Knockout of reactive astrocyte activating factors slows disease progression in an ALS mouse model

Nat Commun. 2020 Jul 27;11(1):3753. doi: 10.1038/s41467-020-17514-9.


Reactive astrocytes have been implicated in the pathogenesis of neurodegenerative diseases, including a non-cell autonomous effect on motor neuron survival in ALS. We previously defined a mechanism by which microglia release three factors, IL-1α, TNFα, and C1q, to induce neurotoxic astrocytes. Here we report that knocking out these three factors markedly extends survival in the SOD1G93A ALS mouse model, providing evidence for gliosis as a potential ALS therapeutic target.

Publication types

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

MeSH terms

  • Amyotrophic Lateral Sclerosis / metabolism*
  • Amyotrophic Lateral Sclerosis / pathology*
  • Animals
  • Astrocytes / metabolism*
  • Complement C1q / metabolism*
  • Complement C3 / metabolism
  • Disease Models, Animal
  • Disease Progression*
  • Humans
  • Interleukin-1alpha / metabolism*
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microglia
  • Superoxide Dismutase-1 / metabolism
  • Tumor Necrosis Factor-alpha / metabolism*


  • Complement C3
  • Interleukin-1alpha
  • Tumor Necrosis Factor-alpha
  • Complement C1q
  • Superoxide Dismutase-1