Tongji School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China.
Arch Biochem Biophys. 2021 Mar 30;700:108768. doi: 10.1016/j.abb.2021.108768. Epub 2021 Jan 21.
Numerous neurological and non-neurological disorders are associated with dysfunction of epigenetic modulators, and methyl CpG binding protein 2 (MeCP2) is one of such proteins. Initially identified as a transcriptional repressor, MeCP2 specifically binds to methylated DNA, and mutations of MeCP2 have been shown to cause Rett syndrome (RTT), a severe neurological disorder. Recently, accumulating evidence suggests that ubiquitously expressed MeCP2 also plays a central role in non-neurological disorders including cardiac dysfunction, liver injury, respiratory disorders, urological dysfunction, adipose tissue metabolism disorders, movement abnormality and inflammatory responses in a DNA methylation dependent or independent manner. Despite significant progresses in our understanding of MeCP2 over the last few decades, there is still a considerable knowledge gap to translate the in vitro and in vivo experimental findings into therapeutic interventions. In this review, we provide a synopsis of the role of MeCP2 in the pathophysiology of non-neurological disorders, MeCP2-based research directions and therapeutic strategies for non-neurological disorders are also discussed.
许多神经和非神经疾病都与表观遗传调节剂的功能障碍有关，甲基 CpG 结合蛋白 2（MeCP2）就是这样的一种蛋白。MeCP2 最初被鉴定为一种转录抑制剂，它特异性地与甲基化 DNA 结合，并且已经证明 MeCP2 的突变会导致雷特综合征（RTT），这是一种严重的神经疾病。最近，越来越多的证据表明，广泛表达的 MeCP2 也在包括心脏功能障碍、肝损伤、呼吸障碍、尿功能障碍、脂肪组织代谢障碍、运动异常和炎症反应在内的非神经疾病中发挥核心作用，这种作用是通过 DNA 甲基化依赖或非依赖的方式发挥的。尽管在过去几十年中我们对 MeCP2 的理解取得了重大进展，但仍有相当大的知识空白需要将体外和体内实验结果转化为治疗干预措施。在这篇综述中，我们概述了 MeCP2 在非神经疾病的病理生理学中的作用，还讨论了基于 MeCP2 的非神经疾病的研究方向和治疗策略。
