Environmental factors in Parkinson's disease
Environmental factors in Parkinson's disease
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DOI：
10.1016/s0161-813x(02)00099-2
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发表时间：
2002-10-01
期刊：
影响因子：
3.4
通讯作者：
Manning-Bog, AB
中科院分区：
文献类型：
--
作者：
Di Monte, DA;Lavasani, M;Manning-Bog, AB
这篇综述文章中讨论的证据有力地支持了环境因素在帕金森氏病中的病因作用。首先，由于mptp(1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine)，的发现，现在很清楚，通过针对黑质纹状体系统，神经毒剂可以重现特发性帕金森症的神经化学和病理特征。MPTP引发的一系列毒性事件也为我们提供了关于毒物选择性和黑质纹状体脆弱性机制的有趣线索。相关的例子是(I)质膜多巴胺转运体在促进潜在有毒物质进入多巴胺能神经元中的作用；(Ii)黑质纹状体系统对线粒体能量代谢失败的脆弱性；以及(Iii)炎症过程对组织损伤的贡献。流行病学和实验数据表明，神经毒剂(如杀虫剂)或神经保护化合物(如烟草制品)等特定物质可能参与黑质纹状体变性的发病，进一步支持环境与帕金森氏病之间的关系。从我们目前的知识中可能出现的一种情况是，神经退化是多种事件和交互机制的结果。这些可能包括(I)内源性和外源性毒素的协同作用(例如杀虫剂二乙基二硫代氨基甲酸酯促进其他化合物毒性的能力)；(Ii)有毒物质与内源性元素(例如蛋白质α-突触核蛋白)的相互作用；(Iii)组织对最初有毒侮辱的反应；以及最后但并非最不重要的是，(Iv)环境因素对遗传倾向和衰老背景的影响。(C)2002 Elsevier Science Inc.保留所有权利。
Evidence discussed in this review article lends strong support in favor of an etiologic role of environmental factors in Parkinson's disease. First, thanks to the discovery of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), it is now clear that, by targeting the nigrostriatal system, neurotoxicants can reproduce the neurochemical and pathological features of idiopathic parkinsonism. The sequence of toxic events triggered by MPTP has also provided us with intriguing clues concerning mechanisms of toxicant selectivity and nigrostriatal vulnerability. Relevant examples are (i) the role of the plasma membrane dopamine transporter in facilitating the access of potentially toxic species into dopaminergic neurons; (ii) the vulnerability of the nigrostriatal system to failure of mitochondrial energy metabolism; and (iii) the contribution of inflammatory processes to tissue lesioning. Epidemiological and experimental data suggest the potential involvement of specific agents as neurotoxicants (e.g. pesticides) or neuroprotective compounds (e.g. tobacco products) in the pathogenesis of nigrostriatal degeneration, further supporting a relationship between the environment and Parkinson's disease. A likely scenario that emerges from our current knowledge is that neurodegeneration results from multiple events and interactive mechanisms. These may include (i) the synergistic action of endogenous and exogenous toxins (e.g. the ability of the pesticide diethyldithiocarbamate to promote the toxicity of other compounds); (ii) the interactions of toxic agents with endogenous elements (e.g. the protein alpha-synuclein); (iii) the tissue response to an initial toxic insult; and, last but not least, (iv) the effects of environmental factors on the background of genetic predisposition and aging. (C) 2002 Elsevier Science Inc. All rights reserved.