Institute for Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
FEBS J. 2012 Apr;279(8):1386-97. doi: 10.1111/j.1742-4658.2012.08487.x. Epub 2012 Mar 27.
The oxidative pathway for the metabolism of tryptophan along the kynurenine pathway generates quinolinic acid, an agonist at N-methyl-D-aspartate receptors, as well as kynurenic acid which is an antagonist at glutamate and nicotinic receptors. The pathway has become recognized as a key player in the mechanisms of neuronal damage and neurodegenerative disorders. As a result, manipulation of the pathway, so that the balance between the levels of components of the pathway can be modified, has become an attractive target for the development of pharmacological agents with the potential to treat those disorders. This review summarizes some of the relevant background information on the pathway itself before identifying some of the chemical strategies for its modification, with examples of their successful application in animal models of infection, stroke, traumatic brain damage, cerebral malaria and cerebral trypanosomiasis.
色氨酸代谢沿犬尿氨酸途径的氧化途径产生喹啉酸，一种 N-甲基-D-天冬氨酸受体的激动剂，以及犬尿氨酸酸，一种谷氨酸和烟碱受体的拮抗剂。该途径已被认为是神经元损伤和神经退行性疾病机制中的关键因素。因此，操纵该途径，使途径成分的水平之间的平衡可以被修饰，已成为开发具有治疗这些疾病潜力的药理制剂的有吸引力的目标。本综述总结了该途径本身的一些相关背景信息，然后确定了一些用于修饰该途径的化学策略，并举例说明了它们在感染、中风、创伤性脑损伤、脑疟疾和脑锥虫病的动物模型中的成功应用。
