Elemental Bio-imaging Facility, University of Technology Sydney, New South Wales, Australia.
Metallomics. 2013 Feb;5(2):91-109. doi: 10.1039/c2mt20164j.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a potent toxin used to selectively destroy dopaminergic neurons in the substantia nigra and induce parkinsonism. MPTP is metabolised to the 1-methyl-4-phenylpyridinium ion (MPP(+)) in glia, after which it enters the neuron via the dopamine transporter and results in elevated levels of oxidative stress. The mechanism through which MPP(+) causes cell death is thought to involve redox-active metals, particularly iron (Fe). This review will examine how cellular metal metabolism is altered following MPTP insult, and how this relates to metal dyshomeostasis in idiopathic Parkinson's disease. This includes both cell damage arising from increased metal concentration, and how metal-binding proteins respond to MPTP-induced neurotoxicity. Implications for using MPTP as a model for human Parkinson's disease will be discussed in terms of cell metallobiology.
1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）是一种有效的毒素，可用于选择性地破坏黑质中的多巴胺能神经元并诱发帕金森病。MPTP 在神经胶质细胞中代谢为 1-甲基-4-苯基吡啶鎓离子（MPP(+)），然后通过多巴胺转运蛋白进入神经元，导致氧化应激水平升高。MPP(+) 导致细胞死亡的机制被认为涉及氧化还原活性金属，特别是铁（Fe）。本综述将探讨 MPTP 损伤后细胞金属代谢如何发生改变，以及这与特发性帕金森病中的金属动态失衡有何关系。这包括由于金属浓度增加而引起的细胞损伤，以及金属结合蛋白如何应对 MPTP 诱导的神经毒性。将从细胞金属生物学的角度讨论使用 MPTP 作为人类帕金森病模型的意义。
