BIOMARKERS FOR PRECLINICAL PARKINSON?S DISEASE

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 帕金森氏病是一种进行性神经退行性疾病，在出现第一个运动症状之前许多年就开始了。因此，如果能够在疾病过程中进行早期干预，减缓或逆转中脑多巴胺能神经元的进行性退化，可能会对疾病的发展产生重大影响。该项目的目标是确定临床前生物标记物，使有风险的患者有机会使用神经保护性治疗药物进行预治疗，这种药物可以显著延缓甚至防止多巴胺能神经元的死亡和运动障碍的发展。该项目与华盛顿大学的张静博士合作，旨在使用蛋白质组学方法从MPTP治疗的猴子的血清、脑脊液和脑组织中识别此类生物标记物。虽然这个项目还没有收集到数据，但总共有10只猴子接受了MPTP治疗，直到它们达到纹状体多巴胺丢失的30%-40%(无症状组)或70%-80%(有症状组)，这是使用多巴胺转运体配体的PET扫描成像所测量的。另一组动物作为对照，被注射了车辆。当他们达到去纹状体多巴胺所需的水平后，在动物被处死之前，进行脊髓敲击和血清提取，脑组织将用于蛋白质组学测量。这些猴子研究的结果将与从高危患者收集的血清和脑脊液测量结果进行比较。总之，这些发现可能为描述生物标记物的特征提供第一个证据，这些生物标记物可以预测人类帕金森氏病的发展。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Parkinson's disease is a progressive neurodegenerative disorder that starts many years prior to the appearance of the first motor symptoms. Thus, if one could intervene early in the disease process to slow down or reverse the progressive degeneration of midbrain dopaminergic neurons, it could have a significant impact on the development of the disease. The goal of this project is to identify preclinical biomarkers that would give the opportunity to pre-treat at risk patients with neuroprotective therapeutic drugs, which could significantly delay or even prevent the death of dopaminergic neurons and the development of motor deficits. In collaboration with Dr Jing Zhang at the University of Washington, this project aims at identifying such biomarkers using proteomics approach from the serum, cerebrospinal fluid and brain tissue in MPTP-treated monkeys. Although no data have yet been collected in this project, a total of 10 monkeys have been treated with MPTP until they reach about 30-40% ("asymptomatic group") or 70-80% ("symptomatic group") striatal dopamine loss, as measured using PET scan imaging for dopamine transporter ligands. Another group of animals, used as controls, was injected with vehicle. After they have reached the required level of striatal dopamine denervation, spinal taps and serum draw were performed before the animals were sacrificed and the brain tissue will be used for proteomics measurements. The results of these monkey studies will be compared with those gathered from serum and CSF measurements collected from at risk patients. Together, these findings could provide the first evidence for the characterization of biomarkers that could predict the development of Parkinson's disease in humans.