Khan Mateen A
Department of Life Science, College of Science and General Studies, Alfaisal University, Riyadh, Saudi Arabia.
Front Aging Neurosci. 2025 May 14;17:1483913. doi: 10.3389/fnagi.2025.1483913. eCollection 2025.
Iron responsive element (IREs) mRNA and iron regulatory proteins (IRPs) regulate iron homeostasis. 5'-untranslated region motifs of APP IREs fold into RNA stem loops bind to IRP to control translation. Through the 5'-UTR APP IREs, iron overload accelerated the translation of the Alzheimer's amyloid precursor protein (APP). The protein synthesis activator eIF4F and the protein synthesis repressor IRP1 are the two types of proteins that IREs bind. Iron regulates the competitive binding of eIF4F and IRP1 to IRE. Iron causes the IRE and eIF4F to associate with one other, causing the dissociation of IRPs and altered translation. In order to control IRE-modulated expression of APP, messenger RNAs are becoming attractive targets for the development of small molecule therapeutics. Many mRNA interference strategies target the 2-D RNA structure, but messenger RNAs like rRNAs and tRNAs can fold into complicated, three-dimensional structures that add another level of complexity. IREs family is one of the few known 3-D mRNA regulatory elements. In this review, I present IREs structural and functional characteristics. For iron metabolism, the mRNAs encoding the proteins are controlled by this family of similar base sequences. Iron has a similar way of controlling the expression of Alzheimer's APP as ferritin IRE RNA in their 5ÚTR. Further, iron mis regulation by IRPs can be investigated and contrasted using measurements of expression levels of APP, amyloid- and tau formation. Accordingly, IRE-modulated APP expression in Alzheimer's disease has great therapeutic potential through targeting mRNA structures.
铁反应元件（IREs）mRNA和铁调节蛋白（IRPs）调节铁稳态。APP IREs的5'-非翻译区基序折叠成RNA茎环与IRP结合以控制翻译。通过5'-UTR APP IREs，铁过载加速了阿尔茨海默病淀粉样前体蛋白（APP）的翻译。蛋白质合成激活剂eIF4F和蛋白质合成抑制剂IRP1是IREs结合的两种蛋白质类型。铁调节eIF4F和IRP1与IRE的竞争性结合。铁使IRE与eIF4F相互结合，导致IRPs解离并改变翻译。为了控制IRE调节的APP表达，信使RNA正成为小分子治疗药物开发的有吸引力的靶点。许多mRNA干扰策略靶向二维RNA结构，但像rRNAs和tRNAs这样的信使RNA可以折叠成复杂的三维结构，增加了另一层复杂性。IREs家族是少数已知的三维mRNA调节元件之一。在这篇综述中，我介绍了IREs的结构和功能特征。对于铁代谢，编码这些蛋白质的mRNA受这一具有相似碱基序列的家族控制。在其5'UTR中，铁对阿尔茨海默病APP表达的控制方式与铁蛋白IRE RNA相似。此外，通过测量APP的表达水平、淀粉样蛋白和tau蛋白的形成，可以研究和对比IRPs对铁的错误调节。因此，通过靶向mRNA结构，IRE调节的APP在阿尔茨海默病中的表达具有巨大的治疗潜力。
