Peripheral Tryptophan – Kynurenine Metabolism Associated with Metabolic Syndrome is Different in Parkinson’s and Alzheimer’s Diseases

Oxenkrug, Gregory F.; M, van der Hart; Roeser, Julien; Summergrad, Paul

doi:10.31038/edmj.2017141

Cited by 22 publications

(4 citation statements)

References 43 publications

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“…In the present study, we observed a relevant increase in KYN serum concentration in the VitD group after vitamin D 3 administration. Our results are in line with a study conducted in 2017 [26], where the authors demonstrated higher KYN concentrations in patients with PD compared with healthy controls. However, other results are in contrast-lower KYN concentrations were observed in PD patients than in the control group [27].…”

Section: Discussionsupporting

confidence: 93%

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Impact of 12 Weeks of Vitamin D3 Administration in Parkinson’s Patients with Deep Brain Stimulation on Kynurenine Pathway and Inflammatory Status

Bytowska,

Korewo-Labelle,

Kowalski

et al. 2023

Nutrients

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The current study aimed to investigate whether a 12-week Body Mass Index (BMI)-based (the higher the BMI, the higher the dosage) vitamin D3 administration may affect both the kynurenine pathway (KP) and the inflammatory state in Parkinson’s disease (PD) patients with deep brain stimulation (DBS) and may be useful for developing novel therapeutic targets against PD. Patients were randomly assigned to two groups: supplemented with vitamin D3 (VitD, n = 15) and treated with vegetable oil (PL, n = 21). Administration lasted for 12 weeks. The isotope dilution method by LC-MS/MS was applied to measure KP and vitamin D metabolites. Serum concentrations of cytokines such as IL-6 and TNF-α were measured using ELISA kits. After administration, the serum concentration of TNF-α decreased in PD patients with DBS. Moreover, in KP: 3-hydroksykynurenine (3-HK) was increased in the PL group, picolinic acid was decreased in the PL group, and kynurenic acid tended to be higher after administration. Furthermore, a negative correlation between 3-HK and 25(OH)D3 and 24,25(OH)2D3 was noticed. Our preliminary results provide further evidence regarding a key link between the KP substances, inflammation status, and metabolites of vitamin D in PD patients with DBS. These findings may reflect the neuroprotective abilities of vitamin D3 in PD patients with DBS.

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Section: Discussionsupporting

confidence: 93%

“…KYNA concentrations are lower in PD patients than in healthy controls [27][28][29]. Nonetheless, some authors reported increased concentrations of KYNA in PD [26]. This indicates that the results are inconsistent among researchers of PD.…”

Section: Discussionmentioning

confidence: 95%

Impact of 12 Weeks of Vitamin D3 Administration in Parkinson’s Patients with Deep Brain Stimulation on Kynurenine Pathway and Inflammatory Status

Bytowska,

Korewo-Labelle,

Kowalski

et al. 2023

Nutrients

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“…Anthranilic acid is often seen as part of the neurotoxic branch of the kynurenine pathway, a branch that includes quinolinic acid and hydroxykynurenine [ 187 , 188 ]. Elevated serum levels of anthranilic acid have been measured in people with schizophrenia and in those diagnosed with Parkinson’s disease [ 184 , 189 , 190 ]. Oxenkrug and colleagues showed circulating anthranilic acid levels in patients with schizophrenia were two times higher than those of the control population, confirming the results of a previous rat model study [ 184 ].…”

Section: Anthranilic Acid and Beyondmentioning

confidence: 99%

Microbial-Derived Tryptophan Metabolites and Their Role in Neurological Disease: Anthranilic Acid and Anthranilic Acid Derivatives

2023

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The gut microbiome provides the host access to otherwise indigestible nutrients, which are often further metabolized by the microbiome into bioactive components. The gut microbiome can also shift the balance of host-produced compounds, which may alter host health. One precursor to bioactive metabolites is the essential aromatic amino acid tryptophan. Tryptophan is mostly shunted into the kynurenine pathway but is also the primary metabolite for serotonin production and the bacterial indole pathway. Balance between tryptophan-derived bioactive metabolites is crucial for neurological homeostasis and metabolic imbalance can trigger or exacerbate neurological diseases. Alzheimer’s, depression, and schizophrenia have been linked to diverging levels of tryptophan-derived anthranilic, kynurenic, and quinolinic acid. Anthranilic acid from collective microbiome metabolism plays a complex but important role in systemic host health. Although anthranilic acid and its metabolic products are of great importance for host–microbe interaction in neurological health, literature examining the mechanistic relationships between microbial production, host regulation, and neurological diseases is scarce and at times conflicting. This narrative review provides an overview of the current understanding of anthranilic acid’s role in neurological health and disease, with particular focus on the contribution of the gut microbiome, the gut–brain axis, and the involvement of the three major tryptophan pathways.

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“…Metabolomic studies have identified increased alanine and phenylalanine [ 292 ] and reduced tryptophan in PD brains [ 293 ]. Dysregulation of the kynurenine pathway—a metabolite derived from tryptophan—was found in PD [ 294 , 295 , 296 ], providing potential novel biomarker candidates for investigating the pathogenesis of PD and suggesting new therapeutic strategies [ 294 ]. This study confirmed the pioneering research of M. Flint Beal on decreased kynurenine in neurodegenerative disorders [ 297 ].…”

Section: Metabolic Alterations In Ad and Pd Brainsmentioning

confidence: 99%

Metabolic Features of Brain Function with Relevance to Clinical Features of Alzheimer and Parkinson Diseases

et al. 2022

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Brain metabolism is comprised in Alzheimer’s disease (AD) and Parkinson’s disease (PD). Since the brain primarily relies on metabolism of glucose, ketone bodies, and amino acids, aspects of these metabolic processes in these disorders—and particularly how these altered metabolic processes are related to oxidative and/or nitrosative stress and the resulting damaged targets—are reviewed in this paper. Greater understanding of the decreased functions in brain metabolism in AD and PD is posited to lead to potentially important therapeutic strategies to address both of these disorders, which cause relatively long-lasting decreased quality of life in patients.

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Peripheral Tryptophan – Kynurenine Metabolism Associated with Metabolic Syndrome is Different in Parkinson’s and Alzheimer’s Diseases

Cited by 22 publications

References 43 publications

Impact of 12 Weeks of Vitamin D3 Administration in Parkinson’s Patients with Deep Brain Stimulation on Kynurenine Pathway and Inflammatory Status

Impact of 12 Weeks of Vitamin D3 Administration in Parkinson’s Patients with Deep Brain Stimulation on Kynurenine Pathway and Inflammatory Status

Microbial-Derived Tryptophan Metabolites and Their Role in Neurological Disease: Anthranilic Acid and Anthranilic Acid Derivatives

Metabolic Features of Brain Function with Relevance to Clinical Features of Alzheimer and Parkinson Diseases

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