Iron-responsive element in the 5'-untranslated region of Amyloid Precursor Protein mRNA (APP 5'-UTR IRE)

The iron-responsive element (IRE) in the 5'-untranslated region (UTR) of the Amyloid Precursor Protein (APP) mRNA is a specialized RNA stem-loop structure that controls the rate of APP protein synthesis based on cellular iron availability (Rogers et al., 2002, J Biol Chem). In the presence of low intracellular iron, Iron Regulatory Proteins (IRP1 and IRP2) bind to this IRE, physically blocking the translation machinery from initiating protein synthesis. When iron levels are high, IRPs dissociate, permitting the translation of APP, which has been linked to iron export and neuronal homeostasis (Cho et al., 2010, J Biol Chem). Dysregulation of this system can lead to the overproduction of APP, a precursor to the amyloid-beta (Aβ) peptides that aggregate into plaques in Alzheimer's disease (Bandyopadhyay et al., 2013, Gene). Therapeutic strategies involve using small molecules, such as Posiphen, which bind to or stabilize the IRE-IRP interaction to downregulate APP translation (Muckenthaler et al., 2008, Cell). This approach aims to reduce the total burden of Aβ in the brain by limiting the production of its precursor at the translational level rather than inhibiting the secretase enzymes responsible for its cleavage.

Other names

APP IREAmyloid precursor protein iron-responsive element5'-UTR IRE of APPAPP 5'-untranslated region iron-responsive element

Small molecule binding to the 5'-UTR IRE of APP mRNA to inhibit translation and reduce the production of Amyloid Precursor Protein.