Miranda-Morales Ernesto, Meier Karin, Sandoval-Carrillo Ada, Salas-Pacheco José, Vázquez-Cárdenas Paola, Arias-Carrión Oscar
Unidad de Trastornos del Movimiento y Sueño, Hospital General Dr. Manuel Gea GonzálezMexico City, Mexico.
Instituto de Investigación Científica, Universidad Juárez del Estado de DurangoDurango, Mexico.
Front Mol Neurosci. 2017 Jul 18;10:225. doi: 10.3389/fnmol.2017.00225. eCollection 2017.
It has been 200 years since Parkinson's disease (PD) was first described, yet many aspects of its etiopathogenesis remain unclear. PD is a progressive and complex neurodegenerative disorder caused by genetic and environmental factors including aging, nutrition, pesticides and exposure to heavy metals. DNA methylation may be altered in response to some of these factors; therefore, it is proposed that epigenetic mechanisms, particularly DNA methylation, can have a fundamental role in gene-environment interactions that are related with PD. Epigenetic changes in PD-associated genes are now widely studied in different populations, to discover the mechanisms that contribute to disease development and identify novel biomarkers for early diagnosis and future pharmacological treatment. While initial studies sought to find associations between promoter DNA methylation and the regulation of associated genes in PD brain tissue, more recent studies have described concordant DNA methylation patterns between blood and brain tissue DNA. These data justify the use of peripheral blood samples instead of brain tissue for epigenetic studies. Here, we summarize the current data about DNA methylation changes in PD and discuss the potential of DNA methylation as a potential biomarker for PD. Additionally, we discuss environmental and nutritional factors that have been implicated in DNA methylation. Although the search for significant DNA methylation changes and gene expression analyses of PD-associated genes have yielded inconsistent and contradictory results, epigenetic modifications remain under investigation for their potential to reveal the link between environmental risk factors and the development of PD.
帕金森病(PD)首次被描述至今已有200年,但该病的病因发病机制仍有许多方面尚不清楚。PD是一种由遗传和环境因素引起的进行性复杂神经退行性疾病,这些因素包括衰老、营养、农药和重金属暴露。DNA甲基化可能会因其中一些因素而发生改变;因此,有人提出表观遗传机制,特别是DNA甲基化,在与PD相关的基因-环境相互作用中可能起重要作用。目前,不同人群广泛研究了PD相关基因的表观遗传变化,以发现导致疾病发展的机制,并确定用于早期诊断和未来药物治疗的新型生物标志物。虽然最初的研究试图寻找启动子DNA甲基化与PD脑组织中相关基因调控之间的关联,但最近的研究描述了血液和脑组织DNA之间一致的DNA甲基化模式。这些数据证明了在外周血样本而非脑组织中进行表观遗传学研究的合理性。在此,我们总结了目前关于PD中DNA甲基化变化的数据,并讨论了DNA甲基化作为PD潜在生物标志物的潜力。此外,我们还讨论了与DNA甲基化有关的环境和营养因素。尽管对PD相关基因显著DNA甲基化变化的研究和基因表达分析产生了不一致和矛盾的结果,但表观遗传修饰因其揭示环境危险因素与PD发展之间联系的潜力仍在研究中。