Mitochondria-targeted catalase reverts the neurotoxicity of hSOD1G⁹³A astrocytes without extending the survival of ALS-linked mutant hSOD1 mice.

ABSTRACT: Dominant mutations in the Cu/Zn-superoxide dismutase (SOD1) cause familial forms of amyotrophic lateral sclerosis (ALS), a fatal disorder characterized by the progressive loss of motor neurons. The molecular mechanism underlying the toxic gain-of-function of mutant hSOD1s remains uncertain. Several lines of evidence suggest that toxicity to motor neurons requires damage to non-neuronal cells. In line with this observation, primary astrocytes isolated from mutant hSOD1 over-expressing rodents induce motor neuron death in co-culture. Mitochondrial alterations have been documented in both neuronal and glial cells from ALS patients as well as in ALS-animal models. In addition, mitochondrial dysfunction and increased oxidative stress have been linked to the toxicity of mutant hSOD1 in astrocyte

SUBMITTER: Pehar M 

PROVIDER: S-EPMC4108402 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature