MeCP2 Deficiency in Neuroglia: New Progress in the Pathogenesis of Rett Syndrome.
MeCP2 Deficiency in Neuroglia: New Progress in the Pathogenesis of Rett Syndrome.
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DOI：
10.3389/fnmol.2017.00316
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发表时间：
2017
影响因子：
4.8
通讯作者：
Xiao L
中科院分区：
文献类型：
--
作者：
Jin XR;Chen XS;Xiao L
Rett综合征（RTT）是一种X连锁神经发育疾病，主要由甲基CpG结合蛋白2（MeCP 2）基因突变引起。通常，RTT被归因于以神经元为中心的功能障碍。然而，越来越多的证据表明，胶质细胞异常也参与RTT的发病机制。在神经胶质细胞中特别是MeCP 2-null的小鼠显示出与在MeCP 2-null小鼠（RTT的小鼠模型）中发现的那些相似的行为和/或神经元异常。星形胶质细胞中的MeCP 2缺乏影响胶质细胞中间丝蛋白如胶质酸性蛋白（GFAP）和S100的表达，并通过干扰谷氨酸代谢或增强微管不稳定性诱导神经元毒性。少突胶质细胞（OLs）中MeCP 2缺乏导致髓鞘基因表达下调并影响髓鞘形成。而MeCP 2缺陷的小胶质细胞不能响应环境刺激，释放过量的谷氨酸，并加重神经元回路的损伤。本文就MeCP 2在RTT相关胶质细胞中的作用进行综述，以期为RTT的治疗提供新的思路。
Rett syndrome (RTT) is an X-linked neurodevelopmental disease predominantly caused by mutations of the methyl-CpG-binding protein 2 (MeCP2) gene. Generally, RTT has been attributed to neuron-centric dysfunction. However, increasing evidence has shown that glial abnormalities are also involved in the pathogenesis of RTT. Mice that are MeCP2-null specifically in glial cells showed similar behavioral and/or neuronal abnormalities as those found in MeCP2-null mice, a mouse model of RTT. MeCP2 deficiency in astrocytes impacts the expression of glial intermediate filament proteins such as fibrillary acidic protein (GFAP) and S100 and induces neuron toxicity by disturbing glutamate metabolism or enhancing microtubule instability. MeCP2 deficiency in oligodendrocytes (OLs) results in down-regulation of myelin gene expression and impacts myelination. While MeCP2-deficient microglia cells fail in response to environmental stimuli, release excessive glutamate, and aggravate impairment of the neuronal circuit. In this review, we mainly focus on the progress in determining the role of MeCP2 in glial cells involved in RTT, which may provide further insight into a therapeutic intervention for RTT.
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