Cargando…
MeCP2 Deficiency in Neuroglia: New Progress in the Pathogenesis of Rett Syndrome
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...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5632713/ https://www.ncbi.nlm.nih.gov/pubmed/29046627 http://dx.doi.org/10.3389/fnmol.2017.00316 |
_version_ | 1783269750416080896 |
---|---|
author | Jin, Xu-Rui Chen, Xing-Shu Xiao, Lan |
author_facet | Jin, Xu-Rui Chen, Xing-Shu Xiao, Lan |
author_sort | Jin, Xu-Rui |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5632713 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-56327132017-10-18 MeCP2 Deficiency in Neuroglia: New Progress in the Pathogenesis of Rett Syndrome Jin, Xu-Rui Chen, Xing-Shu Xiao, Lan Front Mol Neurosci Neuroscience 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. Frontiers Media S.A. 2017-10-04 /pmc/articles/PMC5632713/ /pubmed/29046627 http://dx.doi.org/10.3389/fnmol.2017.00316 Text en Copyright © 2017 Jin, Chen and Xiao. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Jin, Xu-Rui Chen, Xing-Shu Xiao, Lan MeCP2 Deficiency in Neuroglia: New Progress in the Pathogenesis of Rett Syndrome |
title | MeCP2 Deficiency in Neuroglia: New Progress in the Pathogenesis of Rett Syndrome |
title_full | MeCP2 Deficiency in Neuroglia: New Progress in the Pathogenesis of Rett Syndrome |
title_fullStr | MeCP2 Deficiency in Neuroglia: New Progress in the Pathogenesis of Rett Syndrome |
title_full_unstemmed | MeCP2 Deficiency in Neuroglia: New Progress in the Pathogenesis of Rett Syndrome |
title_short | MeCP2 Deficiency in Neuroglia: New Progress in the Pathogenesis of Rett Syndrome |
title_sort | mecp2 deficiency in neuroglia: new progress in the pathogenesis of rett syndrome |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5632713/ https://www.ncbi.nlm.nih.gov/pubmed/29046627 http://dx.doi.org/10.3389/fnmol.2017.00316 |
work_keys_str_mv | AT jinxurui mecp2deficiencyinneuroglianewprogressinthepathogenesisofrettsyndrome AT chenxingshu mecp2deficiencyinneuroglianewprogressinthepathogenesisofrettsyndrome AT xiaolan mecp2deficiencyinneuroglianewprogressinthepathogenesisofrettsyndrome |