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