Prion propagation and toxicity in vivo occur in two distinct mechanistic phases

Malin K. Sandberg, Huda Al-Doujaily, Bernadette Sharps, Anthony R. Clarke and John Collinge ()
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Malin K. Sandberg: UCL Institute of Neurology, Queen Square
Huda Al-Doujaily: UCL Institute of Neurology, Queen Square
Bernadette Sharps: UCL Institute of Neurology, Queen Square
Anthony R. Clarke: UCL Institute of Neurology, Queen Square
John Collinge: UCL Institute of Neurology, Queen Square

Nature, 2011, vol. 470, issue 7335, 540-542

Abstract: Two-stage prion infection 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.

Date: 2011
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DOI: 10.1038/nature09768

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