Journal of Medical Genetics · 2007 · 89 citations · 21 references
MedicineNeurologyNeuroscienceGene ExpressionMolecular NeuroscienceNeuromuscular DisordersMotor Neuron DiseasesMuscle PathologyNeurodegenerative DiseasesNeurodegenerative DisordersProtein SynthesisSpinal Muscular AtrophyBeta2-adrenergic Agonist TherapyHomozygous DeletionMotor Neuron FunctionProtein Expression LevelsSmn2 Copy Number VariationSpinal Muscular Atrophy PharmacotherapySurvival Motor Neuron Protein DeficiencyTranscripts
Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder caused by homozygous absence of the survival motor neuron gene (SMN1). All patients have at least one, usually two to four copies of the related SMN2 gene which, however, produce insufficient levels of functional SMN protein due to the exclusion of exon 7 in the majority of SMN2 transcripts. Here, we show that salbutamol, a beta2-adrenoceptor agonist, determines a rapid and significant increase in SMN2-full length mRNA and SMN protein in SMA fibroblasts, predominantly by promoting exon 7 inclusion in SMN2 transcripts. These data, together with previous clinical findings, provide a strong rationale to investigate further the clinical efficacy of salbutamol in SMA patients.
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