Inhibition of Gsk3b Reduces Nfkb1 Signaling and Rescues Synaptic Activity to Improve the Rett Syndrome Phenotype in Mecp2-Knockout Mice
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چکیده
منابع مشابه
Expression of MeCP2 in postmitotic neurons rescues Rett syndrome in mice.
Mutations in MECP2 are the cause of Rett syndrome (RTT) in humans, a neurodevelopmental disorder that affects mainly girls. MeCP2 is a protein that binds CpG dinucleotides and is thought to act as a global transcriptional repressor. It is highly expressed in neurons, but not in glia, of the postnatal brain. The timing of MeCP2 activation correlates with the maturation of the central nervous sys...
متن کاملMECP2 deletions and genotype-phenotype correlation in Rett syndrome.
Rett syndrome is a neurodevelopmental disorder that represents one of the most common genetic causes of mental retardation in girls. MECP2 point mutations in exons 2-4 account for about 80% of classic Rett cases and for a lower percentage of variant patients. We investigated the genetic cause in 77 mutation-negative Rett patients (33 classic, 31 variant, and 13 Rett-like cases) by searching mis...
متن کاملMeCP2 SUMOylation rescues Mecp2-mutant-induced behavioural deficits in a mouse model of Rett syndrome
The methyl-CpG-binding protein 2 (MeCP2) gene, MECP2, is an X-linked gene encoding the MeCP2 protein, and mutations of MECP2 cause Rett syndrome (RTT). However, the molecular mechanism of MECP2-mutation-caused RTT is less known. Here we find that MeCP2 could be SUMO-modified by the E3 ligase PIAS1 at Lys-412. MeCP2 phosphorylation (at Ser-421 and Thr-308) facilitates MeCP2 SUMOylation, and MeCP...
متن کاملThe Rett syndrome protein MeCP2 regulates synaptic scaling.
Synaptic scaling is a form of homeostatic synaptic plasticity characterized by cell-wide changes in synaptic strength in response to changes in overall levels of neuronal activity. Here we report that bicuculline-induced increase in neuronal activity leads to a decrease in mEPSC amplitude and a decrease in expression of the AMPA receptor subunit GluR2 in rat hippocampal cultures. Bicuculline tr...
متن کاملRett syndrome and the MECP2 gene.
First described by Andreas Rett in 1966, Rett syndrome is a severe neurodevelopmental disorder which almost exclusively aVects females. A genetic aetiology was suggested by MZ twin concordance and a case of vertical transmission of the disorder. Although the prevalence is between 1 in 10 000 and 1 in 15 000 female births, >95% of cases arise de novo so the disorder has been considered to be an ...
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ژورنال
عنوان ژورنال: Cell Reports
سال: 2018
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2018.04.010