Journal article

Alzheimer's disease drug discovery targeted to the APP mRNA 5 ' untranslated region

JT Rogers, JD Randall, PS Eder, XD Huang, AI Bush, RE Tanzi, A Venti, SM Payton, T Giordano, S Nagano, CM Cahill, R Moir, DK Lahiri, N Greig, SS Sarang, SR Gullans

JOURNAL OF MOLECULAR NEUROSCIENCE | HUMANA PRESS INC | Published : 2002

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 involved in lipid metab..

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University of Melbourne Researchers