Functional role of caspase-1 and caspase-3 in an ALS transgenic mouse model Academic Article Article uri icon


MeSH Major

  • Biomedical Research
  • Chronic Traumatic Encephalopathy


  • Mutations in the copper/zinc superoxide dismutase (SOD1) gene produce an animal model of familial amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder. To test a new therapeutic strategy for ALS, we examined the effect of caspase inhibition in transgenic mice expressing mutant human SOD1 with a substitution of glycine to alanine in position 93 (mSOD1(G93A)). Intracerebroventricular administration of zVAD-fmk, a broad caspase inhibitor, delays disease onset and mortality. Moreover, zVAD-fmk inhibits caspase-1 activity as well as caspase-1 and caspase-3 mRNA up-regulation, providing evidence for a non-cell-autonomous pathway regulating caspase expression. Caspases play an instrumental role in neurodegeneration in transgenic mSOD1(G93A) mice, which suggests that caspase inhibition may have a protective role in ALS.

publication date

  • April 14, 2000



  • Academic Article


Digital Object Identifier (DOI)

  • 10.1126/science.288.5464.335

PubMed ID

  • 10764647

Additional Document Info

start page

  • 335

end page

  • 9


  • 288


  • 5464