| First Author | Kishi N | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 10520 | PubMed ID | 26821816 |
| Mgi Jnum | J:236294 | Mgi Id | MGI:5805632 |
| Doi | 10.1038/ncomms10520 | Citation | Kishi N, et al. (2016) Reduction of aberrant NF-kappaB signalling ameliorates Rett syndrome phenotypes in Mecp2-null mice. Nat Commun 7:10520 |
| abstractText | Mutations in the transcriptional regulator Mecp2 cause the severe X-linked neurodevelopmental disorder Rett syndrome (RTT). In this study, we investigate genes that function downstream of MeCP2 in cerebral cortex circuitry, and identify upregulation of Irak1, a central component of the NF-kappaB pathway. We show that overexpression of Irak1 mimics the reduced dendritic complexity of Mecp2-null cortical callosal projection neurons (CPN), and that NF-kappaB signalling is upregulated in the cortex with Mecp2 loss-of-function. Strikingly, we find that genetically reducing NF-kappaB signalling in Mecp2-null mice not only ameliorates CPN dendritic complexity but also substantially extends their normally shortened lifespan, indicating broader roles for NF-kappaB signalling in RTT pathogenesis. These results provide new insight into both the fundamental neurobiology of RTT, and potential therapeutic strategies via NF-kappaB pathway modulation. |
