Insights into neurons that cause symptoms of Rett syndrome could guide new therapy search
(eLife ) Two studies in mice from Baylor College of Medicine, Texas, reveal new insights into neurons that mediate symptoms typical of the postnatal neurological disorder Rett syndrome.
Publication date: 24 March 2020Source: Cell Reports, Volume 30, Issue 12Author(s): Deivid C. Rodrigues, Marat Mufteev, Robert J. Weatheritt, Ugljesa Djuric, Kevin C.H. Ha, P. Joel Ross, Wei Wei, Alina Piekna, Maria A. Sartori, Loryn Byres, Rebecca S.F. Mok, Kirill Zaslavsky, Peter Pasceri, Phedias Diamandis, Quaid Morris, Benjamin J. Blencowe, James Ellis
Abstract Structural Maintenance of Chromosomes (SMCs) are part of a large family of ring complexes that participates in a number of DNA transactions. Among SMCs, SMC1A gene is unique. It encodes a subunit of the cohesin-core complex that tethers sister chromatids together to ensure correct chromosome segregation in both mitosis and meiosis. As a member of the cohesin ring, SMC1A takes part in gene transcription regulation and genome organization; and it participates in the DNA Damage Repair (DDR) pathway, being phosphorylated by Ataxia Telangiectasia Mutated (ATM) and Ataxia Telangiectasia and Rad3 Related (ATR) t...
Rett syndrome is an incurable neurodevelopmental disorder caused by mutations in the gene encoding for methyl-CpG binding-protein 2 (MeCP2). Gene therapy for this disease presents inherent hurdles sinceMECP2 is expressed throughout the brain and its duplication leads to severe neurological conditions as well. Herein, we use the AAV-PHP.eB to deliver an instability-proneMecp2 (iMecp2) transgene cassette which, increasing RNA destabilization and inefficient protein translation of the viralMecp2transgene, limits supraphysiological Mecp2 protein levels. Intravenous injections of the PHP.eB-iMecp2 virus in symptomaticMecp2 muta...
Authors: Provvidenziale L, Cinotti E, Campoli M, Russo F, Rubegni P PMID: 32163043 [PubMed - as supplied by publisher]
Condition: Rett Syndrome Interventions: Drug: ANAVEX2-73 oral liquid; Drug: Placebo oral liquid Sponsors: Anavex Life Sciences Corp.; Anavex Australia Pty Ltd.; Anavex Germany GmbH Recruiting
Methylated cytosine is an effector of epigenetic gene regulation. In the brain, Dnmt3a is the sole ‘writer’ of atypical non-CpG methylation (mCH), and MeCP2 is the only known ‘reader’ for mCH. We asked if MeCP2 is the sole reader for Dnmt3a dependent methylation by comparing mice lacking either protein in GABAergic inhibitory neurons. Loss of either protein causes overlapping and distinct features from the behavioral to molecular level. Loss of Dnmt3a causes global loss of mCH and a subset of mCG sites resulting in more widespread transcriptional alterations and severe neurological dysfunction than ...
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Conclusion Our study showed sleep dysfunction to be less prevalent in RTT-affected individuals than evidence from past studies has suggested. Nevertheless, this remains a subjective assessment of sleep quality and therefore the need to find objective, disorder-specific parameters that measure sleep quality in RTT patients persists. [...] Georg Thieme Verlag KG Stuttgart · New YorkArticle in Thieme eJournals: Table of contents | Abstract | Full text