Spinal muscular atrophy: a deficiency in a ubiquitous protein; a motor neuron-specific disease

Neuron. 2005 Dec 22;48(6):885-96. doi: 10.1016/j.neuron.2005.12.001.


Spinal muscular atrophy (SMA) is a neurodegenerative disease in humans and the most common genetic cause of infant mortality. The disease results in motor neuron loss and skeletal muscle atrophy. Despite a range of disease phenotypes, SMA is caused by mutations in a single gene, the Survival of Motor Neuron 1 (SMN1) gene. Recent advances have shed light on functions of the protein product of this gene and the pathophysiology of the disease, yet, fundamental questions remain. This review attempts to highlight some of the recent advances made in the understanding of the disease and how loss of the ubiquitously expressed survival of motor neurons (SMN) protein results in the SMA phenotype. Answers to some of the questions raised may ultimately result in a viable treatment for SMA.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cyclic AMP Response Element-Binding Protein / deficiency
  • Cyclic AMP Response Element-Binding Protein / genetics*
  • Humans
  • Inheritance Patterns / genetics
  • Models, Animal
  • Motor Neurons / metabolism*
  • Motor Neurons / pathology
  • Muscular Atrophy, Spinal / genetics*
  • Muscular Atrophy, Spinal / metabolism*
  • Muscular Atrophy, Spinal / physiopathology
  • Mutation / genetics
  • Nerve Degeneration / genetics
  • Nerve Degeneration / metabolism
  • Nerve Tissue Proteins / deficiency
  • Nerve Tissue Proteins / genetics*
  • RNA, Small Nuclear / genetics
  • RNA, Small Nuclear / metabolism
  • RNA-Binding Proteins / genetics*
  • SMN Complex Proteins
  • Spinal Cord / metabolism*
  • Spinal Cord / pathology
  • Spinal Cord / physiopathology
  • Survival of Motor Neuron 1 Protein


  • Cyclic AMP Response Element-Binding Protein
  • Nerve Tissue Proteins
  • RNA, Small Nuclear
  • RNA-Binding Proteins
  • SMN Complex Proteins
  • SMN1 protein, human
  • Survival of Motor Neuron 1 Protein