色氨酸-犬尿氨酸途径是什么，它为何对神经治疗学很重要？
What is the tryptophan kynurenine pathway and why is it important to neurotherapeutics?
作者信息
Davis Ian, Liu Aimin
机构信息
Department of Chemistry, Atlanta, GA 30303, USA.
出版信息
Expert Rev Neurother. 2015;15(7):719-21. doi: 10.1586/14737175.2015.1049999. Epub 2015 May 24.
Abstract
The kynurenine pathway has received increasing attention as its connection to inflammation, the immune system and neurological conditions has become more apparent. It is the primary route for tryptophan catabolism in the liver and the starting point for the synthesis of nicotinamide adenine dinucleotide in mammals. Dysregulation or overactivation of this pathway can lead to immune system activation and accumulation of potentially neurotoxic compounds. These aspects make the kynurenine pathway a promising target for therapeutic development to treat inflammation and disease with neurological aspects, especially in cancer patients undergoing chemotherapy.
摘要
犬尿氨酸途径受到越来越多的关注，因为它与炎症、免疫系统和神经系统疾病的联系变得更加明显。它是肝脏中色氨酸分解代谢的主要途径，也是哺乳动物中烟酰胺腺嘌呤二核苷酸合成的起点。该途径的失调或过度激活会导致免疫系统激活和潜在神经毒性化合物的积累。这些方面使犬尿氨酸途径成为治疗炎症和伴有神经方面疾病的有前景的治疗开发靶点，尤其是在接受化疗的癌症患者中。
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本文引用的文献
1
Crystallographic and spectroscopic snapshots reveal a dehydrogenase in action.
Nat Commun. 2015 Jan 7;6:5935. doi: 10.1038/ncomms6935.
2
Deal watch: Genentech dives deeper into the next wave of cancer immunotherapies.
Nat Rev Drug Discov. 2014 Dec;13(12):879. doi: 10.1038/nrd4502.
3
Human α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD): a structural and mechanistic unveiling.
Proteins. 2015 Jan;83(1):178-87. doi: 10.1002/prot.24722. Epub 2014 Nov 21.
4
Heme-dependent dioxygenases in tryptophan oxidation.
Arch Biochem Biophys. 2014 Feb 15;544:18-26. doi: 10.1016/j.abb.2013.11.009. Epub 2013 Dec 1.
5
Do cytokines really sing the blues?
Cerebrum. 2013 Aug 1;2013:10. eCollection 2013.
6
The power of two: arginine 51 and arginine 239* from a neighboring subunit are essential for catalysis in α-amino-β-carboxymuconate-epsilon-semialdehyde decarboxylase.
J Biol Chem. 2013 Oct 25;288(43):30862-71. doi: 10.1074/jbc.M113.496869. Epub 2013 Sep 9.
7
Conceptual confluence: the kynurenine pathway as a common target for ketamine and the convergence of the inflammation and glutamate hypotheses of depression.
Neuropsychopharmacology. 2013 Aug;38(9):1607-8. doi: 10.1038/npp.2013.140.
8
An expanding range of targets for kynurenine metabolites of tryptophan.
Trends Pharmacol Sci. 2013 Feb;34(2):136-43. doi: 10.1016/j.tips.2012.09.006. Epub 2012 Nov 1.
9
Kynurenines in the mammalian brain: when physiology meets pathology.
Nat Rev Neurosci. 2012 Jul;13(7):465-77. doi: 10.1038/nrn3257.
10
Quinolinic Acid, an endogenous molecule combining excitotoxicity, oxidative stress and other toxic mechanisms.
Int J Tryptophan Res. 2012;5:1-8. doi: 10.4137/IJTR.S8158. Epub 2012 Feb 23.
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