Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8260576 | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease | 2013 | 11 Pages |
Abstract
Humans have two nearly identical copies of survival motor neuron gene: SMN1 and SMN2. Deletion or mutation of SMN1 combined with the inability of SMN2 to compensate for the loss of SMN1 results in spinal muscular atrophy (SMA), a leading genetic cause of infant mortality. SMA affects 1 in ~Â 6000 live births, a frequency much higher than in several genetic diseases. The major known defect of SMN2 is the predominant exon 7 skipping that leads to production of a truncated protein (SMNÎ7), which is unstable. Therefore, SMA has emerged as a model genetic disorder in which almost the entire disease population could be linked to the aberrant splicing of a single exon (i.e. SMN2 exon 7). Diverse treatment strategies aimed at improving the function of SMN2 have been envisioned. These strategies include, but are not limited to, manipulation of transcription, correction of aberrant splicing and stabilization of mRNA, SMN and SMNÎ7. This review summarizes up to date progress and promise of various in vivo studies reported for the treatment of SMA.
Keywords
TSAN-methyl d-aspartic acidscAAVFDAsnRNPSTAT5VPAhnRNP A1SAHAGSK-3NMDAintracerebroventricularICVSMNIGF-1CREBNSAIDASOHDACJanus kinaseantisense oligonucleotideTia1spinal muscular atrophyamyotrophic lateral sclerosisSuberoylanilide hydroxamic acidALSTrichostatin AintraperitonealIntravascularSMAsmall nuclear ribonucleoproteinsubcutaneousFood and Drug AdministrationBBBblood brain barrierNon-steroidal anti-inflammatory druginsulin-like growth factor 1signal transducer and activator of transcription 5survival motor neuronhistone deacetylaseValproic acidcyclic AMP response element binding proteinSplicingJAKglycogen synthase kinase 3
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Authors
Joonbae Seo, Matthew D. Howell, Natalia N. Singh, Ravindra N. Singh,