Dieldrin-induced neurotoxicity: Relevance to Parkinson's disease pathogenesis
Dieldrin-induced neurotoxicity: Relevance to Parkinson's disease pathogenesis
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DOI：
10.1016/j.neuro.2004.07.010
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发表时间：
2005-08-01
期刊：
影响因子：
3.4
通讯作者：
Anantharam, V
中科院分区：
文献类型：
--
作者：
Kanthasamy, AG;Kitazawa, M;Anantharam, V
帕金森病（PD）是一种与环境化学物质暴露密切相关的神经退行性疾病。最近的流行病学数据表明，环境危险因素可能发挥主导作用，相比遗传因素在特发性帕金森病的发病机制。关键遗传缺陷的鉴定，如α-突触核蛋白和帕金森突变，也强调了遗传因素在疾病中的重要作用。因此，了解PD中基因和环境之间的相互作用对于解开这种具有200年历史的神经退行性疾病的奥秘至关重要。农药和金属是最常见的一类环境化学品，促进多巴胺能变性。在人PD死后脑组织中发现了有机氯农药狄氏剂，这表明这种农药有可能促进黑质细胞死亡。尽管狄氏剂已被禁用，但由于农药在环境中的持续积累，人类继续通过受污染的乳制品和肉类接触农药。这篇综述总结了各种神经毒性的研究进行细胞培养和动物模型后狄氏剂暴露，并讨论了其相关性的关键病理机制与黑质多巴胺能变性，包括氧化应激，线粒体功能障碍，蛋白质聚集和细胞凋亡。(c)2004年爱思唯尔公司All rights reserved.
Parkinson's disease (PD) is increasingly recognized as a neurodegenerative disorder strongly associated with environmental chemical exposures. Recent epidemiological data demonstrate that environmental risk factors may play a dominant role as compared to genetic factors in the etiopathogenesis of idiopathic Parkinson's disease. Identification of key genetic defects such as alpha-synuclein and parkin mutations in PD also underscores the important role of genetic factors in the disease. Thus, understanding the interplay between genes and environment in PD may be critical to unlocking the mysteries of this 200-year-old neurodegenerative disease. Pesticides and metals are the most common classes of environmental chemicals that promote dopaminergic degeneration. The organochlorine pesticide dieldrin has been found in human PD postmortem brain tissues, suggesting that this pesticide has potential to promote nigral cell death. Though dieldrin has been banned, humans continue to be exposed to the pesticide through contaminated dairy products and meats due to the persistent accumulation of the pesticide in the environment. This review summarizes various neurotoxic studies conducted in both cell culture and animals models following dieldrin exposure and discusses their relevance to key pathological mechanisms associated with nigral dopaminergic degeneration including oxidative stress, mitochondrial dysfunction, protein aggregation, and apoptosis. (c) 2004 Elsevier Inc. All rights reserved.