Tryptophan Metabolism Through the Kynurenine Pathway in Glial Cells
Deivison Silva Argolo,
Lucas Matheus Gonçalves de Oliveira,
Gilles J. Guillemin,
George E. Barreto,
Arthur Morgan Butt,
Silvia Lima Costa,
Maria de Fátima Dias Costa
Affiliations
Deivison Silva Argolo
Laboratory of Neurochemistry and Cellular Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Av. Reitor Miguel Calmon S/N, Salvador 40231-300, Brazil
Lucas Matheus Gonçalves de Oliveira
Laboratory of Neurochemistry and Cellular Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Av. Reitor Miguel Calmon S/N, Salvador 40231-300, Brazil
Gilles J. Guillemin
Department of Chemistry, Faculty of Mathematics and Natural Sciences, IPB University, Bogor 16680, Indonesia
George E. Barreto
Neuroendocrine Pharmacology Laboratory, Department of Biological Sciences, Faculty of Science and Engineering, University of Limerick, V94 T9PX Limerick, Ireland
Arthur Morgan Butt
School of Medicine, Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth PO1 2UP, UK
Silvia Lima Costa
Laboratory of Neurochemistry and Cellular Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Av. Reitor Miguel Calmon S/N, Salvador 40231-300, Brazil
Maria de Fátima Dias Costa
Laboratory of Neurochemistry and Cellular Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Av. Reitor Miguel Calmon S/N, Salvador 40231-300, Brazil
The central nervous system (CNS) relies on complex and dynamic interactions between neurons and glial cells. Among glial cells, astrocytes regulate the chemical environment surrounding neurons and supply essential nutrients for brain metabolism whereas microglia, the resident macrophages of the CNS, play critical roles in homeostasis, defense, and responses to injury. Both microglia and astrocytes contribute to the regulation of excitotoxicity and inflammation mediated by the metabolism of tryptophan (Trp) via the kynurenine pathway. Trp metabolism generates several bioactive metabolites, including quinolinic acid (QUIN) and kynurenic acid (KYNA), which have opposing effects. QUIN, produced by activated microglia, acts as an agonist for NMDA receptors; excessive stimulation of these receptors can lead to excitotoxicity and neuronal death. Conversely, KYNA, primarily produced by astrocytes via kynurenine 2,3-aminotransferases (KAT), acts as an NMDA receptor antagonist, conferring neuroprotection by mitigating excitotoxicity. Dysregulation of the Trp metabolism is implicated in many neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis and amyotrophic lateral sclerosis, as well as in various neuropsychiatric disorders. This review examines the cellular and molecular mechanisms underlying Trp metabolism in glial cells, highlighting the unique contributions of each glial phenotype, the implications for CNS pathologies, and the potential biomarkers and therapeutic targets for restoring homeostasis and preventing disease progression.
