Journal
EXPERT OPINION ON THERAPEUTIC TARGETS
Volume 13, Issue 2, Pages 247-258Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1517/14728220802665734
Keywords
3HAD; Huntington's disease; IDO; immunoediting; KNT; kynurenine pathway; kynurenines; schizophrenia; tryptophan
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Funding
- University of Parma [FIL2007]
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Background: The kynurenine pathway (KP), the primary route of tryptophan degradation in mammalian cells, consists of a cascade of enzymatic reactions eventually leading to NAD+ formation. Many metabolites along the route have biological activities, especially in the nervous and immune systems. Objective/methods: This review focuses on three therapeutic areas, tumor immunoediting, schizophrenia, and Huntington's disease, apparently disconnected but linked by preliminary proof-of-concept of KP involvement. The potential embedded in drug discovery programs aimed at the identification of selective inhibitors with optimized pharmacodynamic and pharmacokinetic properties for human studies is discussed. Results/conclusions: Recent advances have shifted the attention on the kynurenine pathway from a scientific curiosity to a clinically relevant collection of targets. A relatively large number of ligands able to interfere with individual enzymes of the pathway have been made available, but none have so far proceeded into advanced clinical studies.
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