Molecular mechanisms of spinal muscular atrophy

Research output: Contribution to journalArticle

Abstract

Significant strides have been made during the past decade in the understanding of the molecular mechanisms that lead to the autosomal recessive motor neuron disease spinal muscular atrophy. Genetic studies revealed that spinal muscular atrophy is caused by mutation of the telomeric copy of the survival motor neuron gene (SMN1), with all patients retaining at least one copy of the centromeric form of the gene, SMN2. SMN2 produces reduced amounts of full-length SMN messenger ribonucleic acid because of alterative splicing of SMN2-derived transcripts, a process that is governed by specific cisand trans-acting factors. The resulting insufficient expression level of full-length SMN protein likely causes the disease manifestations of spinal muscular atrophy; however, the mechanism for the selective vulnerability of the motor unit to deficiency of this ubiquitously expressed protein remains unknown. It also remains unclear specifically when and where in the motor unit SMN is required. Despite the remaining questions, progress has been made in developing therapeutic strategies targeted to specific points along the pathogenetic pathway of spinal muscular atrophy. Histone deacetylase inhibitors will be discussed as an example.

Original languageEnglish (US)
Pages (from-to)979-989
Number of pages11
JournalJournal of child neurology
Volume22
Issue number8
DOIs
StatePublished - Aug 1 2007

Keywords

  • Motor neuron
  • Spinal muscular atrophy
  • Survival motor neuron

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Clinical Neurology

Fingerprint Dive into the research topics of 'Molecular mechanisms of spinal muscular atrophy'. Together they form a unique fingerprint.

  • Cite this