Martins-Ferreira Ricardo, Leal Bárbara Guerra, Costa Paulo Pinho
Epigenetics and Immune Disease Group, Josep Carreras Research Institute (IJC), Barcelona, Spain.
Immunogenetics Lab, Molecular Pathology and Immunology, Instituto de Ciências Biomédicas Abel Salazar-Universidade do Porto (ICBAS-UPorto), Porto, Portugal.
Front Cell Neurosci. 2022 Mar 24;16:852151. doi: 10.3389/fncel.2022.852151. eCollection 2022.
Circulating cell-free DNA (cfDNA) are highly degraded DNA fragments shed into the bloodstream. Apoptosis is likely to be the main source of cfDNA due to the matching sizes of cfDNA and apoptotic DNA cleavage fragments. The study of cfDNA in liquid biopsies has served clinical research greatly. Genetic analysis of these circulating fragments has been used in non-invasive prenatal testing, detection of graft rejection in organ transplants, and cancer detection and monitoring. cfDNA sequencing is, however, of limited value in settings in which genetic association is not well-established, such as most neurodegenerative diseases.Recent studies have taken advantage of the cell-type specificity of DNA methylation to determine the tissue of origin, thus detecting ongoing cell death taking place in specific body compartments. Such an approach is yet to be developed in the context of epilepsy research. In this article, we review the different approaches that have been used to monitor cell-type specific death through DNA methylation analysis, and recent data detecting neuronal death in neuropathological settings. We focus on the potential relevance of these tools in focal epilepsies, like Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis (MTLE-HS), characterized by severe neuronal loss. We speculate on the potential relevance of cfDNA methylation screening for the detection of neuronal cell death in individuals with high risk of epileptogenesis that would benefit from early diagnosis and consequent early treatment.
循环游离DNA（cfDNA）是释放入血液中的高度降解的DNA片段。由于cfDNA与凋亡DNA裂解片段大小匹配，凋亡很可能是cfDNA的主要来源。液体活检中cfDNA的研究对临床研究有很大帮助。这些循环片段的基因分析已用于无创产前检测、器官移植中移植排斥反应的检测以及癌症检测和监测。然而，在遗传关联尚未明确的情况下，如大多数神经退行性疾病，cfDNA测序的价值有限。最近的研究利用DNA甲基化的细胞类型特异性来确定起源组织，从而检测特定身体部位正在发生的细胞死亡。在癫痫研究中尚未开发出这样的方法。在本文中，我们回顾了通过DNA甲基化分析监测细胞类型特异性死亡所使用的不同方法，以及在神经病理学背景下检测神经元死亡的最新数据。我们重点关注这些工具在局灶性癫痫中的潜在相关性，如伴有海马硬化的内侧颞叶癫痫（MTLE-HS），其特征是严重的神经元丢失。我们推测cfDNA甲基化筛查对于检测有癫痫发生高风险且将受益于早期诊断和后续早期治疗的个体中神经元细胞死亡的潜在相关性。
