Effects of oxidative DNA repair deficiency on mitochondrial function in mouse models of Alzheimer's disease

Oxidative damage and mitochondrial dysfunction are common and early events in the pathogenesis of Alzheimer's disease (AD). High levels of mitochondrial DNA damage are present in AD brains and inefficient DNA repair may therefore contribute to AD progression. The DNA glycosylases OGG1, and NEIL3 are important enzymes for the repair of oxidative-damaged DNA and have been shown to function inside mitochondria. We want to establish new mouse models of AD with a deficiency of either OGG1 and NEIL3 alone or a combined knock out of OGG1 and NEIL3 and investigate the effect on mitochondrial function and AD pathology.