KYNURENINES IN THE MAMMALIAN BRAIN: WHEN PHYSIOLOGY MEETS PATHOLOGY

By R. Schwarcz, J. Bruno, P. Muchowski, H. Wu. Nature Reviews Neuroscience, 2012

1,425 citations recorded by the source corpus.

The essential amino acid tryptophan is not only a precursor of serotonin but is also degraded to several other neuroactive compounds, including kynurenic acid, 3-hydroxykynurenine and quinolinic acid. The synthesis of these metabolites is regulated by an enzymatic cascade, known as the kynurenine pathway, that is tightly controlled by the immune system. Dysregulation of this pathway, resulting in hyper- or hypofunction of active metabolites, is associated with neurodegenerative and other neurological disorders, as well as with psychiatric diseases such as depression and schizophrenia. With recently developed pharmacological agents, it is now possible to restore metabolic equilibrium and envisage novel therapeutic interventions.

Subfields: Behavioral Neuroscience, Biological Psychiatry, Psychiatry and Mental health

View Paper: https://www.semanticscholar.org/paper/fdbcbe71eb418954999c2c2b14014cf49bc2b4ef

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In Behavioral Neuroscience

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In Biological Psychiatry

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Citations in the corpus

• Neuroinflammation and depression: A review (2020, background): “KYN can also be metabolized via a “neuroprotective pathway” to kynurenic acid (KYNA) by the enzyme kynurenine–amino-transferase, which is mainly expressed by astrocytes (Schwarcz et al., 2012).”
• Kynurenine pathway metabolism and the microbiota‐gut‐brain axis (2017, background): “This includes depression and anxiety, as well as cognitive performance, social behaviours and visceral pain perception (McKernan et al., 2010; Moloney et al., 2016; Muller et al., 2015; Nestler et al., 2002; O’Mahony et al., 2014; Schwarcz et al., 2012).”
• Minireview: Gut microbiota: the neglected endocrine organ. (2014, background): “The mechanism underpinning the regulation of circulating tryptophan concentrations by the bacteria in our gut is unclear but may involve control over degradation of tryptophan along an alternative and physiologically dominant metabolic route, the kynurenine pathway (137, 138).”
• Transferring the blues: Depression-associated gut microbiota induces neurobehavioural changes in the rat. (2016, background): “Together with the potential impact on serotonin, increased microbiotamediated degradation of tryptophan along this pathway has a broad range of implications for multiple neurotransmitter systems (Schwarcz et al., 2012).”
• Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease. (2018, neutral): “In this context, IDO1 activation in the periphery, notably in the case of inflammation, may remotely impact these cerebral processes, although the mechanisms involved remain unclear (Schwarcz et al., 2012).”
• Metabolic Interactions in the Tumor Microenvironment (2017, background): “vasoconstriction [29], tryptophan-kynurenine metabolism in the brain and immune system [30], and the glucose-alanine cycle between muscle and liver [31].”