Reducing mitochondrial ROS improves disease-related pathology in a mouse model of ataxia-telangiectasia.

ABSTRACT: The disease ataxia-telangiectasia (A-T) has no cure and few treatment options. It is caused by mutations in the ATM kinase, which functions in the DNA-damage response and redox sensing. In addition to severe cerebellar degeneration, A-T pathology includes cancer predisposition, sterility, immune system dysfunction, and bone marrow abnormalities. These latter phenotypes are recapitulated in the ATM null (ATM(-/-)) mouse model of the disease. Since oxidative stress and mitochondrial dysfunction are implicated in A-T, we determined whether reducing mitochondrial reactive oxygen species (ROS) via overexpression of catalase targeted to mitochondria (mCAT) alleviates A-T-related pathology in ATM(-/-) mice. We found that mCAT has many beneficial effects in this context, including reduced propensi

SUBMITTER: D'Souza AD 

PROVIDER: S-EPMC3538311 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature