University of Wisconsin, Waisman Center for Developmental Disabilities, 1500 Highland Avenue, Madison, WI 53705, USA.
Ageing Res Rev. 2012 Sep;11(4):450-9. doi: 10.1016/j.arr.2012.03.005. Epub 2012 Apr 5.
Amyloid β-protein precursor (AβPP) is cleaved by β- and γ-secretases to liberate amyloid beta (Aβ), the predominant protein found in the senile plaques associated with Alzheimer's disease (AD) and Down syndrome (Masters et al., 1985). Intense investigation by the scientific community has centered on understanding the molecular pathways that underlie the production and accumulation of Aβ Therapeutics that reduce the levels of this tenacious, plaque-promoting peptide may reduce the ongoing neural dysfunction and neuronal degeneration that occurs so profoundly in AD. AβPP and Aβ production are highly complex and involve still to be elucidated combinations of transcriptional, post-transcriptional, translational and post-translational events that mediate the production, processing and clearance of these proteins. Research in our laboratory for the past two decades has focused on the role of RNA binding proteins (RBPs) in mediating the post-transcriptional as well as translational regulation of APP messenger RNA (mRNA). This review article summarizes our findings, as well as those from other laboratories, describing the identification of regulatory RBPs, where and under what conditions they interact with APP mRNA and how those interactions control AβPP and Aβ synthesis.
淀粉样蛋白 β 前体 (AβPP) 可被 β-和 γ-分泌酶切割，释放出淀粉样 β (Aβ)，这是与阿尔茨海默病 (AD) 和唐氏综合征 (Down 综合征) 相关的老年斑中主要的蛋白 (Masters 等人，1985 年)。科学界的深入研究集中在理解产生和积累 Aβ 的分子途径上。降低这种顽强的、促进斑块形成的肽水平的治疗方法可能会减少 AD 中发生的持续的神经功能障碍和神经元退化。AβPP 和 Aβ 的产生非常复杂，涉及尚未阐明的转录、转录后、翻译和翻译后事件的组合，这些事件介导这些蛋白的产生、加工和清除。我们实验室过去二十年的研究集中在 RNA 结合蛋白 (RBPs) 在调节 APP 信使 RNA (mRNA) 的转录后和翻译水平上的作用。这篇综述文章总结了我们的发现，以及其他实验室的发现，描述了调节性 RBPs 的鉴定，它们在何处以及在何种条件下与 APP mRNA 相互作用，以及这些相互作用如何控制 AβPP 和 Aβ 的合成。
