Mechanisms of Gene-Environment Interactions in Parkinson's Disease.
Mechanisms of Gene-Environment Interactions in Parkinson's Disease.
复制标题
帕金森病的基因-环境相互作用机制
DOI：
10.1007/s40572-017-0143-2
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发表时间：
2017-06-01
影响因子：
7.9
通讯作者：
Fleming, Sheila M
中科院分区：
文献类型：
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作者：
Fleming, Sheila M
综述目的：本研究的目的是讨论与导致帕金森病 (PD) 发展的环境和遗传因素相关的主要机制。最新发现：除了新的环境因素外，正在快速确定导致帕金森病的新的遗传因素。 α-突触核蛋白和富含亮氨酸重复激酶 2 的突变导致遗传性帕金森病的发现，以及将除草剂、杀虫剂和金属确定为危险因素的流行病学、体外和体内研究，极大地提高了我们对帕金森病发生机制的理解。然而，与此同时，这些发现也增加了这种疾病的复杂性。在过去的几年里，与帕金森病相关的遗传学在许多方面主导了该领域。然而，大多数帕金森病病例可能是由于环境暴露和遗传易感性的不同组合造成的。用于模拟 PD 的最常见毒物包括鱼藤酮、百草枯和 1-甲基-4-苯基-1,2,3,6-四氢吡啶，已被证明与许多与 PD 相关的基因（例如 α-突触核蛋白）相互作用。因此，了解遗传和环境因素之间的共同机制对于早期发现和成功转化潜在疗法至关重要，这是最终目标。
PURPOSE OF REVIEW: The purpose of the study was to discuss the main mechanisms associated with environmental and genetic factors that contribute to the development of Parkinson's disease (PD).RECENT FINDINGS: Novel genetic contributors to PD are being identified at a rapid pace in addition to novel environmental factors. The discovery of mutations in alpha-synuclein and leucine-rich repeat kinase 2 causing inherited forms of PD along with epidemiological, in vitro, and in vivo studies identifying herbicides, pesticides, and metals as risk factors have dramatically improved our understanding of mechanisms involved in the development of PD. However, at the same time, these discoveries have also added layers of complexity to the disease. Within the last several years, the genetics associated with PD has dominated the field in many ways; however, the majority of PD cases are likely due to different combinations of environmental exposures and genetic susceptibility. The most common toxicants used to model PD including rotenone, paraquat, and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine have been shown to interact with many of the genes linked with PD such as alpha-synuclein. Therefore, an understanding of mechanisms common between genetic and environmental factors is essential for early detection and successful translation of potential therapies, which is the ultimate goal.