Membrane anchor suppresses protein aggregation

Hereditary and infectious forms of the disease

Prion diseases are fatal degenerative diseases of the brain. They are associated with the transformation of the cellular prion protein (PrP^C) from its healthy fold into pathological aggregates, i.e. scrapie prion protein (PrP^Sc). While such diseases are rare in humans, hereditary prion diseases are triggered by genetic mutations. Some gene mutations affect the anchoring of PrP^C to the cell membrane. However, it is still not fully understood exactly how these changes can trigger prion diseases.

In order to gain new insights into the underlying processes, the researchers have developed new models to explore the role of a membrane anchor on the folding and aggregation of PrP in vitro and in neuronal cells. The experiments showed that anchoring to membranes stabilizes the folding of PrP and effectively inhibits aggregation. “What’s interesting is that the clumping of membrane-anchored PrP could be induced by pre-formed protein aggregates,” says Jörg Tatzelt. “This is a mechanism that might play a role in infectious prion diseases.”