Molecular biology of amyotrophic lateral sclerosis: insights from genetics

Nat Rev Neurosci. 2006 Sep;7(9):710-23. doi: 10.1038/nrn1971.


Amyotrophic lateral sclerosis (ALS) is a paralytic disorder caused by motor neuron degeneration. Mutations in more than 50 human genes cause diverse types of motor neuron pathology. Moreover, defects in five Mendelian genes lead to motor neuron disease, with two mutations reproducing the ALS phenotype. Analyses of these genetic effects have generated new insights into the diverse molecular pathways involved in ALS pathogenesis. Here, we present an overview of the mechanisms for motor neuron death and of the role of non-neuronal cells in ALS.

Publication types

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

MeSH terms

  • Amyotrophic Lateral Sclerosis / genetics*
  • Amyotrophic Lateral Sclerosis / metabolism
  • Amyotrophic Lateral Sclerosis / physiopathology*
  • Animals
  • Apoptosis / genetics
  • Central Nervous System / metabolism
  • Central Nervous System / pathology
  • Central Nervous System / physiopathology*
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Mutation / genetics*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Signal Transduction / genetics
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism
  • Superoxide Dismutase-1


  • Nerve Tissue Proteins
  • SOD1 protein, human
  • Superoxide Dismutase
  • Superoxide Dismutase-1