微小RNA和RNA结合蛋白对淀粉样前体蛋白的转录后调控
Post-transcriptional regulation of amyloid precursor protein by microRNAs and RNA binding proteins.
作者信息
Ruberti Francesca, Barbato Christian, Cogoni Carlo
机构信息
INMM-CNR Istituto di Neurobiologia e Medicina Molecolare; IRCSS; Fondazione Santa Lucia.
出版信息
Commun Integr Biol. 2010 Nov;3(6):499-503. doi: 10.4161/cib.3.6.13172. Epub 2010 Nov 1.
Abstract
Amyloid Precursor Protein (APP) and its proteolytic product amyloid beta (Aβ) are critical in the pathogenesis of Alzheimer's Disease (AD). APP gene duplication and transcriptional upregulation are linked to AD. In addition, normal levels of APP appear to be required for some physiological functions in the developing brain. Several studies in mammalian cell lines and primary neuron cultures indicate that RNA binding proteins and microRNAs interacting with regulatory regions of the APP mRNA modulate expression of APP post-transcriptionally. However, when the various mechanisms of APP post-transcriptional regulation are recruited and which of them are acting in a synergistic fashion to balance APP protein levels, is unclear. Recent studies suggest that further investigation of the molecules and pathways involved in APP post-transcriptional regulation are warranted.
摘要
淀粉样前体蛋白（APP）及其蛋白水解产物β淀粉样蛋白（Aβ）在阿尔茨海默病（AD）的发病机制中至关重要。APP基因复制和转录上调与AD相关。此外，发育中的大脑的某些生理功能似乎需要正常水平的APP。在哺乳动物细胞系和原代神经元培养物中的多项研究表明，与APP mRNA调控区域相互作用的RNA结合蛋白和微小RNA在转录后调节APP的表达。然而，APP转录后调控的各种机制何时被启用，以及其中哪些机制以协同方式发挥作用来平衡APP蛋白水平，尚不清楚。最近的研究表明，有必要进一步研究参与APP转录后调控的分子和途径。
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