Chronic Immune Stimulation Correlates with Reduced Phenylalanine Turnover

Neurauter, Gabriele; Schröcksnadel, Katharina; Scholl‐Bürgi, Sabine; Sperner‐Unterweger, Barbara; Schubert, Christian; Ledochowski, Maximilian; Fuchs, Dietmar

doi:10.2174/138920008785821738

Cited by 231 publications

(198 citation statements)

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“…In addition, a moderate form of hyperphenylalaninaemia is reported for patients who suffer from chronic inflammatory diseases. Notably, in such patients the increased PHE and PHE/TYR concentrations were also found to correlate with neopterin levels [17][18][19].…”

Section: Introductionmentioning

confidence: 87%

Serum tryptophan, kynurenine, phenylalanine, tyrosine and neopterin concentrations in 100 healthy blood donors

Geisler

Mayersbach²,

Becker

et al. 2015

Pteridines

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AbstractFormation of neopterin, a biomarker of the activated human immune system, is linked with tryptophan (TRP) and phenylalanine (PHE) metabolism. To obtain normal values, in this study, serum concentrations of neopterin as well as of TRP, PHE and their respective metabolites kynurenine (KYN) and tyrosine (TYR) were investigated in 100 successive blood donor serum specimens from the University Clinics of Innsbruck, Austria. In addition, nitrite concentrations were determined. Donors had passed anamnestic examination at entry and were therefore considered as healthy. The mean age of participants was 49±11.4 (mean±SD) years; 18% were older than 60 years. Both genders were included in the analysis. Neopterin concentrations measured by enzyme-linked immunosorbent assay were 5.9±1.6 nmol/L (mean±SD). Levels of amino acids and metabolites were determined by HPLC. Mean KYN and TRP concentrations were 1.78±0.42 μmol/L and 67.4±10.2 μmol/L, respectively. KYN to TRP ratio (KYN/TRP), an estimate for the activity of tryptophan-degrading enzyme indoleamine 2,3-dioxygenase, was 26.7±6.2 μmol/mmol. Mean PHE and TYR concentrations were 65.2±11.1 μmol/L and 90.6±22.9 μmol/L. PHE to TYR ratio (PHE/TYR), an estimate for the activity of PHE-converting enzyme phenylalanine hydroxylase, was 0.75±0.14 μmol/μmol. Nitrite concentrations, estimated by Griess-Ilosvay reagent, were 44.9±32.0 μmol/L. Males were taller and heavier than females (both p<0.01), but body mass index did not differ. Males presented with significantly higher TRP and TYR concentrations than females (both p<0.05). There existed significant correlations between neopterin and KYN (rs=0.368), KYN/TRP (rs=0.453), TYR (rs=–0.267; all p<0.01) and PHE/TYR (rs=0.236; p<0.05) concentrations. Data indicate that also in a population of healthy individuals an association exists between “low-grade” immune activation as is indicated by slightly higher neopterin concentrations and biochemical alterations in the amino acid metabolism. Although minor, such changes may interfere with psychoneuroimmunological regulatory networks and thus be of clinical relevance.

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Section: Introductionmentioning

confidence: 87%

Serum tryptophan, kynurenine, phenylalanine, tyrosine and neopterin concentrations in 100 healthy blood donors

Geisler

Mayersbach²,

Becker

et al. 2015

Pteridines

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“…One of the primary hypotheses is that inflammation decreases the availability of tetrahydrobiopterin (BH4). In the context of inflammation, BH4 is rapidly usurped in its role as an essential enzyme cofactor for nitric oxide synthase in the conversion of arginine to nitric oxide, an important contributor to the inflammatory response (Neurauter et al, 2008). Moreover, in the context of inflammation-induced oxidative stress, BH4 is very sensitive to being oxidized to the inactive compound dihydroxyanthopterin (Neurauter et al, 2008).…”

Section: Inflammation Effects On Neurotransmitter Metabolismmentioning

confidence: 99%

“…In the context of inflammation, BH4 is rapidly usurped in its role as an essential enzyme cofactor for nitric oxide synthase in the conversion of arginine to nitric oxide, an important contributor to the inflammatory response (Neurauter et al, 2008). Moreover, in the context of inflammation-induced oxidative stress, BH4 is very sensitive to being oxidized to the inactive compound dihydroxyanthopterin (Neurauter et al, 2008). Of relevance to dopamine as well as other monoamines, BH4 also serves as an essential cofactor for the ratelimiting enzymes that synthesize dopamine and serotonin including tyrosine hydroxylase and tryptophan hydroxylase, respectively (Neurauter et al, 2008;Felger and Miller, 2012;Haroon et al, 2012).…”

Section: Inflammation Effects On Neurotransmitter Metabolismmentioning

confidence: 99%

“…Moreover, in the context of inflammation-induced oxidative stress, BH4 is very sensitive to being oxidized to the inactive compound dihydroxyanthopterin (Neurauter et al, 2008). Of relevance to dopamine as well as other monoamines, BH4 also serves as an essential cofactor for the ratelimiting enzymes that synthesize dopamine and serotonin including tyrosine hydroxylase and tryptophan hydroxylase, respectively (Neurauter et al, 2008;Felger and Miller, 2012;Haroon et al, 2012). BH4 is also a cofactor for phenylalanine hydroxylase that converts phenylalanine to tyrosine, the primary precursor for L-DOPA that is converted to dopamine.…”

Section: Inflammation Effects On Neurotransmitter Metabolismmentioning

confidence: 99%

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Therapeutic Implications of Brain–Immune Interactions: Treatment in Translation

Miller

Haroon

Felger

2016

Neuropsychopharmacol

116

122

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A wealth of data has been amassed that details a complex, yet accessible, series of pathways by which the immune system, notably inflammation, can influence the brain and behavior. These data have opened the window to a diverse array of novel targets whose potential efficacy is tied to specific neurotransmitters and neurocircuits as well as specific behaviors. What is clear is that the impact of inflammation on the brain cuts across psychiatric disorders and engages dopaminergic and glutamatergic pathways that regulate motivation and motor activity as well as the sensitivity to threat. Given the ability to identify patient populations with increased inflammation, the precision of interventions can be further tuned, in conjunction with the ability to establish target engagement in the brain through the use of multiple neuroimaging strategies. After a brief overview of the mechanisms by which inflammation affects the brain and behavior, this review examines the extant literature on the efficacy of anti-inflammatory treatments, while forging guidelines for future intelligent clinical trial design. An examination of the most promising therapeutic strategies is also provided, along with some of the most exciting clinical trials that are currently being planned or underway.

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“…GTP-CH1 is the rate-limiting enzyme of GTP conversion into 7,8-dihydroneopterin (BH2), which leads to the production of neopterin at the expense of tetrahydrobiopterin (BH4) (Oxenkrug, 2011). BH4 is a cofactor of aromatic amino acid hydroxylase and therefore plays a fundamental role in dopamine synthesis (Neurauter et al, 2008). Cytokinesinduced GTP-CH1 activation, classically assessed by measuring increased production of neopterin, is therefore able to impair the dopaminergic neurotransmission which is known to be involved in mood disorders and cognitive dysfunctions, including in conditions of chronic immune stimulation .…”

Section: Introductionmentioning

confidence: 99%

N-3 PUFAs and neuroinflammatory processes in cognitive disorders

Leyrolle

Layé

Nadjar

2016

OCL

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-With the ageing population and increased cases of neurodegenerative diseases, there is a crucial need for the development of new nutritional approaches to prevent and delay the onset of cognitive decline. Neuroinflammatory processes contribute to neuronal damage that underpins neurodegenerative disorders. Growing evidence sheds light on the use of dietary n-3 long chain polyunsaturated fatty acids to improve cognitive performances and reduce the neuroinflammatory responses occurring with age and neurodegenerative pathologies. This review will summarise the most recent information related to the impact and mechanisms underlying the neuroinflammatory processes in cognitive disorders. We will also discuss the mechanisms underlying n-3 polyunsaturated fatty acids effect on neuroinflammation and memory decline.Keywords: Neuroinflammation / microglia / n-3 polyunsaturated fatty acids / cognitive disorders / Alzheimer disease Résumé -Acides gras polyinsaturés de la famille des oméga 3, processus neuroinflammatoires et troubles cognitifs. Le développement d'approches nutritionnelles pertinentes pour prévenir et retarder l'apparition du déclin cognitif est un enjeu important, compte tenu du vieillissement de la population et de l'augmentation de l'incidence des maladies neurodégénératives. Les processus neuro-inflammatoires contribuent aux mécanismes neuropathologiques impliqués dans les troubles neurodégénératifs et de la cognition. Des données récentes indiquent l'importance des acides gras polyinsaturés n-3 alimentaires dans le maintien des performances mnésiques et la régulation de la neuroinflammation liée à l'âge ou à la maladie d'Alzheimer. Dans cette revue, seront présentées des données récentes sur les liens existants entre le statut nutritionnel en acides gras polyinsaturés n-3, les processus neuro-inflammatoires et les troubles cognitifs associés, ainsi que les mécanismes qui pourraient être impliqués dans les effets protecteurs de ces acides gras.

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Chronic Immune Stimulation Correlates with Reduced Phenylalanine Turnover

Cited by 231 publications

References 0 publications

Serum tryptophan, kynurenine, phenylalanine, tyrosine and neopterin concentrations in 100 healthy blood donors

Serum tryptophan, kynurenine, phenylalanine, tyrosine and neopterin concentrations in 100 healthy blood donors

Therapeutic Implications of Brain–Immune Interactions: Treatment in Translation

N-3 PUFAs and neuroinflammatory processes in cognitive disorders

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