Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, Beijing, P. R. China.
Proteomics Clin Appl. 2007 Dec;1(12):1559-69. doi: 10.1002/prca.200700077. Epub 2007 Nov 16.
The dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) replicates many of the pathological hallmarks of Parkinson's disease (PD) in mice via selective destruction of dopamine neurons of the substantia nigra and striatum. Although MPTP has been widely used to study downstream effects following the degeneration of dopaminergic neurons, the underlying mechanisms of MPTP action remain poorly understood. To determine the underlying mechanisms of MPTP action at the protein level, a 2-DE-based proteomics approach was used to evaluate the changes in protein expression in substantia nigra and striatal tissue in C57BL/6 mice after MPTP administration. We identified nine proteins that were markedly altered and are likely to be involved in mitochondrial function, heat shock protein activity, and which contribute enzyme activities for energy metabolism and protein degradation.
多巴胺能神经毒素 1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)通过选择性破坏黑质和纹状体中的多巴胺神经元,在小鼠中复制了帕金森病(PD)的许多病理特征。尽管 MPTP 已被广泛用于研究多巴胺能神经元退化后的下游效应,但 MPTP 作用的潜在机制仍知之甚少。为了确定 MPTP 在蛋白质水平上的作用机制,采用基于 2-DE 的蛋白质组学方法来评估 C57BL/6 小鼠给予 MPTP 后黑质和纹状体组织中蛋白质表达的变化。我们鉴定了 9 种明显改变的蛋白质,它们可能参与线粒体功能、热休克蛋白活性,并为能量代谢和蛋白质降解提供酶活性。