Abstract

The hereditary neurodegenerative disease spinal muscular atrophy (SMA) with childhood onset is one of the most common genetic causes of infant mortality. The disease is characterized by selective loss of spinal cord motor neurons leading to muscle atrophy and is the result of mutations in the survival motor neuron (SMN) gene. The SMN protein has been implicated in diverse nuclear processes including splicing, ribosome formation and gene transcription. Even though the genetic basis of SMA is well understood, it is not clear how defects in these ubiquitous processes result in motor neuron degeneration leaving other tissues unaffected. Recent evidence from animal and cell culture models of SMA points to roles for SMN in neurite outgrowth and axonal transport. Disruption of these functions might be particularly detrimental to motor neurons given their high metabolic demands and precise connectivity requirements, thus providing a possible explanation for the specificity of motor neuron susceptibility in SMA. Understanding the molecular mechanisms of SMN activity in neuronal processes may generate new targets for future therapeutic strategies. BioEssays 27:946–957, 2005. © 2005 Wiley Periodicals, Inc.