Targeting Iron Responsive Elements (IREs) of APP mRNA into Novel Therapeutics to Control the Translation of Amyloid-β Precursor Protein in Alzheimer's Disease.

The hallmark of Alzheimer's disease (AD) is the buildup of amyloid-β (Aβ), which is produced when the amyloid precursor protein (APP) misfolds and deposits as neurotoxic plaques in the brain. A functional iron responsive element (IRE) RNA stem loop is encoded by the APP 5'-UTR and may be a target for regulating the production of Alzheimer's amyloid precursor protein. Since modifying Aβ protein expression can give anti-amyloid efficacy and protective brain iron balance, targeted regulation of amyloid protein synthesis through modulation of 5'-UTR sequence function is a novel method for the prospective therapy of Alzheimer's disease. Numerous mRNA interference strategies target the 2D RNA structure, even though messenger RNAs like tRNAs and rRNAs can fold into complex, three-dimensional structures, adding even another level of complexity. The IRE family is among the few known 3D mRNA regulatory elements. This review seeks to describe the structural and functional aspects of IREs in transcripts, including that of the amyloid precursor protein, that are relevant to neurodegenerative diseases, including AD. The mRNAs encoding the proteins involved in iron metabolism are controlled by this family of similar base sequences. Like ferritin IRE RNA in their 5'-UTR, iron controls the production of APP in their 5'-UTR. Iron misregulation by iron regulatory proteins (IRPs) can also be investigated and contrasted using measurements of the expression levels of tau production, Aβ, and APP. The development of AD is aided by iron binding to Aβ, which promotes Aβ aggregation. The development of small chemical therapeutics to control IRE-modulated expression of APP is increasingly thought to target messenger RNAs. Thus, IRE-modulated APP expression in AD has important therapeutic implications by targeting mRNA structures.