Brief Communication Indoprofen Upregulates the Survival Motor Neuron Protein through a Cyclooxygenase-Independent Mechanism

Summary stably expressing an SMN -minigene with luciferase re-porter [13] that consisted of exons 6 through 8 and Most patients with the pediatric neurodegenerative intervening introns, for either SMN1 or SMN2 . Lucifer- disease spinal muscular atrophy have a homozygous ase, the reporter gene’s product, is only produced when deletion of the survival motor neuron 1 ( SMN1 ) gene, proper splicing and translation occurs. but retain one or more copies of the closely related We tested 20,000 compounds from a combinatorial SMN2 gene.The SMN2 geneencodesthesameprotein library, 1040 compounds from a National Institute of (SMN) but produces it at a low efficiency compared Neurological Disorders and Stroke (NINDS) library, 2337 with the SMN1 gene. We performed a high-throughput compoundsfromourAnnotatedCompoundLibrary[14], screen of 47,000 compounds to identify those that and 23,685 compounds from our TIC Library, which is increase production of an SMN2 -luciferase reporter a composite of compounds purchased from TimTec,