Spinal and bulbar muscular atrophy: a motoneuron or muscle disease?

Curr Opin Pharmacol. 2008 Dec;8(6):752-8. doi: 10.1016/j.coph.2008.08.006. Epub 2008 Sep 18.


Kennedy disease (KD, or spinal and bulbar muscular atrophy) is caused by a CAG/polyglutamine expansion in the androgen receptor (AR) gene. Both motoneurons and muscles are affected by KD, but where mutant ARs act to initiate this disease is not clear. We discuss recent insights into this disease with two main themes. (1) KD is androgen-dependent, suggesting that blocking androgen action may be an effective treatment. (2) Androgens may trigger KD by acting in muscles, which indirectly affects the motoneurons, suggesting that blocking AR function in muscles may rescue motoneurons from disease and provide an effective treatment. Future research will provide a better understanding of how androgens trigger KD and the relative contributions of motoneurons versus muscles in this disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bulbo-Spinal Atrophy, X-Linked / genetics
  • Bulbo-Spinal Atrophy, X-Linked / pathology*
  • Bulbo-Spinal Atrophy, X-Linked / physiopathology
  • Humans
  • Models, Biological
  • Motor Neuron Disease / genetics
  • Motor Neuron Disease / pathology*
  • Motor Neuron Disease / physiopathology
  • Muscular Diseases / pathology*
  • Muscular Diseases / physiopathology
  • Mutation
  • Receptors, Androgen / genetics
  • Receptors, Androgen / physiology


  • Receptors, Androgen