Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Insurgentes Sur 3877, S.S.A., 14269 México, DF, Mexico.
Oxid Med Cell Longev. 2013;2013:104024. doi: 10.1155/2013/104024. Epub 2013 Sep 5.
Quinolinic acid (QUIN), a neuroactive metabolite of the kynurenine pathway, is normally presented in nanomolar concentrations in human brain and cerebrospinal fluid (CSF) and is often implicated in the pathogenesis of a variety of human neurological diseases. QUIN is an agonist of N-methyl-D-aspartate (NMDA) receptor, and it has a high in vivo potency as an excitotoxin. In fact, although QUIN has an uptake system, its neuronal degradation enzyme is rapidly saturated, and the rest of extracellular QUIN can continue stimulating the NMDA receptor. However, its toxicity cannot be fully explained by its activation of NMDA receptors it is likely that additional mechanisms may also be involved. In this review we describe some of the most relevant targets of QUIN neurotoxicity which involves presynaptic receptors, energetic dysfunction, oxidative stress, transcription factors, cytoskeletal disruption, behavior alterations, and cell death.
喹啉酸(QUIN)是犬尿氨酸途径的一种神经活性代谢物,正常情况下以纳摩尔浓度存在于人脑和脑脊液(CSF)中,常与多种人类神经疾病的发病机制有关。QUIN 是 N-甲基-D-天冬氨酸(NMDA)受体的激动剂,具有很高的体内兴奋毒性。事实上,尽管 QUIN 有摄取系统,但它的神经元降解酶很快就会饱和,细胞外剩余的 QUIN 可以继续刺激 NMDA 受体。然而,它的毒性不能仅仅通过其激活 NMDA 受体来解释,可能还涉及其他机制。在这篇综述中,我们描述了 QUIN 神经毒性的一些最相关的靶点,这些靶点涉及到突触前受体、能量功能障碍、氧化应激、转录因子、细胞骨架破坏、行为改变和细胞死亡。