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

J. T. Rogers, J. D. Randall, P. S. Eder, X. Huang, A. I. Bush, R. E. Tanzi, A. Venti, S. M. Payton, T. Giordano, S. Nagano, C. M. Cahill, R. Moir, Debomoy Lahiri, N. Greig, S. S. Sarang, S. R. Gullans

Research output: Contribution to journalArticle

46 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)77-82
Number of pages6
JournalJournal of Molecular Neuroscience
Volume19
Issue number1-2
StatePublished - Aug 2002

Fingerprint

Amyloid beta-Protein Precursor
Drug Discovery
Alzheimer Disease
Messenger RNA
Pharmaceutical Preparations
Luciferases
5' Untranslated Regions
Staphylococcal Protein A
Protein Biosynthesis
Chelating Agents
Reporter Genes
Lipid Metabolism
Amyloid
Transfection
Assays
Screening
Genes
Metals
RNA
Anti-Bacterial Agents

Keywords

  • Alzheimer's disease
  • APP mRNA 5′untranslated region
  • Drug screen
  • FDA-2000 Drug library
  • RNA-targeting
  • Translation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry
  • Genetics

Cite this

Rogers, J. T., Randall, J. D., Eder, P. S., Huang, X., Bush, A. I., Tanzi, R. E., ... Gullans, S. R. (2002). Alzheimer's disease drug discovery targeted to the APP mRNA 5′untranslated region. Journal of Molecular Neuroscience, 19(1-2), 77-82.

Alzheimer's disease drug discovery targeted to the APP mRNA 5′untranslated region. / Rogers, J. T.; Randall, J. D.; Eder, P. S.; Huang, X.; Bush, A. I.; Tanzi, R. E.; Venti, A.; Payton, S. M.; Giordano, T.; Nagano, S.; Cahill, C. M.; Moir, R.; Lahiri, Debomoy; Greig, N.; Sarang, S. S.; Gullans, S. R.

In: Journal of Molecular Neuroscience, Vol. 19, No. 1-2, 08.2002, p. 77-82.

Research output: Contribution to journalArticle

Rogers, JT, Randall, JD, Eder, PS, Huang, X, Bush, AI, Tanzi, RE, Venti, A, Payton, SM, Giordano, T, Nagano, S, Cahill, CM, Moir, R, Lahiri, D, Greig, N, Sarang, SS & Gullans, SR 2002, 'Alzheimer's disease drug discovery targeted to the APP mRNA 5′untranslated region', Journal of Molecular Neuroscience, vol. 19, no. 1-2, pp. 77-82.
Rogers JT, Randall JD, Eder PS, Huang X, Bush AI, Tanzi RE et al. Alzheimer's disease drug discovery targeted to the APP mRNA 5′untranslated region. Journal of Molecular Neuroscience. 2002 Aug;19(1-2):77-82.
Rogers, J. T. ; Randall, J. D. ; Eder, P. S. ; Huang, X. ; Bush, A. I. ; Tanzi, R. E. ; Venti, A. ; Payton, S. M. ; Giordano, T. ; Nagano, S. ; Cahill, C. M. ; Moir, R. ; Lahiri, Debomoy ; Greig, N. ; Sarang, S. S. ; Gullans, S. R. / Alzheimer's disease drug discovery targeted to the APP mRNA 5′untranslated region. In: Journal of Molecular Neuroscience. 2002 ; Vol. 19, No. 1-2. pp. 77-82.
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