Rett syndrome: insights into genetic, molecular and circuit mechanisms
Name
nihms-1008070.pdf
Description
Accepted version
Size
1.13 MB
Format
Adobe PDF
Checksum (MD5)
31d9421fbc054a69f5510e78cafc01dd
Author(s)
Ip, Pak Kan
Mellios, Nikolaos
Sur, Mriganka
Date Issued
May 2018
Journal
Nature Reviews Neuroscience
Publisher
Springer Science and Business Media LLC
Citation
Ip, Jacque P. K. et al. "Rett syndrome: insights into genetic, molecular and circuit mechanisms." Nature Reviews Neuroscience 19, 6 (May 2018): 368–382 © 2018 Macmillan Publishers Ltd., part of Springer Nature.
Version
Author's final manuscript
Abstract
Rett syndrome (RTT) is a severe neurological disorder caused by mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2). Almost two decades of research into RTT have greatly advanced our understanding of the function and regulation of the multifunctional protein MeCP2. Here, we review recent advances in understanding how loss of MeCP2 impacts different stages of brain development, discuss recent findings demonstrating the molecular role of MeCP2 as a transcriptional repressor, assess primary and secondary effects of MeCP2 loss and examine how loss of MeCP2 can result in an imbalance of neuronal excitation and inhibition at the circuit level along with dysregulation of activity-dependent mechanisms. These factors present challenges to the search for mechanism-based therapeutics for RTT and suggest specific approaches that may be more effective than others.
MIT Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Picower Institute for Learning and Memory
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1038/s41583-018-0006-3
