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

doi:10.1016/j.chembiol.2004.08.024

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 journal › Article › peer-review

120 Scopus citations

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 language	English (US)
Pages (from-to)	1489-1493
Number of pages	5
Journal	Chemistry and Biology
Volume	11
Issue number	11
DOIs	https://doi.org/10.1016/j.chembiol.2004.08.024
State	Published - Nov 2004
Externally published	Yes

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmacology
Drug Discovery
Clinical Biochemistry

Access to Document

10.1016/j.chembiol.2004.08.024

Cite this

Lunn, M. R., Root, D. E., Martino, A. M., Flaherty, S. P., Kelley, B. P., Coovert, D. D., Burghes, A. H., Thi Man, N., Morris, G. E., Zhou, J., Androphy, E. J., Sumner, C. J., & 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

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

@article{9521818f2498429bbba730edfca71c6c,

title = "Indoprofen upregulates the survival motor neuron protein through a cyclooxygenase-independent mechanism",

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.",

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

note = "Funding Information: We thank Jill Heemskerk for valuable suggestions and Harmen Bussemaker for advice on statistical tests. This research was funded by grants from Andrew's Buddies and Families of SMA. B.R.S. is supported in part by a Career Award at the Scientific Interface from the Burroughs Wellcome Fund. ",

year = "2004",

month = nov,

doi = "10.1016/j.chembiol.2004.08.024",

language = "English (US)",

volume = "11",

pages = "1489--1493",

journal = "Chemistry and Biology",

issn = "1074-5521",

publisher = "Elsevier Inc.",

number = "11",

}

TY - JOUR

T1 - Indoprofen upregulates the survival motor neuron protein through a cyclooxygenase-independent mechanism

AU - Lunn, Mitchell R.

AU - Root, David E.

AU - Martino, Allison M.

AU - Flaherty, Stephen P.

AU - Kelley, Brian P.

AU - Coovert, Daniel D.

AU - Burghes, Arthur H.

AU - Thi Man, Nguyen

AU - Morris, Glenn E.

AU - Zhou, Jianhua

AU - Androphy, Elliot J.

AU - Sumner, Charlotte J.

AU - Stockwell, Brent R.

N1 - Funding Information: We thank Jill Heemskerk for valuable suggestions and Harmen Bussemaker for advice on statistical tests. This research was funded by grants from Andrew's Buddies and Families of SMA. B.R.S. is supported in part by a Career Award at the Scientific Interface from the Burroughs Wellcome Fund.

PY - 2004/11

Y1 - 2004/11

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=8844240017&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=8844240017&partnerID=8YFLogxK

U2 - 10.1016/j.chembiol.2004.08.024

DO - 10.1016/j.chembiol.2004.08.024

M3 - Article

C2 - 15555999

AN - SCOPUS:8844240017

SN - 1074-5521

VL - 11

SP - 1489

EP - 1493

JO - Chemistry and Biology

JF - Chemistry and Biology

IS - 11

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this