Indoprofen upregulates the survival motor neuron protein through a cyclooxygenase-independent mechanism

Mitchell R. Lunn, David E. Root, Allison M. Martino, Stephen P. Flaherty, Brian P. Kelley, Daniel D. Coovert, Arthur H. Burghes, Nguyen Thi Man, Glenn E. Morris, Jianhua Zhou, Elliot J. Androphy, Charlotte J. Sumner, Brent R. Stockwell

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

Most patients with the pediatric neurodegenerative disease spinal muscular atrophy have a homozygous deletion of the survival motor neuron 1 (SMN1) gene, but retain one or more copies of the closely related SMN2 gene. The SMN2 gene encodes the same protein (SMN) but produces it at a low efficiency compared with the SMN1 gene. We performed a high-throughput screen of ∼47,000 compounds to identify those that increase production of an SMN2-luciferase reporter protein, but not an SMN1-luciferase reporter protein. Indoprofen, a nonsteroidal anti-inflammatory drug (NSAID) and cyclooxygenase (COX) inhibitor, selectively increased SMN2-luciferase reporter protein and endogenous SMN protein and caused a 5-fold increase in the number of nuclear gems in fibroblasts from SMA patients. No other NSAIDs or COX inhibitors tested exhibited this activity.

Original languageEnglish (US)
Pages (from-to)1489-1493
Number of pages5
JournalChemistry and Biology
Volume11
Issue number11
DOIs
StatePublished - Nov 1 2004

Fingerprint

Indoprofen
Motor Neurons
Prostaglandin-Endoperoxide Synthases
Neurons
Up-Regulation
Luciferases
Genes
Cyclooxygenase Inhibitors
Proteins
Survival of Motor Neuron 1 Protein
Spinal Muscular Atrophy
Neurodegenerative diseases
Gems
Non-Steroidal Anti-Inflammatory Agents
Pediatrics
Neurodegenerative Diseases
Fibroblasts
Anti-Inflammatory Agents
Throughput
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

Cite this

Lunn, M. R., Root, D. E., Martino, A. M., Flaherty, S. P., Kelley, B. P., Coovert, D. D., ... Stockwell, B. R. (2004). Indoprofen upregulates the survival motor neuron protein through a cyclooxygenase-independent mechanism. Chemistry and Biology, 11(11), 1489-1493. https://doi.org/10.1016/j.chembiol.2004.08.024

Indoprofen upregulates the survival motor neuron protein through a cyclooxygenase-independent mechanism. / Lunn, Mitchell R.; Root, David E.; Martino, Allison M.; Flaherty, Stephen P.; Kelley, Brian P.; Coovert, Daniel D.; Burghes, Arthur H.; Thi Man, Nguyen; Morris, Glenn E.; Zhou, Jianhua; Androphy, Elliot J.; Sumner, Charlotte J.; Stockwell, Brent R.

In: Chemistry and Biology, Vol. 11, No. 11, 01.11.2004, p. 1489-1493.

Research output: Contribution to journalArticle

Lunn, MR, Root, DE, Martino, AM, Flaherty, SP, Kelley, BP, Coovert, DD, Burghes, AH, Thi Man, N, Morris, GE, Zhou, J, Androphy, EJ, Sumner, CJ & Stockwell, BR 2004, 'Indoprofen upregulates the survival motor neuron protein through a cyclooxygenase-independent mechanism', Chemistry and Biology, vol. 11, no. 11, pp. 1489-1493. https://doi.org/10.1016/j.chembiol.2004.08.024
Lunn, Mitchell R. ; Root, David E. ; Martino, Allison M. ; Flaherty, Stephen P. ; Kelley, Brian P. ; Coovert, Daniel D. ; Burghes, Arthur H. ; Thi Man, Nguyen ; Morris, Glenn E. ; Zhou, Jianhua ; Androphy, Elliot J. ; Sumner, Charlotte J. ; Stockwell, Brent R. / Indoprofen upregulates the survival motor neuron protein through a cyclooxygenase-independent mechanism. In: Chemistry and Biology. 2004 ; Vol. 11, No. 11. pp. 1489-1493.
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