REVIEW ARTICLESThe ‘Yin’ and the ‘Yang’ of the kynurenine pathway: excitotoxicity and neuroprotection imbalance in stress-induced disordersBarone, PascalAuthor Information UMR 1253, iBrain, University of Tours, Inserm, Tours, France Correspondence to Pascal Barone, PhD, UMR 1253, iBrain, Faculty of Sciences, Université de Tours, Inserm, Parc Grandmont, Tours 37200, France E-mail: email@example.com Behavioural Pharmacology: April 2019 - Volume 30 - Issue 2 and 3 - p 163-186 doi: 10.1097/FBP.0000000000000477 Buy Metrics Abstract The amino-acid tryptophan (TRY) is converted into kynurenine (KYN) and subsequent metabolites by the tryptophan/catabolites (TRY/CAT) pathway (kynurenine pathway). ‘Excito-toxic’ and ‘neuro-protective’ metabolites are produced, which modulate the glutamatergic neurotransmission. The TRY/CAT pathway is activated by hypothalamic–pituitary–adrenal endocrine induction during stress by corticoids hormones, and the excitotoxic branch of the TRY/CAT pathway is activated by proinflammatory cytokines. During stress and major depressive disorders, it is generally accepted that inflammation induces an imbalance toward the excitotoxic branch of the TRY/CAT pathway, causing changes in brain connectivity in corticolimbic structures and therefore psychocognitive abnormalities. In neurodegenerative diseases, the activation of the oxidative branch of the TRY/CAT pathway has been frequently reported. We propose a comprehensive survey of the TRY/CAT pathway (kynurenine pathway) abnormalities in stress and inflammation-induced MDD and neurodegenerative diseases. As TRY/CAT pathway is a common feature of stress, inflammation, affective disorders, and neurodegenerative diseases, we discuss the status of the TRY/CAT pathway as a possible link among chronic stress, inflammation, depressive disorders and neurodegenerative diseases. This review does not claim to be exhaustive, but in a pharmacological perspective, it will be proposed that modulation of the excitotoxicity/neuroprotection balance is a valuable strategy for new and more effective treatments of mood disorders. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.