Rett syndrome: insights into genetic, molecular and circuit mechanisms
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 re...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Springer Science and Business Media LLC
2020
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| Online Access: | https://hdl.handle.net/1721.1/127274 |
| _version_ | 1826205539524149248 |
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| author | Ip, Pak Kan Mellios, Nikolaos Sur, Mriganka |
| author2 | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences |
| author_facet | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Ip, Pak Kan Mellios, Nikolaos Sur, Mriganka |
| author_sort | Ip, Pak Kan |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T13:15:03Z |
| format | Article |
| id | mit-1721.1/127274 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T13:15:03Z |
| publishDate | 2020 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1272742022-10-01T14:00:12Z Rett syndrome: insights into genetic, molecular and circuit mechanisms Ip, Pak Kan Mellios, Nikolaos Sur, Mriganka Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Picower Institute for Learning and Memory 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. National Institutes of Health (Grants MH085802 and EY007023) 2020-09-15T19:38:09Z 2020-09-15T19:38:09Z 2018-05 2019-10-04T13:15:32Z Article http://purl.org/eprint/type/JournalArticle 1471-003X 1471-0048 https://hdl.handle.net/1721.1/127274 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. en http://dx.doi.org/10.1038/s41583-018-0006-3 Nature Reviews Neuroscience Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Springer Science and Business Media LLC PMC |
| spellingShingle | Ip, Pak Kan Mellios, Nikolaos Sur, Mriganka Rett syndrome: insights into genetic, molecular and circuit mechanisms |
| title | Rett syndrome: insights into genetic, molecular and circuit mechanisms |
| title_full | Rett syndrome: insights into genetic, molecular and circuit mechanisms |
| title_fullStr | Rett syndrome: insights into genetic, molecular and circuit mechanisms |
| title_full_unstemmed | Rett syndrome: insights into genetic, molecular and circuit mechanisms |
| title_short | Rett syndrome: insights into genetic, molecular and circuit mechanisms |
| title_sort | rett syndrome insights into genetic molecular and circuit mechanisms |
| url | https://hdl.handle.net/1721.1/127274 |
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