Stress granules as crucibles of ALS pathogenesis

J Cell Biol. 2013 Apr 29;201(3):361-72. doi: 10.1083/jcb.201302044.


Amyotrophic lateral sclerosis (ALS) is a fatal human neurodegenerative disease affecting primarily motor neurons. Two RNA-binding proteins, TDP-43 and FUS, aggregate in the degenerating motor neurons of ALS patients, and mutations in the genes encoding these proteins cause some forms of ALS. TDP-43 and FUS and several related RNA-binding proteins harbor aggregation-promoting prion-like domains that allow them to rapidly self-associate. This property is critical for the formation and dynamics of cellular ribonucleoprotein granules, the crucibles of RNA metabolism and homeostasis. Recent work connecting TDP-43 and FUS to stress granules has suggested how this cellular pathway, which involves protein aggregation as part of its normal function, might be coopted during disease pathogenesis.

Publication types

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

MeSH terms

  • Amyotrophic Lateral Sclerosis / metabolism*
  • Amyotrophic Lateral Sclerosis / pathology
  • Animals
  • Ataxins
  • Cytoplasmic Granules / metabolism*
  • DNA-Binding Proteins / metabolism
  • Environmental Exposure
  • Humans
  • Nerve Tissue Proteins / metabolism
  • Prions / metabolism
  • Protein Structure, Tertiary
  • RNA-Binding Protein FUS / metabolism
  • Stress, Physiological


  • Ataxins
  • DNA-Binding Proteins
  • Nerve Tissue Proteins
  • Prions
  • RNA-Binding Protein FUS