Tryptophan Metabolism as a Pharmacological Target. (January 2021)

• Record Type: Journal Article
• Authors: Modoux, Morgane; Rolhion, Nathalie; Mani, Sridhar; Sokol, Harry
• Is Part Of: Trends in pharmacological sciences. Volume 42:Number 1(2021)
• Page Start: 60
• Page End: 73
• Publication Date: 2021-01
• Subjects: tryptophan -- kynurenine, serotonin -- IDO -- AhR -- therapeutics; Pharmacology -- Periodicals; Pharmacology -- trends -- Periodicals; Pharmacologie -- Périodiques; Pharmacology; Electronic journals; Periodicals; 615.1
• DOI: 10.1016/j.tips.2020.11.006
• Languages: English
• ISSNs: 0165-6147

Abstract

Abstract : L-Tryptophan is an essential amino acid required for protein synthesis. It undergoes an extensive and complex metabolism along several pathways, resulting in many bioactive molecules acting in various organs through different action mechanisms. Enzymes involved in its metabolism, metabolites themselves, or their receptors, represent potential therapeutic targets, which are the subject of dynamic research. Disruptions in L-tryptophan metabolism are reported in several neurological, metabolic, psychiatric, and intestinal disorders, paving the way to develop drugs to target it. This review will briefly describe L-tryptophan metabolism and present and discuss the most recent pharmacological developments targeting it. Highlights: L-Tryptophan (L-Trp) is metabolized via three pathways: the indole pathway in bacteria and the kynurenine and serotonin pathways in mammalian cells. Disruptions in L-Trp metabolism are reported in several diseases making L-Trp metabolism a promising therapeutic target. Manipulating L-Trp metabolism is an attractive therapeutic strategy. Key enzymes of L-Trp metabolism are targets of inhibitors currently undergoing clinical trials in cancerology, dermatology, and gastroenterology. Serotonin and aryl hydrocarbon receptor (AhR) receptors are targeted in the treatment of gastrointestinal diseases, inflammation, and many cancers. Next-generation probiotics producing indoles are being developed for their ability to activate AhR in the gut.