BRAIN QUINOLINIC ACID METABOLISM--ROLE IN NEUROPATHOLOGY

喹啉酸(Quin)是色氨酸的兴奋性毒性代谢物 通过犬尿氨酸途径代谢。奎宁激活N-甲基-D-天冬氨酸 兴奋性氨基酸受体，可引起惊厥和 神经退行性变。这些影响会被相关的代谢物减弱。 犬尿酸(KYNA)。吲哚-2，3-双加氧酶(IDO)活性， 肝外组织中犬尿氨酸途径的第一个酶是 在免疫系统激活期间增加。因此，Quin和KYNA 可能导致神经元功能障碍和神经退行性变 某些传染病。大量增加的空气中的 Quin和KYNA存在于脑脊液(CSF)中 获得性免疫缺陷综合征(艾滋病)以及其他传染性疾病 猕猴和人类的疾病，尤其是与 神经学和神经病理改变。大脑Quin水平升高 在缺血和胰岛素诱导的低血糖之后。我们的未来 研究的重点是Quin和KYNA的增长是否有 神经致病在传染病中的作用以及是否采取策略 减轻其增加的幅度是有临床好处的。

Quinolinic acid (QUIN) is an excitotoxic metabolite of tryptophan metabolized via the kynurenine pathway. QUIN activates N-methyl-D-aspartate excitatory amino acid receptors and can cause convulsions and neurodegeneration. These effects are attenuated by the related metabolite kynurenic acid (KYNA). The activity of indoleamine-2,3 dioxygenase (IDO), the first enzyme of the kynurenine pathway in extrahepatic tissues, is increased during activation of the immune system. Therefore, QUIN and KYNA may contribute to neuronal dysfunction and neurodegeneration that accompany certain infectious diseases. Substantial increases in the concentrations of QUIN and KYNA occur in the cerebrospinal fluid (CSF) of patients with the acquired immune deficiency syndrome (AIDS) as well as other infectious disease in macaques and humans, particularly diseases associated with neurologic and neuropathologic changes. Brain QUIN levels are increased following both ischemia and insulin-induced hypoglycemia. Our future studies are focused on whether the increases in QUIN and KYNA have a neuropathogenic role in infectious diseases and whether strategies to attenuate the magnitude of their increase are of clinical benefit.