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

Author

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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)

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.

Suggested Citation

  • Malin K. Sandberg & Huda Al-Doujaily & Bernadette Sharps & Anthony R. Clarke & John Collinge, 2011. "Prion propagation and toxicity in vivo occur in two distinct mechanistic phases," Nature, Nature, vol. 470(7335), pages 540-542, February.
    • Handle: RePEc:nat:nature:v:470:y:2011:i:7335:d:10.1038_nature09768
    DOI: 10.1038/nature09768
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    Cited by:

    1. Christine Rother & Ruth E. Uhlmann & Stephan A. Müller & Juliane Schelle & Angelos Skodras & Ulrike Obermüller & Lisa M. Häsler & Marius Lambert & Frank Baumann & Ying Xu & Carina Bergmann & Giulia Sa, 2022. "Experimental evidence for temporal uncoupling of brain Aβ deposition and neurodegenerative sequelae," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    2. Yan Zhang & Sergio Casas-Tinto & Diego E Rincon-Limas & Pedro Fernandez-Funez, 2014. "Combined Pharmacological Induction of Hsp70 Suppresses Prion Protein Neurotoxicity in Drosophila," PLOS ONE, Public Library of Science, vol. 9(2), pages 1-10, February.

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