Selective translational control of the Alzheimer amyloid precursor protein transcript by iron regulatory protein-1

Topic: Amyloid, tau and blood-test diagnosis

Iron influx increases the translation of the Alzheimer amyloid precursor protein (APP) via an iron-responsive element (IRE) RNA stem loop in its 5'-untranslated region. Equal modulated interaction of the iron regulatory proteins (IRP1 and IRP2) with canonical IREs controls iron-dependent translation of the ferritin subunits. However, our immunoprecipitation RT-PCR and RNA binding experiments demonstrated that IRP1, but not IRP2, selectively bound the APP IRE in human neural cells.

@article{cho2010-20558735,
  author  = {Cho, H. H. and Cahill, C. M. and Vanderburg, C. R. and Scherzer, C. R. and Wang, B. and Huang, X. and Rogers, J. T.},
  title   = {{Selective translational control of the Alzheimer amyloid precursor protein transcript by iron regulatory protein-1}},
  journal = {The Journal of biological chemistry},
  year    = {2010},
  doi     = {10.1074/jbc.m110.149161},
  pmid    = {20558735},
  url     = {https://doi.org/10.1074/jbc.m110.149161}
}

Key findings

• Equal modulated interaction of the iron regulatory proteins (IRP1 and IRP2) with canonical IREs controls iron-dependent translation of the ferritin subunits.
• However, our immunoprecipitation RT-PCR and RNA binding experiments demonstrated that IRP1, but not IRP2, selectively bound the APP IRE in human neural cells.
• This selective IRP1 interaction pattern was evident in human brain and blood tissue from normal and Alzheimer disease patients.
• We computer-predicted an optimal novel RNA stem loop structure for the human, rhesus monkey, and mouse APP IREs with reference to the canonical ferritin IREs but also the IREs encoded by erythroid heme biosynthetic aminolevulinate synthase and Hif-2α mRNAs, which preferentially bind IRP1.

Why it matters

In human neural cells, the protein IRP1 selectively bound to a specific RNA structure in the amyloid precursor protein transcript, linking iron regulation to APP production. This is laboratory and tissue-based work on how APP is made, not a demonstrated treatment or prevention strategy.

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Study details

• Evidence strengthLow

Read the original

• DOI: 10.1074/jbc.m110.149161
• PubMed: 20558735
• Original source →
• Free full text: Journal of Biological Chemistry →

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• Metal-protein attenuation with iodochlorhydroxyquin (clioquinol) targeting Abeta amyloid deposition and toxicity in Alzheimer disease: a pilot phase 2 clinical trial Archives of neurology · 2003-12-01 · usefulness score 72/100 · Treatments
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