CSIR - Centre for Cellular and Molecular Biology (CCMB), Hyderabad, India.
Proteomics facility, CSIR - Centre for Cellular and Molecular Biology (CCMB), Hyderabad, India.
Proteomics. 2016 May;16(9):1407-20. doi: 10.1002/pmic.201500291.
Parkinson's disease (PD) is the most common age associated neurodegenerative disease, which has been extensively studied for its etiology and phenotype. PD has been widely studied in alternate model system such as rodents towards understanding the role of neurotoxin by inducing PD. This study is aimed to understand the biomechanism of PD in zebrafish model system induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The phenotype and role of various genes and proteins for Parkinsonism were tested and evaluated in this study using behavior, molecular and proteomic approaches. Zebrafish PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine showed a significant level of decrease in the movement with erratic swimming pattern and increased freezing bouts. CHCHD2, EEF2B, LRRK2, PARK7, PARK2, POLG, SNCGB and SYNB genes were differentially regulated at the transcript level in PD zebrafish. Similarly a total of 73 proteins were recognized as differentially expressed in the nervous system of zebrafish due to Parkinsonism based on quantitative proteomics approach. Proteins such as NEFL, MUNC13-1, NAV2 and GAPVD1 were down regulated in the zebrafish brain for the PD phenotype, which were associated with the neurological pathways. This zebrafish based PD model can be used as a potential model system for screening prospective drug molecules for PD.
帕金森病(PD)是最常见的与年龄相关的神经退行性疾病,其病因和表型已得到广泛研究。为了了解神经毒素的作用,已经在啮齿动物等替代模型系统中广泛研究了 PD。本研究旨在了解 1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的斑马鱼模型系统中 PD 的生物力学机制。本研究采用行为学、分子和蛋白质组学方法,测试和评估了各种与帕金森病相关的基因和蛋白质的表型和作用。MPTP 诱导的斑马鱼 PD 模型运动能力显著下降,表现为不规则游泳模式和冻结发作增加。CHCHD2、EEF2B、LRRK2、PARK7、PARK2、POLG、SNCGB 和 SYNB 基因在 PD 斑马鱼的转录水平上差异调节。同样,基于定量蛋白质组学方法,共识别出 73 种蛋白质在帕金森病斑马鱼的神经系统中差异表达。神经纤维蛋白(NEFL)、MUNC13-1、NAV2 和 GAPVD1 等蛋白在 PD 表型的斑马鱼脑中下调,这些蛋白与神经通路有关。这种基于斑马鱼的 PD 模型可作为筛选 PD 潜在药物分子的潜在模型系统。