Functional role of caspase-1 and caspase-3 in an ALS transgenic mouse model - PubMed (original) (raw)
Functional role of caspase-1 and caspase-3 in an ALS transgenic mouse model
M Li et al. Science. 2000.
Abstract
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.
Comment in
- Neurobiology. Stay the executioner's hand.
Gurney ME, Tomasselli AG, Heinrikson RL. Gurney ME, et al. Science. 2000 Apr 14;288(5464):283-4. doi: 10.1126/science.288.5464.283. Science. 2000. PMID: 10777410 No abstract available.
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