Kynurenine pathway metabolism and neuroinflammatory disease.
Kynurenine pathway metabolism and neuroinflammatory disease.
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DOI：
10.4103/1673-5374.198971
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发表时间：
2017-01
影响因子：
6.1
通讯作者：
Grant R
中科院分区：
文献类型：
--
作者：
Braidy N;Grant R
免疫介导的激活色氨酸（TRYP）分解代谢通过犬尿氨酸途径（KP）是一个一致的发现在所有炎性疾病。本小组和其他研究人员进行了几项研究，研究了神经反应性TRYP代谢物的神经毒性潜力，包括喹啉酸（QUIN）在神经炎性神经疾病中的作用，包括阿尔茨海默病（AD）、多发性硬化症、肌萎缩性侧索硬化症（ALS）和艾滋病相关痴呆复合体（ADC）。我们目前的工作旨在确定在免疫反应期间通过KP增强TRYP的分解代谢是否对受影响的个体有任何益处。在生理条件下，QUIN被代谢为必需的吡啶核苷酸，烟酰胺腺嘌呤二核苷酸（NAD+），是一种重要的代谢辅助因子和电子转运体。NAD+还作为DNA“缺口传感器”和假定的核修复酶，聚（adp -核糖）聚合酶（PARP）的底物。自由基引发的DNA损伤、PARP激活和NAD+耗竭可能导致神经炎性疾病的脑功能障碍和细胞死亡。
Immune-mediated activation of tryptophan (TRYP) catabolism via the kynurenine pathway (KP) is a consistent finding in all inflammatory disorders. Several studies by our group and others have examined the neurotoxic potential of neuroreactive TRYP metabolites, including quinolinic acid (QUIN) in neuroinflammatory neurological disorders, including Alzheimer's disease (AD), multiple sclerosis, amylotropic lateral sclerosis (ALS), and AIDS related dementia complex (ADC). Our current work aims to determine whether there is any benefit to the affected individuals in enhancing the catabolism of TRYP via the KP during an immune response. Under physiological conditions, QUIN is metabolized to the essential pyridine nucleotide, nicotinamide adenine dinucleotide (NAD+), which represents an important metabolic cofactor and electron transporter. NAD+ also serves as a substrate for the DNA ‘nick sensor’ and putative nuclear repair enzyme, poly(ADP-ribose) polymerase (PARP). Free radical initiated DNA damage, PARP activation and NAD+ depletion may contribute to brain dysfunction and cell death in neuroinflammatory disease.