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

Overview

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.

publication date

  • April 14, 2000

Research

keywords

  • Amino Acid Chloromethyl Ketones
  • Amyotrophic Lateral Sclerosis
  • Caspase 1
  • Caspases
  • Motor Neurons
  • Neuroprotective Agents

Identity

Scopus Document Identifier

  • 0034647003

Digital Object Identifier (DOI)

  • 10.1126/science.288.5464.335

PubMed ID

  • 10764647

Additional Document Info

volume

  • 288

issue

  • 5464