Replication of infectious amyloid in the mammalian cytosol
Prion diseases are neurodegenerative diseases that are caused by uncoventional agents composed mainly if not entirely of an infectious aggregated isoform of the host encoded prion protein PrP. The so called prions replicate by recruitment and conversion of soluble PrP into infectious aggregates. The mechanism of seeded polymerization into ordered protein aggregates is shared by amyloidogenic proteins associated with other neurodegenerative diseases, yet infectivity appears to be a unique feature of prions. The difference between infectious and non infectious amyloid is obscure. It has been proposed that attachment of the prion protein to the outer leaflet of the cell membrane by a glycosylphosphatidyl inositol moiety facilitates spreading of prions from cell to cell. We could recently show that also protein aggregates in the mammalian cytosol can propagate in a self-templating manner with phenotypical and biochemical characteristics typical of prion strains. Importantly, these protein aggregates behave as infectious agents capable of invading and infecting neighboring cells. Our data provide evidence that some cytosolic protein aggregates can faithfully replicate the cellular prion life cycle, arguing that prion-like propagation in mammalian cells does not depend on membrane anchoring and is not restricted to PrP.
HZI Braunschweig, Forum X0.13
Prof. Dr. Ina Vorberg, Prion Cell Biology, DZNE e.V., Bonn
Dr. Thorsten Lührs, Head of Junior Research Group Structure-based Infection Biology, Helmholtz Centre for Infection Research