Laboratorio de Aminoácidos Excitadores, Instituto Nacional de Neurología y Neurocirugía, Insurgentes Sur 3877, Mexico City 14269, Mexico.
Neurotoxicology. 2013 Jan;34:189-204. doi: 10.1016/j.neuro.2012.11.007. Epub 2012 Dec 3.
Kynurenine pathway is gaining attention due to the many metabolic processes in which it has been involved. The tryptophan conversion into several other metabolites through this pathway provides neuronal and redox modulators useful for maintenance of major functions in the brain. However, when physiopathological conditions prevail - i.e. oxidative stress, excitotoxicity, and inflammation - preferential formation and accumulation of toxic metabolites could trigger factors for degeneration in neurological disorders. 3-Hydroxykynurenine has been largely described as one of these toxic metabolites capable of inducing oxidative damage and cell death; consequently, this metabolite has been hypothesized to play a pivotal role in different neurological and psychiatric disorders. Supporting evidence has shown altered 3-hydroxykynurenine levels in samples of patients from several disorders. In contrast, some experimental studies have provided evidence of antioxidant and scavenging properties inherent to this molecule. In this review, we explored most of literature favoring one or the other concept, in order to provide an accurate vision on the real participation of this tryptophan metabolite in both experimental paradigms and human brain pathologies. Through this collected evidence, we provide an integrative hypothesis on how 3-hydroxykynurenine is exerting its dual actions in the central nervous system and what will be the course of investigations in this field for the next years.
犬尿氨酸途径由于其参与的许多代谢过程而受到关注。色氨酸通过该途径转化为几种其他代谢物，为大脑的主要功能提供了神经和氧化还原调节剂。然而，当生理病理条件占主导地位时——即氧化应激、兴奋毒性和炎症——优先形成和积累有毒代谢物可能会引发神经退行性疾病中的退化因素。3-羟基犬尿氨酸已被广泛描述为一种能够诱导氧化损伤和细胞死亡的有毒代谢物；因此，该代谢物被假设在不同的神经和精神疾病中发挥关键作用。支持性证据表明，几种疾病患者样本中的 3-羟基犬尿氨酸水平发生了改变。相比之下，一些实验研究提供了证据证明该分子具有内在的抗氧化和清除特性。在这篇综述中，我们探讨了大多数支持其中一个或另一个概念的文献，以便对这种色氨酸代谢物在实验范式和人类大脑病理学中的实际参与提供准确的认识。通过这些收集到的证据，我们提出了一个综合假说，说明 3-羟基犬尿氨酸如何在中枢神经系统中发挥其双重作用，以及在未来几年该领域的研究将如何进行。
