Department of Pharmacology and Toxicology, Medical College of Georgia, Georgia Regents University, 1459 Laney Walker Blvd, CB-3618, 30912, Augusta, Georgia.
Neurotherapeutics. 2013 Oct;10(4):698-708. doi: 10.1007/s13311-013-0211-8.
Parkinson's disease (PD) is a complex multifactorial disorder marked by extensive system-wide pathology, including a substantial loss of nigrostriatal dopaminergic neurons. The etiology of PD remains elusive, but there is considerable evidence that, in addition to well-defined genetic mechanisms environmental factors play a crucial role in disease pathogenesis. How the environment might influence the genetic factors and contribute to disease development and progression remains unclear. In recent years, epigenetic mechanisms such as DNA methylation, chromatin remodeling and alterations in gene expression via non-coding RNAs have begun to be revealed as potential factors in PD pathogenesis. Epigenetic modulation exists throughout life, beginning in prenatal stages, is dependent on the lifestyle, environmental exposure and genetic makeup of an individual and may serve as a missing link between PD risk factors and development of the disease. This chapter sheds light on the emerging role of epigenetics in disease pathogenesis and on prospective interventional strategies for the therapeutic modulation of PD.
帕金森病（PD）是一种复杂的多因素疾病，其特征是广泛的全身性病理学，包括黑质纹状体多巴胺能神经元的大量丧失。PD 的病因仍然难以捉摸，但有相当多的证据表明，除了明确的遗传机制外，环境因素在疾病发病机制中起着至关重要的作用。环境如何影响遗传因素以及如何促进疾病的发展和进展尚不清楚。近年来，DNA 甲基化、染色质重塑以及非编码 RNA 介导的基因表达改变等表观遗传机制已开始被揭示为 PD 发病机制中的潜在因素。表观遗传调控贯穿人的一生，从产前阶段开始，取决于个体的生活方式、环境暴露和遗传构成，并可能成为 PD 风险因素与疾病发展之间缺失的环节。本章探讨了表观遗传学在疾病发病机制中的新作用，以及针对 PD 的治疗性调节的潜在干预策略。
