Oxidative stress plays an important role in brain aging and neurodegenerative conditions. Genomic DNA is particularly vulnerable to oxidative stress, thus preserving genomic integrity is a key for brain health. Base excision repair (BER) is the major pathway for removal of damaged bases and initiated by DNA glycosylases. Based on our work and others, it appears that processing of oxidized base lesions to avoid DNA mutations is not the sole function of DNA glycosylases. Instead, we propose an epigenetic-like function of oxidative base lesions and DNA glycosylases as modifiers of the epigenetic landscape in brain. 

To uncover novel molecular mechanisms of genome regulation that are important for brain function during health and disease, we are using a multidisciplinary approach combining state-of-the-art human cell reprogramming technologies such as iPSC-brain organoid differentiation and direct neuronal conversion, as well as mouse genetics with next-generation sequencing of the epigenetic and oxidative landscape and functional neuroscience.

Neurodegenerative diseases are characterized by a progressive loss of structure and function of neurons in the central nervous system ultimately resulting in cell death. Common neurodegenerative diseases include Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). To date, no treatment is available to halt or reverse the underlying disease progression and clinical diagnosis is still challenging often only definite after autopsy. 

The Trønderbrain project aims to understand molecular processes that drive the initiation and progression of neurodegenerative diseases with special emphasis on AD. The overall goal is to identify novel biomarkers for early diagnosis and targets for effective therapy.

For more information visit the Trønderbrain homepage here.