role of prion protein membrane-anchoring in transmission and spreading of prion disease
Markus Glatzel and Dmitri Svergun
Illustration: hegasy.de | © Infectophysics 2019
Many fatal neurodegenerative deceases are caused by a misfolded and aggregated form of prion protein, but the cell-to-cell transmission and spreading of these diseases remain elusive. This project will deal with unravelling the molecular and structural mechanisms of how do infectious prion proteins damage the brain. It is known that attachment of prions to membranes and cell-derived vesicles called exosomes plays an important role in the prion fibrillation and in formation of neurotoxic oligomeric species. We shall comprehensively characterize the process of prion aggregation in the presence and absence of exosomes in real time utilizing most novel developments in high brilliance synchrotron X-ray scattering. The scattering studies will be able to detect and identify the transient oligomeric intermediates during prion aggregation, and the structural results will be correlated with the neurotoxicity assays. The results will help understanding potential intracellular protective mechanisms against neurodegenerative diseases.