuracy of KYNA in CSF for the classification of patients with AD, cognitively healthy controls, and patients with a variety of other neurodegenerative diseases, including frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), and progressive supranuclear palsy (PSP). Averaged KYNA concentration in CSF was higher in patients with AD when compared with healthy subjects and with all the other differentially diagnosed groups. There were no significant differences in KYNA levels in CSF between any other neurodegenerative groups and controls. These results suggest a specific increase in KYNA concentration in CSF from AD patients not seen in other neurodegenerative diseases.

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“…Disturbances of Kyn pathway metabolites in the blood of PD and AD patients are common (Widner et al 2000;Hartai et al 2007;Gulaj et al 2010;Schwarz et al 2013;Giil et al 2017;Havelund et al 2017;Chang et al 2018) but Kyn metabolites concentrations in cerebrospinal fluid (CSF), as a measure of their cerebral production, have been less well documented (Heyes et al 1992;Wennstrom et al 2014;Havelund et al 2017). In addition, with the exception of two (Giil et al 2017;Chang et al 2018), most of the abovementioned studies used a relatively small sample size and only one study analyzed Kyn metabolites in time-linked serum and CSF samples (Havelund et al 2017). To our knowledge, no study estimated the rate of transportermediated cerebral uptake of Kyn in PD or AD.…”

mentioning

confidence: 99%

Age‐ and disease‐specific changes of the kynurenine pathway in Parkinson’s and Alzheimer’s disease

Sorgdrager

Vermeiren

Faassen

et al. 2019

Journal of Neurochemistry

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The kynurenine (Kyn) pathway, which regulates neuroinflammation and N‐methyl‐d‐aspartate receptor activation, is implicated in Parkinson’s disease (PD) and Alzheimer’s disease (AD). Age‐related changes in Kyn metabolism and altered cerebral Kyn uptake along large neutral amino acid transporters, could contribute to these diseases. To gain further insight into the role and prognostic potential of the Kyn pathway in PD and AD, we investigated systemic and cerebral Kyn metabolite production and estimations of their transporter‐mediated uptake in the brain. Kyn metabolites and large neutral amino acids were retrospectively measured in serum and cerebrospinal fluid (CSF) of clinically well‐characterized PD patients (n = 33), AD patients (n = 33), and age‐matched controls (n = 39) using solid‐phase extraction‐liquid chromatographic‐tandem mass spectrometry. Aging was disease independently associated with increased Kyn, kynurenic acid and quinolinic acid in serum and CSF. Concentrations of kynurenic acid were reduced in CSF of PD and AD patients (p = 0.001; p = 0.002) but estimations of Kyn brain uptake did not differ between diseased and controls. Furthermore, serum Kyn and quinolinic acid levels strongly correlated with their respective content in CSF and Kyn in serum negatively correlated with AD disease severity (p = 0.002). Kyn metabolites accumulated with aging in serum and CSF similarly in PD patients, AD patients, and control subjects. In contrast, kynurenic acid was strongly reduced in CSF of PD and AD patients. Differential transporter‐mediated Kyn uptake is unlikely to majorly contribute to these cerebral Kyn pathway disturbances. We hypothesize that the combination of age‐ and disease‐specific changes in cerebral Kyn pathway activity could contribute to reduced neurogenesis and increased excitotoxicity in neurodegenerative disease.

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Changes in kynurenine pathway metabolism in Parkinson patients with L‐DOPA‐induced dyskinesia

Cited by 87 publications

References 48 publications

Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology

Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology

Kynurenic Acid Levels are Increased in the CSF of Alzheimer’s Disease Patients

Age‐ and disease‐specific changes of the kynurenine pathway in Parkinson’s and Alzheimer’s disease

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