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Indoprofen Upregulates the Survival Motor Neuron Protein through a Cyclooxygenase-Independent Mechanism
- Source :
- Chemistry & Biology. 11:1489-1493
- Publication Year :
- 2004
- Publisher :
- Elsevier BV, 2004.
-
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.
- Subjects :
- Clinical Biochemistry
Drug Evaluation, Preclinical
Nerve Tissue Proteins
Endogeny
SMN1
Biochemistry
Article
Mice
Pregnancy
Drug Discovery
medicine
Animals
Humans
Cyclooxygenase Inhibitors
Cyclic AMP Response Element-Binding Protein
Molecular Biology
Gene
Pharmacology
biology
Anti-Inflammatory Agents, Non-Steroidal
RNA-Binding Proteins
SMN Complex Proteins
Indoprofen
General Medicine
Spinal muscular atrophy
Fibroblasts
Motor neuron
medicine.disease
SMA
Survival of Motor Neuron 1 Protein
Molecular biology
Up-Regulation
nervous system diseases
Survival of Motor Neuron 2 Protein
medicine.anatomical_structure
Prostaglandin-Endoperoxide Synthases
biology.protein
Molecular Medicine
Female
Cyclooxygenase
medicine.drug
Subjects
Details
- ISSN :
- 10745521
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Chemistry & Biology
- Accession number :
- edsair.doi.dedup.....a6be4a4fd2e8d5c0387e6cc123f87892