Journal ArticleDOI
Endogenous kynurenines as targets for drug discovery and development
Trevor W. Stone,L. G. Darlington +1 more
TLDR
The kynurenine pathway is the main pathway for tryptophan metabolism and generates compounds that can modulate activity at glutamate receptors and possibly nicotinic receptors, in addition to some as-yet-unidentified sites.Abstract:
At-a-glance The kynurenine pathway is the main pathway for tryptophan metabolism. It generates compounds that can modulate activity at glutamate receptors and possibly nicotinic receptors, in addition to some as-yet-unidentified sites. The pathway is in a unique position to regulate other aspects of the metabolism of tryptophan to neuroactive compounds, and also seems to be a key factor in the communication between the nervous and immune systems. It also has potentially important roles in the regulation of cell proliferation and tissue function in the periphery. As a result, the pathway presents a multitude of potential sites for drug discovery in neuroscience, oncology and visceral pathology.read more
Citations
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IDO expression by dendritic cells: tolerance and tryptophan catabolism.
Andrew L. Mellor,David H. Munn +1 more
TL;DR: This review summarizes key recent developments and proposes a unifying model for the role of IDO in tolerance induction, including studies of mammalian pregnancy, tumour resistance, chronic infections and autoimmune diseases.
Journal ArticleDOI
An Interaction between Kynurenine and the Aryl Hydrocarbon Receptor Can Generate Regulatory T Cells
Joshua D. Mezrich,John H. Fechner,Xiaoji Zhang,Brian P. Johnson,William J. Burlingham,Christopher A. Bradfield +5 more
TL;DR: It is demonstrated that kynurenine, the first breakdown product in the IDO-dependent tryptophan degradation pathway, activates the aryl hydrocarbon receptor and this activation leads to AHR-dependent Treg generation, which shed light on the relationship of IDO to the generation of Tregs.
Journal ArticleDOI
Cytokines and major depression.
TL;DR: Although the central effects of proinflammatory cytokines appear to be able to account for most of the symptoms occurring in depression, it remains to be established whether cytokines play a causal role in depressive illness or represent epiphenomena without major significance.
Journal ArticleDOI
NAD(+) Metabolism and the Control of Energy Homeostasis: A Balancing Act between Mitochondria and the Nucleus.
TL;DR: This review summarizes how NAD(+) metabolism links energy status with adaptive cellular and organismal responses and how this knowledge can be therapeutically exploited.
Journal ArticleDOI
Indoleamine 2,3-dioxygenase and tumor-induced tolerance.
David H. Munn,Andrew L. Mellor +1 more
TL;DR: Strategies to block Indoleamine 2,3-dioxygenase (IDO) might enhance the effectiveness of tumor immunotherapy.
References
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Journal ArticleDOI
Prevention of allogeneic fetal rejection by tryptophan catabolism
David H. Munn,Min Zhou,John T. Attwood,Igor Bondarev,Simon J. Conway,Brendan Marshall,Corrie C. Brown,Andrew L. Mellor +7 more
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Replication of the neurochemical characteristics of Huntington's disease by quinolinic acid
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Journal ArticleDOI
Quinolinic acid: an endogenous metabolite that produces axon-sparing lesions in rat brain
TL;DR: Intracerebral injection of the neuroexcitatory tryptophan metabolite, quinolinic acid, has behavioral, neurochemical and neuropathological consequences reminiscent of those of exogenous excitotoxins, such as kainic and ibotenic acids.
Journal Article
Neuropharmacology of quinolinic and kynurenic acids.
TL;DR: Whatever the specific nature of their physiological roles, the presence of an endogenous selective agonist and antagonist acting at NMDA receptors must continue to present exciting possibilities for understanding the pathological basis of several CNS disorders as well as developing new therapeutic approaches.
Journal ArticleDOI
Interferon gamma blocks the growth of Toxoplasma gondii in human fibroblasts by inducing the host cells to degrade tryptophan.
TL;DR: Several hypotheses are presented to explain how the intracellular degradation of tryptophan induced by gamma interferon could restrict the growth of an obligate intrACEllular parasite.
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