microRNA 对淀粉样前体蛋白调控的研究进展

淀粉样前体蛋白(APP)参与了神经肌肉的信号传导、突触的可塑性及空间学习等生理过程,APP在阿兹海默病(AD)人脑组织中高表达,其切割产物β淀粉样蛋白(Aβ)则在AD的发生发展中起到重要作用。2011年4月,美国阿兹海默病协会将Aβ的聚集程度列入了新版AD诊疗指南中,通过减少APP的表达或降低其以β切割方式进行代谢来延缓AD的进展已成为很多学者的共识。microRNA(miRNA)是一类内生的、长度约19-24个核苷酸的小RNA,其在细胞内具有多种重要的调节作用,据推测,miRNA调控着人类约三分之一的基因。自2008年首次明确miRNA对APP表达存在调控作用之后,miRNA对APP的调控和相关机制的研究以及其对AD诊断和治疗潜在价值的探索已成为AD研究领域的热点之一,本文主要就miRNA对APP的表达、剪切和切割的调控及Aβ对miRNA的影响做一综述。

Development of the Regulation of microRNA on Amyloid Protein Precursor

The amyloid protein precursor(APP) mediates the nerve-muscle signal transmission,synaptic plasticity and space study physiological processes which are high-expressed in the brain of the Alzheimer’s disease(AD) patients.The fi amyloid protein(Afi),one of the cleaved products of APP,plays an important role in AD events.Afi aggregates degree is listed in the new practice guide-lines of AD by the Alzheimer’s association in April 2011.By reducing the expression of APP or inhibiting its fi cleaving ways to slow the progress of AD has become the consensus of many scholars.MicroRNA(miRNA) is a kind of endogenous small RNA,with around 19-24 nucleotide of length,which has many important regulatory roles.It is supposed that miRNA regulates about one-third of the human gene.Lots of researches focus on the regulative role of miRNA to the APP and its mechanism as well as its value of the diagnosis and treatment to AD since the evidence was found that miRNA can regulate the expression of APP.In this review,we focus on the role of miRNA on the expression,splicing and cleaving of the APP as well as the effect of Afi to the miRNA.