Zheng Fei, Zhou Xianju, Moon Changjong, Wang Hongbing
Department of Biochemistry, St. Jude Children's Research Hospital Memphis, TN38105, USA.
Int J Physiol Pathophysiol Pharmacol. 2012;4(4):188-200. Epub 2012 Dec 26.
Brain-derived neurotrophic factor (BDNF) plays critical roles in many aspects of brain functions, including cell survival, differentiation, development, learning and memory. Aberrant BDNF expression has also been implicated in numerous neurological disorders. Thus, significant effort has been made to understand how BDNF transcription as well as translation is regulated. Interestingly, the BDNF gene structure suggests that multiple promoters control its transcription, leading to the existence of distinct mRNA species. Further, the long- and short-tail of the 3'un-translated region may dictate different sub-cellular BDNF mRNA targeting and translational responses following neuronal stimulation. This review aims to summarize the main findings that demonstrate how neuronal activities specifically up-regulate the transcription and translation of unique BDNF transcripts. We also discuss some of the recent reports that emphasize the epigenetic regulation of BDNF transcription.
脑源性神经营养因子(BDNF)在脑功能的许多方面发挥着关键作用,包括细胞存活、分化、发育、学习和记忆。BDNF表达异常也与多种神经疾病有关。因此,人们已付出巨大努力来了解BDNF转录及翻译是如何被调控的。有趣的是,BDNF基因结构表明多个启动子控制其转录,导致存在不同的mRNA种类。此外,3'非翻译区的长尾巴和短尾巴可能决定神经元刺激后不同的亚细胞BDNF mRNA靶向和翻译反应。本综述旨在总结主要研究结果,这些结果证明了神经元活动如何特异性地上调独特BDNF转录本的转录和翻译。我们还讨论了一些强调BDNF转录表观遗传调控的最新报道。