Kynurenines and aerobic exercise capacity in chronic kidney disease: A cross-sectional and longitudinal study.

Background: The causes of reduced aerobic exercise capacity (ExCap) in chronic kidney disease (CKD) are multifactorial, possibly involving the accumulation of tryptophan (TRP) metabolites such as kynurenine (KYN) and kynurenic acid (KYNA), known as kynurenines. Their relationship to ExCap has yet to be studied in CKD. We hypothesised that aerobic ExCap would be negatively associated with plasma levels of TRP, KYN and KYNA in CKD.

Central and peripheral kynurenine pathway metabolites in COVID-19: Implications for neurological and immunological responses.

Long-term symptoms such as pain, fatigue, and cognitive impairments are commonly observed in individuals affected by coronavirus disease 2019 (COVID-19). Metabolites of the kynurenine pathway have been proposed to account for cognitive impairment in COVID-19 patients. Here, cerebrospinal fluid (CSF) and plasma levels of kynurenine pathway metabolites in 53 COVID-19 patients and 12 non-inflammatory neurological disease controls in Sweden were measured with an ultra-performance liquid chromatography-tandem mass spectrometry system (UPLC-MS/MS) and correlated with immunological markers and neurological markers.

Neuroactive Kynurenines as Pharmacological Targets: New Experimental Tools and Exciting Therapeutic Opportunities.

Both preclinical and clinical studies implicate functional impairments of several neuroactive metabolites of the kynurenine pathway (KP), the major degradative cascade of the essential amino acid tryptophan in mammals, in the pathophysiology of neurologic and psychiatric diseases. A number of KP enzymes, such as tryptophan 2,3-dioxygenase (TDO2), indoleamine 2,3-dioxygenases (IDO1 and IDO2), kynurenine aminotransferases (KATs), kynurenine 3-monooxygenase (KMO), 3-hydroxyanthranilic acid oxygenase (3-HAO), and quinolinic acid phosphoribosyltransferase (QPRT), control brain KP metabolism in health and disease and are therefore increasingly considered to be promising targets for the treatment of disorders of the nervous system. Understanding the distribution, cellular expression, and regulation of KP enzymes and KP metabolites in the brain is therefore critical for the conceptualization and implementation of successful therapeutic strategies.

The Tryptophan Metabolite Indole-3-Propionic Acid Raises Kynurenic Acid Levels in the Rat Brain In Vivo.

Alterations in the composition of the gut microbiota may be causally associated with several brain diseases. Indole-3-propionic acid (IPrA) is a tryptophan-derived metabolite, which is produced by intestinal commensal microbes, rapidly enters the circulation, and crosses the blood-brain barrier. IPrA has neuroprotective properties, which have been attributed to its antioxidant and bioenergetic effects.

Mood, Cognitive Function, and Plasma Kynurenine Metabolites Responses Following Severe Changes in Physical Activity.

Purpose: To monitor changes in mood, cognitive function, brain electrical activity, and circulating kynurenine pathway metabolites in response to a 3-wk severe physical activity (PA) restriction, followed by 3 wk of resumed activity adding resistance and high-intensity interval exercise training.

Methods: Twenty healthy participants (14 males, 6 females; 25.4 ± 5.