The dynamics of prion spreading is governed by the interplay between the non-linearities of tissue response and replication kinetics.

Prion diseases, or transmissible spongiform encephalopathies (TSEs), are neurodegenerative disorders caused by the accumulation of misfolded conformers (PrP) of the cellular prion protein (PrP). During the pathogenesis, the PrP seeds disseminate in the central nervous system and convert PrP leading to the formation of insoluble assemblies. As for conventional infectious diseases, variations in the clinical manifestation define a specific prion strain which correspond to different PrP structures.

PMCA to demonstrate the efficacy of prion inactivation methods on reusable medical devices: a relevant alternative to animal bioassays.

Validation of prion inactivation processes for medical devices relies on in-vivo experimental protocols. However, bioassays are costly, long (1-2 years) and ethically disputable. Additionally, results obtained with one prion strain - for example, 263K (hamster-adapted strain originating from sheep scrapie) - cannot be easily extrapolated to relevant human prion strains, further questioning the utility of bioassays.

Characterization of the 263K-derived microsomal fraction: a source of prions for nanofiltration validation studies.

Background: The manufacturing processes of plasma products include steps that can remove prions. The efficacy of these steps is measured in validation studies using animal brain-derived prion materials called spikes. Because the nature of the prion agent in blood is not known, the relevance of these spikes, particularly with steps that are based on retention mechanisms such as nanofiltration, is important to investigate.

The Smallest Infectious Substructure Encoding the Prion Strain Structural Determinant Revealed by Spontaneous Dissociation of Misfolded Prion Protein Assemblies.

It is commonly accepted that the prion replicative propensity and strain structural determinant (SSD) are encoded in the fold of PrP amyloid fibril assemblies. By exploring the quaternary structure dynamicity of several prion strains, we revealed that all mammalian prion assemblies exhibit the generic property of spontaneously generating two sets of discreet infectious tetrameric and dimeric species differing significantly by their specific infectivity. By using perturbation approaches such as dilution and ionic strength variation, we demonstrated that these two oligomeric species were highly dynamic and evolved differently in the presence of chaotropic agents.