METHODS FOR KYNURENINE SYSTEM IN HUNTINGTON'S DISEASE

原型多电极液相色谱（n-ELC）系统具有 开发用于同时分析数百种成分， 毫微微克级别的生物样本。 n-ELC的主要市场 系统取决于多组分相关性的演示 退行性神经系统疾病的测量。 最近，喹啉 酸（QA）已被证明可以复制组织学和神经化学 亨廷顿病（HD）是一种进行性退行性疾病， 神经紊乱 我们建议开发和应用n-ELC方法， 导致QA的犬尿氨酸（KY）途径的分析。 目的是 开发能够定位HD中代谢缺陷的程序， 增加QA的积累。 同时，n-ELC程序将 提供关于酪氨酸的大约40种其他组分的信息 和色氨酸途径。 这些数据将用于鉴定KY途径 并改善HD和正常人之间的类间相关性。 的 将对来自马萨诸塞州General的CSF进行测量 Hospital，Boston，MA（MGH）和来自姆克林Hospital Brain的脑组织 组织资源中心，贝尔蒙特，MA。 作为MGH正在进行的项目的一部分， 还将分析样品的QA、氨基酸和神经肽。 该项目的长期目标是确定神经化学途径 在HD中，足够详细地指导药理学干预。

Prototype Multiple Electrode Liquid Chromatogrampy (n-ELC) systems have been developed for simultaneous analysis of several hundred components in biological samples at the femtogram level. A major market for n-ELC systems depends on the demonstration of the relevance of multicomponent measurements to degenerative neurological disorders. Recently, quinolinic acid (QA) has been shown to replicate the histological and neurochemical features of Huntington's Disease (HD), a progressive degenerative neurological disorder. We propose to develop and apply n-ELC methods for the analysis of the kynurenine (KY) pathway leading to QA. The intent is to develop procedures capable of locating a metabolic defect in HD leading to increased QA accumulation. Simultaneously, the n-ELC procedures will provide information on approximately 40 other components of the tyrosine and tryptophan pathways. These data will be used to qualify the KY pathway and improve interclass correlations between HD and normals. The measurements will be carried out on CSF from Massachusetts General Hospital, Boston, MA (MGH) and brain tissue from the McLean Hospital Brain Tissue Resource Center, Belmont, MA. As part of an ongoing program at MGH, the samples will also be assayed for QA, amino acids and neuropeptides. The long-range aim of the project is to define the neurochemical pathways in HD in sufficient detail to guide pharmacological intervention.