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This lecture explores the dynamic nature of prion assemblies, focusing on the catalytic exchange between multiple conformations and the structural diversity observed during the replication process. The instructor discusses the physiological role of PrP protein, the triple determinisms of human prion diseases, the molecular basis of prion diseases, and the mechanisms of prion replication. The lecture also covers the Prion paradigm, conversion by templating, and the experimental constraints for model building. Additionally, it delves into the tissue spreading, neurotoxicity mechanisms, and the state of the art in 2022 regarding PrPSc structure and prion amplification. The exchange process between different subpopulations and the process of prion dissemination through the connectome are also highlighted.