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.
- Alzheimer's disease
- APP mRNA 5′untranslated region
- Drug screen
- FDA-2000 Drug library
ASJC Scopus subject areas