Abstract
Prions are infectious proteins that can cause deadly diseases in mammals. Detailed measurements of infectivity suggest that there may be distinct infectious and toxic versions of this protein. See Letter p.540 Prion infections have a clinically silent incubation period that can go on for years or even decades, followed by an aggressive, short clinical phase. Experiments in the RML mouse model of prion disease now show that prion propagation in the brain proceeds by two distinct phases: a relatively brief exponential phase that is not rate-limited by prion protein concentration, followed by a plateau phase. Surprisingly, it is the latter that can be very prolonged, accounting for the majority of the clinically silent incubation period. The similar levels of infectivity at the end of the first and second phase suggest that there is a separation between prion infectivity and toxicity. The authors suggest that the prions are not neurotoxic themselves, but catalyse the formation of such species from host-cell-encoded cellular prion protein.
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