Susanne Krasemann

Misfolding and aggregation of endogenous proteins is a common hallmark of several neurodegenerative diseases. The aggregated proteins accumulate, leading to neuronal dysfunction and eventually to neuronal cell death. My research is addressing to aspects in the misfolding cascade in neurodegenerative diseases:

Misfolded proteins do not distribute evenly in the diseased brain. Instead, misfolding starts in distinct areas of the brain and only during the course of disease, start to traffic to distant brain regions. It is currently not known, how the misfolded proteins spread within the brain. Moreover, it is still unclear, if certain conformers or aggregation subtypes eg oligomeric protein species, facilitate the spreading. We are investigating these processes in the prion disease model, where the endogenous prion protein PrP^C misfolds into the disease associated protein isoform PrP^Sc. Using well established cell culture and mouse models, we are able to address different questions in the transport chain of prion proteins.

Microglia cells are the endogenous immune cells of the brain. They react on invading pathogens but also on endogenous misfolded proteins and are principally able to degrade a wide variety of danger associate molecules. However, in the course of neurodegenerative diseases, they lose their potential to clear misfolded protein species from the brain and get pro-inflammatory. Moreover, they might be actively engaged in neuronal loss, since they acquire neurotoxic properties. It is not clear, how this phenotype switch with the loss of homeostatic function is executed on the molecular level. Therefore, my main interest is to identify key proteins in the regulation of microglia cell function. Since microglia cells are also activated in the course of prion diseases, they pose a very good model to study dysregulation of microglia. In this project part, I established a tight collaboration with the group of Prof. Oleg Butovsky (Ann Romney Center for Neurologic Diseases, Harvard Medical School, Boston, USA)