Abstract
We performed a screen for drugs that specifically interact with the 5′ untranslated region of the mRNA coding for the Alzheimer’s Amyloid Precursor Protein (APP). Using a transfection based assay, in which APP 5′UTR sequences drive the translation of a downstream luciferase reporter gene, we have been screening for new therapeutic compounds that already have FDA approval and are pharmacologically and clinically well-characterized. Several classes of FDA-pre-approved drugs (16 hits) reduced APP 5′UTR-directed luciferase expression (>95% inhibition of translation). The classes of drugs include known blockers of receptor ligand interactions, bacterial antibiotics, drugs involed in lipid metabolism, and metal chelators. These APP 5′UTR directed drugs exemplify a new strategy to identify RNA-directed agents to lower APP translation and Aβ peptide output for Alzheimer’s disease therapeutics.
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Rogers, J.T., Randall, J.D., Eder, P.S. et al. Alzheimer’s disease drug discovery targeted to the APP mRNA 5′Untranslated region. J Mol Neurosci 19, 77–82 (2002). https://doi.org/10.1007/s12031-002-0014-6
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DOI: https://doi.org/10.1007/s12031-002-0014-6