Rett syndrome and the urge of novel approaches to study MeCP2 functions and mechanisms of action

Francesco Bedogni, Riccardo L. Rossi, Francesco Galli, Clementina Cobolli Gigli, Anna Gandaglia, Charlotte Kilstrup-Nielsen, Nicoletta Landsberger

Research output: Contribution to journalArticle

Abstract

Rett syndrome (RTT) is a devastating genetic disorder that worldwide represents the most common genetic cause of severe intellectual disability in females. Most cases are caused by mutations in the X-linked MECP2 gene. Several recent studies have demonstrated that RTT mimicking animal models do not develop an irreversible condition and phenotypic rescue is possible. However, no cure for RTT has been identified so far, and patients are only given symptomatic and supportive treatments. The development of clinical applications imposes a more comprehensive knowledge of MeCP2 functional role(s) and their relevance for RTT pathobiology. Herein, we thoroughly survey the knowledge about MeCP2 structure and functions, highlighting the necessity of identifying more functional domains and the value of molecular genetics. Given that, in our opinion, RTT ultimately is generated by perturbations in gene transcription and so far no genes/pathways have been consistently linked to a dysfunctional MeCP2, we have used higher-level bioinformatic analyses to identify commonly deregulated mechanisms in MeCP2-defective samples. In this review we present our results and discuss the possible value of the utilized approach.

Original languageEnglish
Pages (from-to)187-201
Number of pages15
JournalNeuroscience and Biobehavioral Reviews
Volume46
Issue numberP2
DOIs
Publication statusPublished - Oct 1 2014

Keywords

  • MeCP2
  • Molecular genetics
  • Pathway enrichment analysis
  • Perturbation in gene expression
  • Rett syndrome
  • Structure and function

ASJC Scopus subject areas

  • Behavioral Neuroscience
  • Cognitive Neuroscience
  • Neuropsychology and Physiological Psychology
  • Medicine(all)

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    Bedogni, F., Rossi, R. L., Galli, F., Cobolli Gigli, C., Gandaglia, A., Kilstrup-Nielsen, C., & Landsberger, N. (2014). Rett syndrome and the urge of novel approaches to study MeCP2 functions and mechanisms of action. Neuroscience and Biobehavioral Reviews, 46(P2), 187-201. https://doi.org/10.1016/j.neubiorev.2014.01.011