MeCP2 and Rett syndrome: reversibility and potential avenues for therapy

作者: Kamal K.E. Gadalla , Mark E.S. Bailey , Stuart R. Cobb

DOI: 10.1042/BJ20110648

关键词:

摘要: Mutations in the X-linked gene MECP2 (methyl CpG-binding protein 2) are primary cause of neurodevelopmental disorder RTT (Rett syndrome), and also implicated other neurological conditions. The expression product this gene, MeCP2, is a widely expressed nuclear protein, especially abundant mature neurons CNS (central nervous system). major recognized consequences mutation occur CNS, but there growing awareness peripheral effects contributing to full phenotype. MeCP2 classically considered act as DNA methylation-dependent transcriptional repressor, may have additional roles regulating chromatin structure. Knocking out Mecp2 function mice recapitulates many overt features seen patients, characteristic postnatally delayed onset symptoms accompanied by aberrant neuronal morphology deficits synaptic physiology. Evidence that reactivation endogenous mutant mice, even at adult stages, can reverse aspects RTT-like pathology result apparently functionally has provided renewed hope for provoked discussion about traditional boundaries between disorders those involving dysfunction later stages. In present paper we review neurobiology consider various genetic (including therapy), pharmacological environmental interventions been, could be, developed attempt phenotypic rescue RTT. Such approaches already providing valuable insights into potential tractability related conditions, useful pointers development future therapeutic strategies.

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