Oct 23, 2017 · Recently an IRE is found in the 5′-UTR of amyloid precursor protein (APP) and α-synuclein (α-Syn) transcripts. The levels of α-Syn, APP and amyloid β-peptide (Aβ) as well as protein aggregation can be down-regulated by IRPs but are up …

The APP IRE is homologous with the canonical IRE RNA stem-loop that binds the iron regulatory proteins (IRP1 and IRP2) to control intracellular iron homoeostasis by modulating ferritin mRNA translation and transferrin receptor mRNA stability.

Dec 11, 2024 · IRP1 binds to the APP IRE with greater affinity as iron levels fall, repressing the translation of the APP protein. The fraction of mRNA in IRE RNA/IRP1 complexes, which prevent ribosome binding, decreases and the fraction of mRNAs in polyribosomes increases when iron concentrations in cells rise.

Mar 28, 2023 · In the interaction between APP mRNA and IRP1, iron promotes structural changes in the APP IRE mRNA∙IRP1 complexes by changing the number of hydrogen bonds and promoting a conformational...

Feb 25, 2019 · APP mRNA translation inhibitors such as the anticholinesterase phenserine, and high throughput screened molecules, selectively inhibited the uniquely folded iron-response element (IRE) sequences in the 5’untranslated region (5’UTR) of APP mRNA and this class of drug continues to be tested in a clinical trial as an anti-amyloid treatment for AD.

Dec 11, 2024 · 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.

Apr 4, 2014 · Iron availability can modulate APP processing, and at high levels inhibits maturation of APP without hindering the formation of immature APP; its chelation reduces APP production . Mechanistically, iron is a pathogenic regulator of both amyloid toxicity and APP translation.

Oct 8, 2010 · Intracellular iron chelation increased binding of IRP1 to the APP IRE, decreasing intracellular APP expression in SH-SY5Y cells. Functionally, shRNA knockdown of IRP1 caused increased expression of neural APP consistent with IRP1-APP IRE-driven translation.

In molecular biology, the iron response element or iron-responsive element (IRE) is a short conserved stem-loop which is bound by iron response proteins (IRPs, also named IRE-BP or IRBP). The IRE is found in UTRs (untranslated regions) of various mRNAs whose products are involved in iron metabolism.

Jul 31, 2013 · Here, we identified thirteen potent APP translation blockers that acted selectively towards the uniquely configured iron-responsive element (IRE) RNA stem loop in the 5′ untranslated region (UTR) of APP mRNA.