Mandel Silvia A, Fishman Tali, Youdim Moussa B H
Eve Topf Center for Neurodegenerative Diseases Research and Department of Pharmacology, Faculty of Medicine, Technion, Haifa, Israel.
Parkinsonism Relat Disord. 2007;13 Suppl 3:S242-7. doi: 10.1016/S1353-8020(08)70009-9.
High-throughput gene-based platform studies in human post-mortem substantia nigra from sporadic Parkinson's disease (PD) cases have revealed significant dysregulation of genes involved in biological processes linked to previously established neurodegenerative mechanisms both in sporadic and hereditary PD. These include protein aggregation, mitochondrial dysfunction, oxidative stress, cell cycle, vesicle trafficking, synaptic transmission, dopamine metabolism and cell adhesion/cytoskeleton maintenance. These observations have extended our current view on the molecular pathways underlying the etio-pathology of the disease and provided a basis for the development of a novel genetic model of sporadic PD, centered on gradual silencing/over-expression of the candidate genes. The uncovered signatures may serve as future predictive biomarkers for early PD diagnosis, disease progression and drug development.
对散发性帕金森病（PD）患者死后黑质进行的基于高通量基因的平台研究表明，在散发性和遗传性PD中，参与与先前确立的神经退行性机制相关的生物学过程的基因存在显著失调。这些过程包括蛋白质聚集、线粒体功能障碍、氧化应激、细胞周期、囊泡运输、突触传递、多巴胺代谢以及细胞黏附/细胞骨架维持。这些观察结果扩展了我们目前对该疾病病因病理学潜在分子途径的认识，并为开发一种以候选基因的逐渐沉默/过表达为核心的散发性PD新遗传模型提供了基础。所发现的特征可能作为未来早期PD诊断、疾病进展和药物开发的预测性生物标志物。
