Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adrenergic beta-Agonists / pharmacology*
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Albuterol / pharmacology*
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Cyclic AMP Response Element-Binding Protein / genetics
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Cyclic AMP Response Element-Binding Protein / metabolism*
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Exons / genetics
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Fibroblasts / drug effects*
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Fibroblasts / metabolism
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Gene Expression Regulation*
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Humans
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Muscular Atrophy, Spinal / drug therapy
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Muscular Atrophy, Spinal / genetics
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Muscular Atrophy, Spinal / metabolism
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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RNA Splicing / drug effects
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RNA, Messenger / genetics
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RNA, Messenger / metabolism*
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RNA-Binding Proteins / genetics
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RNA-Binding Proteins / metabolism*
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SMN Complex Proteins
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Survival of Motor Neuron 1 Protein
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Survival of Motor Neuron 2 Protein
Substances
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Adrenergic beta-Agonists
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Cyclic AMP Response Element-Binding Protein
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Nerve Tissue Proteins
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RNA, Messenger
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RNA-Binding Proteins
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SMN Complex Proteins
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SMN1 protein, human
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SMN2 protein, human
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Survival of Motor Neuron 1 Protein
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Survival of Motor Neuron 2 Protein
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Albuterol