Impact of oxidative base lesion repair on Alzheimer's disease
Accumulation of oxidative DNA damage is one causative factor of aging and associated with neurodegenerative diseases such as Alzheimer’s disease (AD). Thus, preserving DNA integrity is essential to maintain neuronal longevity and cognitive functions. Base excision repair is the major pathway to repair oxidative DNA damage, and initiated by DNA glycosylases. Neil3 and Ogg1 DNA glycosylases have been shown to be important for neuroprotection, cognitive function and neurodegenrative diseases but the underlying molecular mechanism is unknown.
We have used a well established mouse model of AD (APP/PS1) to generate novel Neil3 and Ogg1 deficient AD mice. So far no severe phenotype has been observed in these KO mouse models. We would like to use APP/PS1, APP/PS1xNeil3, APP/PS1xOgg1 to further study the role of impaired oxidative base lesion repair in the development of AD with the major focus to discover novel molecular targets for future therapeutic approaches.
To date it is not possible to study all aspects of AD in vitro, in particular cognitive function without the use of appropiate animal models. This application is for breeding and behavior testing only, thus no adverse effects are expected. All our experiments are well planned to avoid an excess use of animals. Mice, which are used for breeding, will be included in the experiments for the later time point to reduce the total amount of mice needed for the analyses. In addition, our study will include both gender to keep the total number of mice at a minimum. We apply for 600 animals over 4 years.
We have used a well established mouse model of AD (APP/PS1) to generate novel Neil3 and Ogg1 deficient AD mice. So far no severe phenotype has been observed in these KO mouse models. We would like to use APP/PS1, APP/PS1xNeil3, APP/PS1xOgg1 to further study the role of impaired oxidative base lesion repair in the development of AD with the major focus to discover novel molecular targets for future therapeutic approaches.
To date it is not possible to study all aspects of AD in vitro, in particular cognitive function without the use of appropiate animal models. This application is for breeding and behavior testing only, thus no adverse effects are expected. All our experiments are well planned to avoid an excess use of animals. Mice, which are used for breeding, will be included in the experiments for the later time point to reduce the total amount of mice needed for the analyses. In addition, our study will include both gender to keep the total number of mice at a minimum. We apply for 600 animals over 4 years.