Division of Medical Sciences, University of Victoria, Victoria, BC V8W 2Y2, Canada.
Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC V8W 3P6, Canada.
Cells. 2022 Feb 21;11(4):748. doi: 10.3390/cells11040748.
Methyl-CpG-binding protein 2 (MeCP2) is a transcriptional regulator that is highly abundant in the brain. It binds to methylated genomic DNA to regulate a range of physiological functions implicated in neuronal development and adult synaptic plasticity. MeCP2 has mainly been studied for its role in neurodevelopmental disorders, but alterations in MeCP2 are also present in stress-related disorders such as major depression. Impairments in both stress regulation and synaptic plasticity are associated with depression, but the specific mechanisms underlying these changes have not been identified. Here, we review the interplay between stress, synaptic plasticity, and MeCP2. We focus our attention on the transcriptional regulation of important neuronal plasticity genes such as BDNF and reelin (RELN). Moreover, we provide evidence from recent studies showing a link between chronic stress-induced depressive symptoms and dysregulation of MeCP2 expression, underscoring the role of this protein in stress-related pathology. We conclude that MeCP2 is a promising target for the development of novel, more efficacious therapeutics for the treatment of stress-related disorders such as depression.
甲基化 CpG 结合蛋白 2（MeCP2）是一种在大脑中高度丰富的转录调节剂。它与甲基化的基因组 DNA 结合，调节涉及神经元发育和成年突触可塑性的一系列生理功能。MeCP2 主要因其在神经发育障碍中的作用而被研究，但应激相关障碍（如重度抑郁症）中也存在 MeCP2 的改变。应激调节和突触可塑性的损伤都与抑郁症有关，但这些变化的具体机制尚未确定。在这里，我们回顾了应激、突触可塑性和 MeCP2 之间的相互作用。我们将注意力集中在 BDNF 和 reelin（RELN）等重要神经元可塑性基因的转录调控上。此外，我们提供了最近的研究证据，表明慢性应激引起的抑郁症状与 MeCP2 表达失调之间存在联系，突出了这种蛋白质在应激相关病理中的作用。我们得出结论，MeCP2 是开发新型、更有效的应激相关障碍（如抑郁症）治疗方法的有前途的靶点。
