Altered tryptophan metabolism in Parkinson's disease: A possible novel therapeutic approach

Szabó, Nikoletta; Kincses, Zsigmond Tamás; Toldi, József; Vécsei, László

doi:10.1016/j.jns.2011.07.021

Cited by 65 publications

(40 citation statements)

References 82 publications

(78 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Disrupted tryptophan metabolism has been demonstrated in several neurological disorders, including in PD (McCusker et al 2014;Szabo et al 2011). Our metabolomics data suggest that further studies investigating effects of ATR on tryptophan metabolism in the brain, especially focused on several critical intermediates, including quinolinic acid, 3-hydroxy kynurenine, and kynurenic acid are needed.…”

Section: Discussionmentioning

confidence: 86%

“…Some of tryptophan's intermediate metabolites, i.e., quinolinic acid and 3-hydroxy kynurenine, are neurotoxic, while others, such as kynurenic acid, are potentially neuroprotective (Szabo et al 2011). Disrupted tryptophan metabolism has been demonstrated in several neurological disorders, including in PD (McCusker et al 2014;Szabo et al 2011).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Short-term oral atrazine exposure alters the plasma metabolome of male C57BL/6 mice and disrupts α-linolenate, tryptophan, tyrosine and other major metabolic pathways

Lin

Roede

et al. 2014

Toxicology

View full text Add to dashboard Cite

, N. M. (2014). Short-term oral atrazine exposure alters the plasma metabolome of male C57BL/6 mice and disrupts α -linolenate, tryptophan, tyrosine and other major metabolic pathways. Retrieved from http://krex.ksu.edu Published Version InformationCitation: Lin, Z., Roede, J. R., He, C., Jones, D. P., & Filipov, N. M. (2014). Short-term oral atrazine exposure alters the plasma metabolome of male C57BL/6 mice and disrupts α -linolenate, tryptophan, tyrosine and other major metabolic pathways. Toxicology, 326, 130-141. adult male C57BL/6 mice, the present study aimed to investigate effects of a 10-day oral ATR exposure (0, 5, 25, 125, or 250 mg/kg) on the mouse plasma metabolome and to determine metabolic pathways affected by ATR that may be reflective of ATR's effects on the brain and useful to identify peripheral biomarkers of neurotoxicity. Four h after the last dosing on day 10, plasma was collected and analyzed with high-performance, dual chromatography-Fouriertransform mass spectrometry that was followed by biostatistical and bioinformatic analyses. CopyrightATR exposure (≥5 mg/kg) significantly altered plasma metabolite profile and resulted in a dosedependent increase in the number of metabolites with ion intensities significantly different from the control group. Pathway analyses revealed that ATR exposure strongly correlated with and disrupted multiple metabolic pathways. Tyrosine, tryptophan, linoleic acid and α-linolenic acid metabolic pathways were among the affected pathways, with α-linolenic acid metabolism being affected to the greatest extent. Observed effects of ATR on plasma tyrosine and tryptophan metabolism may be reflective of the previously reported perturbations of brain dopamine and serotonin homeostasis, respectively. ATR-caused alterations in the plasma profile of α-linolenic acid metabolism are a potential novel and sensitive plasma biomarker of ATR effect and plasma metabolomics could be used to better assess the risks, including to the brain, associated with ATR overexposure.

show abstract

Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Short-term oral atrazine exposure alters the plasma metabolome of male C57BL/6 mice and disrupts α-linolenate, tryptophan, tyrosine and other major metabolic pathways

Lin

Roede

et al. 2014

Toxicology

View full text Add to dashboard Cite

show abstract

“…Important to know, kynurenine pathway abnormalities have been reported in migraine (74) and PD (76). Chronic migraine patients have shown astonishing elevation of anthranilic acid as well as xanthurenic acid, to a moderate extent, with a decline in all other kynurenines (74).…”

Section: Riboflavin As a Determinant Of The Kynurenine Pathwaymentioning

confidence: 99%

Riboflavin Has Neuroprotective Potential: Focus on Parkinson’s Disease and Migraine

Marashly

Bohlega

2017

Front. Neurol.

View full text Add to dashboard Cite

With the huge negative impact of neurological disorders on patient’s life and society resources, the discovery of neuroprotective agents is critical and cost-effective. Neuroprotective agents can prevent and/or modify the course of neurological disorders. Despite being underestimated, riboflavin offers neuroprotective mechanisms. Significant pathogenesis-related mechanisms are shared by, but not restricted to, Parkinson’s disease (PD) and migraine headache. Those pathogenesis-related mechanisms can be tackled through riboflavin proposed neuroprotective mechanisms. In fact, it has been found that riboflavin ameliorates oxidative stress, mitochondrial dysfunction, neuroinflammation, and glutamate excitotoxicity; all of which take part in the pathogenesis of PD, migraine headache, and other neurological disorders. In addition, riboflavin-dependent enzymes have essential roles in pyridoxine activation, tryptophan-kynurenine pathway, and homocysteine metabolism. Indeed, pyridoxal phosphate, the active form of pyridoxine, has been found to have independent neuroprotective potential. Also, the produced kynurenines influence glutamate receptors and its consequent excitotoxicity. In addition, methylenetetrahydrofolate reductase requires riboflavin to ensure normal folate cycle influencing the methylation cycle and consequently homocysteine levels which have its own negative neurovascular consequences if accumulated. In conclusion, riboflavin is a potential neuroprotective agent affecting a wide range of neurological disorders exemplified by PD, a disorder of neurodegeneration, and migraine headache, a disorder of pain. In this article, we will emphasize the role of riboflavin in neuroprotection elaborating on its proposed neuroprotective mechanisms in opposite to the pathogenesis-related mechanisms involved in two common neurological disorders, PD and migraine headache, as well as, we encourage the clinical evaluation of riboflavin in PD and migraine headache patients in the future.

show abstract

“…It decreases during epilepsy (Kamiński et al, 2003), Parkinson's disease (Oqawa et al, 1992; Szabó et al, 2011), and Huntington's disease (Beal et al, 1992, 1990), whereas it increases during schizophrenia (Schwarcz et al, 2001; Nilsson et al, 2005; Linderholm et al, 2012) and Alzheimer's disease (Baran et al, 1999; Gong et al, 2011). …”

Section: Introductionmentioning

confidence: 99%

Systemic L-Kynurenine sulfate administration disrupts object recognition memory, alters open field behavior and decreases c-Fos immunopositivity in C57Bl/6 mice

Varga

Herédi

Kánvási

et al. 2015

Front. Behav. Neurosci.

Self Cite

View full text Add to dashboard Cite

L-Kynurenine (L-KYN) is a central metabolite of tryptophan degradation through the kynurenine pathway (KP). The systemic administration of L-KYN sulfate (L-KYNs) leads to a rapid elevation of the neuroactive KP metabolite kynurenic acid (KYNA). An elevated level of KYNA may have multiple effects on the synaptic transmission, resulting in complex behavioral changes, such as hypoactivity or spatial working memory deficits. These results emerged from studies that focused on rats, after low-dose L-KYNs treatment. However, in several studies neuroprotection was achieved through the administration of high-dose L-KYNs. In the present study, our aim was to investigate whether the systemic administration of a high dose of L-KYNs (300 mg/bwkg; i.p.) would produce alterations in behavioral tasks (open field or object recognition) in C57Bl/6j mice. To evaluate the changes in neuronal activity after L-KYNs treatment, in a separate group of animals we estimated c-Fos expression levels in the corresponding subcortical brain areas. The L-KYNs treatment did not affect the general ambulatory activity of C57Bl/6j mice, whereas it altered their moving patterns, elevating the movement velocity and resting time. Additionally, it seemed to increase anxiety-like behavior, as peripheral zone preference of the open field arena emerged and the rearing activity was attenuated. The treatment also completely abolished the formation of object recognition memory and resulted in decreases in the number of c-Fos-immunopositive-cells in the dorsal part of the striatum and in the CA1 pyramidal cell layer of the hippocampus. We conclude that a single exposure to L-KYNs leads to behavioral disturbances, which might be related to the altered basal c-Fos protein expression in C57Bl/6j mice.

show abstract

Altered tryptophan metabolism in Parkinson's disease: A possible novel therapeutic approach

Cited by 65 publications

References 82 publications

Short-term oral atrazine exposure alters the plasma metabolome of male C57BL/6 mice and disrupts α-linolenate, tryptophan, tyrosine and other major metabolic pathways

Short-term oral atrazine exposure alters the plasma metabolome of male C57BL/6 mice and disrupts α-linolenate, tryptophan, tyrosine and other major metabolic pathways

Riboflavin Has Neuroprotective Potential: Focus on Parkinson’s Disease and Migraine

Systemic L-Kynurenine sulfate administration disrupts object recognition memory, alters open field behavior and decreases c-Fos immunopositivity in C57Bl/6 mice

Contact Info

Product

Resources

About