Chaperone dysfunction in motor neuron disease: new insights from studies of the SMN complex

Genetics. 2025 Mar 17;229(3):iyae223. doi: 10.1093/genetics/iyae223.

Abstract

Spinal muscular atrophy and amyotrophic lateral sclerosis are devastating neurodegenerative diseases characterized by motor neuron loss. Although these 2 disorders have distinct genetic origins, recent studies suggest that they share common etiological mechanisms rooted in proteostatic dysfunction. At the heart of this emerging understanding is the survival motor neuron (SMN) complex.

Keywords: ALS; SMA; SMN; TDP-43; amyotrophic lateral sclerosis; genetic suppressors; heat shock proteins; hspA; spinal muscular atrophy; survival motor neuron.

Publication types

  • Review

MeSH terms

  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / metabolism
  • Animals
  • Humans
  • Molecular Chaperones* / genetics
  • Molecular Chaperones* / metabolism
  • Motor Neuron Disease* / genetics
  • Motor Neuron Disease* / metabolism
  • Motor Neurons / metabolism
  • Muscular Atrophy, Spinal / genetics
  • Muscular Atrophy, Spinal / metabolism
  • SMN Complex Proteins* / genetics
  • SMN Complex Proteins* / metabolism

Substances

  • SMN Complex Proteins
  • Molecular Chaperones