González Molina Luis A, Dolga Amalia M, Rots Marianne G, Sarno Federica
Epigenetic Editing, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Molecular Pharmacology, Faculty of Science and Engineering, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, The Netherlands.
Subcell Biochem. 2025;108:111-190. doi: 10.1007/978-3-031-75980-2_4.
Brain disorders, especially neurodegenerative diseases, affect millions of people worldwide. There is no causal treatment available; therefore, there is an unmet clinical need for finding therapeutic options for these diseases. Epigenetic research has resulted in identification of various genomic loci with differential disease-specific epigenetic modifications, mainly DNA methylation. These biomarkers, although not yet translated into clinically approved options, offer therapeutic targets as epigenetic modifications are reversible. Indeed, clinical trials are designed to inhibit epigenetic writers, erasers, or readers using epigenetic drugs to interfere with epigenetic dysregulation in brain disorders. However, since such drugs elicit genome-wide effects and potentially cause toxicity, the recent developments in the field of epigenetic editing are gaining widespread attention. In this review, we provide examples of epigenetic biomarkers and epi-drugs, while describing efforts in the field of epigenetic editing, to eventually make a difference for the currently incurable brain disorders.
脑部疾病，尤其是神经退行性疾病，影响着全球数百万人。目前尚无因果性治疗方法；因此，临床上迫切需要为这些疾病找到治疗方案。表观遗传学研究已鉴定出各种具有不同疾病特异性表观遗传修饰的基因组位点，主要是DNA甲基化。这些生物标志物虽然尚未转化为临床认可的方案，但由于表观遗传修饰是可逆的，因此提供了治疗靶点。事实上，临床试验旨在使用表观遗传药物抑制表观遗传书写蛋白、擦除蛋白或读取蛋白，以干扰脑部疾病中的表观遗传失调。然而，由于这类药物会引发全基因组效应并可能导致毒性，表观遗传编辑领域的最新进展正受到广泛关注。在这篇综述中，我们列举了表观遗传生物标志物和表观遗传药物的实例，同时描述了表观遗传编辑领域的研究工作，以期最终为目前无法治愈的脑部疾病带来改变。
