Fig. 6.The conjectured mechanism of prion replication. (a) The healthy protein conformation (PrP-sen) is produced at a constant rate, , by the genetic machinery of the host cell. PrP-sen is metabolically degraded at a rate d. (b) PrP-sen monomers are incorporated into aggregates of PrP-res, the diseased form of the prion protein. The change of conformation from PrP-sen to PrP- res is a consequence of aggregation. In the simplest model, aggregates grow at a constant rate, . (c) We assume that PrP-res aggregates can break into smaller pieces, which then form new nuclei for aggregate growth. In this way, the number of PrP-res aggregates increases. (d) PrP-res aggregates are metabolically degraded at rate d, which is thought to be very slow compared to a.