Dept Pathology, Germans Trias i Pujol Research Institute, 08916 Badalona, Spain.
Int J Mol Sci. 2020 Jul 2;21(13):4718. doi: 10.3390/ijms21134718.
Lewy body disorders (LBD) include Parkinson's disease (PD) and dementia with Lewy bodies (DLB). They are synucleinopathies with a heterogeneous clinical manifestation. As a cause of neuropathological overlap with other neurodegenerative diseases, the establishment of a correct clinical diagnosis is still challenging, and clinical management may be difficult. The combination of genetic variation and epigenetic changes comprising gene expression-modulating DNA methylation and histone alterations modifies the phenotype, disease course, and susceptibility to disease. In this review, we summarize the results achieved in the deciphering of the LBD epigenome. To provide an appropriate context, first LBD genetics is briefly outlined. Afterwards, a detailed review of epigenetic modifications identified for LBD in human cells, postmortem, and peripheral tissues is provided. We also focus on the difficulty of identifying epigenome-related biomarker candidates and discuss the results obtained so far. Additionally, epigenetic changes as therapeutic targets, as well as different epigenome-based treatments, are revised. The number of studies focusing on PD is relatively limited and practically inexistent for DLB. There is a lack of replication studies, and some results are even contradictory, probably due to differences in sample collection and analytical techniques. In summary, we show the current achievements and directions for future research.
路易体障碍（LBD）包括帕金森病（PD）和路易体痴呆（DLB）。它们是具有异质性临床表现的突触核蛋白病。由于与其他神经退行性疾病存在病理重叠的原因，正确的临床诊断仍然具有挑战性，临床管理可能也较为困难。遗传变异和表观遗传变化的组合，包括基因表达调节的 DNA 甲基化和组蛋白改变，改变了表型、疾病过程和易感性。在这篇综述中，我们总结了破译 LBD 表观基因组所取得的成果。为了提供适当的背景，首先简要概述了 LBD 遗传学。随后，详细回顾了在人类细胞、死后和外周组织中确定的与 LBD 相关的表观遗传修饰。我们还重点关注了识别与表观基因组相关的生物标志物候选物的困难，并讨论了迄今为止获得的结果。此外，还回顾了作为治疗靶点的表观遗传变化以及不同的基于表观基因组的治疗方法。关注 PD 的研究数量相对较少，而关注 DLB 的则几乎没有。缺乏复制研究，有些结果甚至相互矛盾，这可能是由于样本收集和分析技术的差异所致。总之，我们展示了当前的成就和未来研究的方向。
