Queen Mary, University of London, London, E1 4NS, UK.
Cell Death Differ. 2010 Jul;17(7):1115-25. doi: 10.1038/cdd.2009.217. Epub 2010 Jan 22.
As evidence emerges that complex gene alterations are involved in the onset of Parkinson's disease (PD), the role of environmental chemicals in the pathogenesis of this disease becomes intensely debated. Although it is undisputed that acute exposure to certain chemicals such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is sufficient to cause human parkinsonism, the evidence that the risk for PD increases because of environmental exposure is generally weaker. Several studies have suggested that pesticide exposure and life in rural areas are significant risks factors for PD. Among other pesticides, paraquat (PQ) has been linked to PD by epidemiological studies and experimental work in rodents, in which it causes lesions in the substantia nigra, pars compacta. However, the evidence that human exposure to the chemical results in an increased risk for PD is rather limited and based on insufficient epidemiological data. This review critically analyses the evidence that implicates PQ in parkinsonism and discusses the limitations of chemical modelling of PD.
随着越来越多的证据表明复杂的基因改变与帕金森病(PD)的发病有关,环境化学物质在该病发病机制中的作用成为激烈争论的焦点。虽然毫无争议的是,急性暴露于某些化学物质,如 1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)足以导致人类帕金森病,但由于环境暴露而导致 PD 风险增加的证据通常较弱。一些研究表明,农药暴露和农村生活是 PD 的重要危险因素。在其他农药中,百草枯(PQ)已通过流行病学研究和啮齿动物实验工作与 PD 相关联,其中它会导致黑质致密部的损伤。然而,人类接触这种化学物质会增加 PD 风险的证据相当有限,并且基于不充分的流行病学数据。这篇综述批判性地分析了 PQ 与帕金森病相关的证据,并讨论了 PD 化学模型的局限性。