BDNF deregulation in Rett syndrome

NEUROPHARMACOLOGY

卷:76

Review

Li, Wei¹  Pozzo-Miller, Lucas¹ 

[1] Univ Alabama Birmingham, Dept Neurobiol, Civitan Int Res Ctr, Birmingham, AL 35294 USA

关键词: BDNF;    MeCP2;    Rett syndrome;    Intellectual disability;    Mouse models;   

DOI  :  10.1016/j.neuropharm.2013.03.024

来源: Elsevier

【 摘 要 】

BDNF is the best-characterized neurotrophin in terms of its gene structure and modulation, secretion processing, and signaling cascades following its release. In addition to diverse features at the genetic and molecular levels, the abundant expression in several regions of the central nervous system has implicated BDNF as a potent modulator in many aspects of neuronal development, as well as synaptic transmission and plasticity. Impairments in any of these critical functions likely contribute to a wide array of neurodevelopmental, neurodegenerative, and neuropsychiatric diseases. In this review, we focus on a prevalent neurodevelopmental disorder, Rett syndrome (121T), which afflicts 1:15,000 women world-wide. We describe the consequences of loss-of-function mutations in the gene encoding the transcription factor methyl-CpG binding protein 2 (MeCP2) in WIT, and then elaborate on the current understanding of how MeCP2 controls BDNF expression. Finally, we discuss the literature regarding alterations in BDNF levels in RU individuals and MeCP2-based mouse models, as well as recent progress in searching for rational therapeutic interventions. This article is part of the Special Issue entitled 'BDNF Regulation of Synaptic Structure, Function, and Plasticity'. (C) 2013 Elsevier Ltd. All rights reserved.

【 授权许可】

Free