Integrated role of desferrioxamine and phenserine targeted to an iron-responsive element in the APP-mRNA 5′-untranslated region

Abstract

The Alzheimer's amyloid precursor protein (APP) is the metalloprotein that is cleaved to generate the pathogenic Aβ peptide. We showed that iron closely regulated the expression of APP by 5′-untranslated region (5′-UTR) sequences in APP mRNA. Iron modulated APP holoprotein expression by a pathway similar to iron control of the translation of the ferritin-L and -H mRNAs by iron-responsive elements in their 5′-UTRs. APP gene transcription is also responsive to copper deficit where the Menkes protein depleted fibroblasts of copper to suppress transcription of APP through metal regulatory and copper regulatory sequences upstream of the APP 5′ cap site. APP is a copperzinc metalloprotein and chel..