Kynurenine (Kyn) pathway is a significant metabolic pathway of tryptophan (Trp). The metabolites of the Kyn pathway are closely correlated with numerous diseases. Two main enzymes, indoleamine-2,3-dioxygenase (IDO) and tryptophan-2,3-dioxygenase (TDO or TDO2), regulate the first and rate-limiting step of the Kyn pathway. These enzymes are directly or indirectly involved in various diseases, including inflammatory diseases, cancer, diabetes, and mental disorders. Presently, an increasing number of potential mechanisms have been revealed. In the present review, we depict the structure of IDO and TDO and explicate their functions in various diseases to facilitate a better understanding of them and to indicate new therapeutic plans to target them. Moreover, we summarize the inhibitors of IDO/TDO that are currently under development and their efficacy in the treatment of cancer and other diseases.
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http://dx.doi.org/10.7150/jca.31727 | DOI Listing |
Front Biosci (Landmark Ed)
January 2025
HUN-REN-SZTE Neuroscience Research Group, Hungarian Research Network, University of Szeged (HUN-REN-SZTE), Danube Neuroscience Research Laboratory, H-6725 Szeged, Hungary.
Backgrounds: Memory and emotion are especially vulnerable to psychiatric disorders such as post-traumatic stress disorder (PTSD), which is linked to disruptions in serotonin (5-HT) metabolism. Over 90% of the 5-HT precursor tryptophan (Trp) is metabolized via the Trp-kynurenine (KYN) metabolic pathway, which generates a variety of bioactive molecules. Dysregulation of KYN metabolism, particularly low levels of kynurenic acid (KYNA), appears to be linked to neuropsychiatric disorders.
View Article and Find Full Text PDFBiomolecules
January 2025
Department of Radiology, Nemours Children's Health, Delaware, Wilmington, DE 19803, USA.
Tryptophan (Trp)-based radiotracers have excellent potential for imaging many different types of brain pathology because of their involvement with both the serotonergic and kynurenine (KYN) pathways. However, radiotracers specific to the kynurenine metabolism pathway are limited. In addition, historically Trp-based radiopharmaceuticals were synthesized with the short-lived isotope carbon-11.
View Article and Find Full Text PDFJ Physiol Investig
January 2025
Department and Institute of Physiology, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that regulates cell immune responses in a cell type-specific and ligand-dependent manner. In the central nervous system, astrocytic AhR plays important roles in regulating neuroinflammation by mediating responses to endogenous ligands generated from the inflammation-induced indoleamine 2,3-dioxygenase 1 (IDO1)/kynurenine (KYN) pathway. We previously demonstrated that reduction of AhR expression decreases lipopolysaccharide (LPS)-induced pro-inflammatory responses in microglia.
View Article and Find Full Text PDFJ Transl Med
January 2025
Department of Hematology, Tianjin First Central Hospital, Tianjin, China.
Chimeric antigen receptor (CAR) T-cell therapy plays a critical role in the treatment of B-cell hematologic malignancies. The combination of PD-1 inhibitors and CAR-T has shown encouraging results in treating patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). However, there are still cases where treatment is ineffective.
View Article and Find Full Text PDFSci Rep
January 2025
Affiliated Mental Health Centre & Hangzhou Seventh People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310013, China.
The tryptophan (TRP)-kynurenine (KYN) pathway is involved in the pathogenesis of schizophrenia. This study aimed to investigate the levels of TRP-KYN metabolites in serum and urine of patients with first-episode schizophrenia (FES) and their association with clinical manifestations. This study included 38 drug-naive patients with FES and 43 healthy controls (HCs).
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