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Updated: Jun 10, 2026
Protein Misfolding Cyclic Amplification of Prions
Published on: November 7, 2012
Spontaneous generation of mammalian prions
Julie A Edgeworth1, Nathalie Gros, Jack Alden
1Medical Research Council Prion Unit, Department of Neurodegenerative Disease, University College London Institute of Neurology, London WC1N 3BG, United Kingdom.
Abstract:
Prions are transmissible agents that cause lethal neurodegeneration in humans and other mammals. Prions bind avidly to metal surfaces such as steel wires and, when surface-bound, can initiate infection of brain or cultured cells with remarkable efficiency. While investigating the properties of metal-bound prions by using the scrapie cell assay to measure infectivity, we observed, at low frequency, positive assay results in control groups in which metal wires had been coated with uninfected mouse brain homogenate. This phenomenon proved to be reproducible in rigorous and exhaustive control experiments designed to exclude prion contamination. The infectivity generated in cell culture could be readily transferred to mice and had strain characteristics distinct from the mouse-adapted prion strains used in the laboratory. The apparent "spontaneous generation" of prions from normal brain tissue could result if the metal surface, possibly with bound cofactors, catalyzed de novo formation of prions from normal cellular prion protein. Alternatively, if prions were naturally present in the brain at levels not detectable by conventional methods, metal surfaces might concentrate them to the extent that they become quantifiable by the scrapie cell assay.
Insights
Researchers observed the apparent spontaneous generation of prions from normal brain tissue on metal surfaces. This unexpected finding suggests metal may catalyze prion formation or concentrate undetectable prions.
Area of Science:
- Neuroscience
- Biochemistry
- Infectious Diseases
Background:
- Prions are infectious proteins causing fatal neurodegenerative diseases.
- Prions bind strongly to metal surfaces, increasing their infectious potential.
- The scrapie cell assay is used to measure prion infectivity.
Purpose of the Study:
- To investigate the properties of metal-bound prions.
- To understand the mechanism behind prion infectivity on metal surfaces.
- To explore the possibility of de novo prion formation.
Main Methods:
- Utilizing the scrapie cell assay to measure prion infectivity.
- Conducting rigorous control experiments with uninfected brain homogenate on metal wires.
- Transferring generated infectivity to mice for further analysis.
Main Results:
- Observed unexpected positive prion infectivity in control groups using uninfected brain homogenate on metal wires.
- Reproducible generation of infectivity in cell culture, transferable to mice.
- Generated prions exhibited distinct strain characteristics.
Conclusions:
- Metal surfaces may catalyze the de novo formation of prions from normal cellular prion protein, potentially involving cofactors.
- Alternatively, metal surfaces might concentrate naturally occurring, yet undetectable, prions to quantifiable levels.
- These findings challenge current understanding of prion pathogenesis and have implications for prion detection and decontamination.
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