A Theoretical Framework on the Biology of Prion Diseases.

Background: Prion diseases or TSE diseases are a group of neurodegenerative disorders that manifest in several forms in humans, such as Kuru disease, Creutzfeldt‒Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome (GSS) and fatal familial insomnia.

Objective: In this study, we propose a multimodular hypothesis of prion diseases. According to this hypothesis, a prion disease manifests because of the interaction of two genetic modules, such as the PRNP gene module and that of the gene or genes responsible for one or more chaperones, with one or some chemical module on whose structure the products of the genes or genetic modules interact.

Methods: This study presents the perspective that modular thinking can allow us to overcome conceptual obstacles in the understanding and interpretation of prion diseases.

Results and discussion: The structure of the chemical module or modules is directly responsible for the folding or misfolding of the PrP^C protein. The etiology of acquired prion diseases is explained based on this hypothesis. Hence, it has been proposed that (g) CJD involves the PRNP gene mutant and one or more mutant genes for one or more chaperone genes. In contrast, sCJD has one or more mutant chaperone genes. When does iCJD occur? Healthy individuals manifest acquired prion disease through contamination when infected with one or more mutant chaperones. The mutant chaperones interact with the prion protein, and PrP^C is converted to its isoform PrP^Sc. In a recent study, there was a case of an individual with CJD after COVID-19 infection.

Conclusion: This case emphasizes the link between neuroinflammation and protein misfolding and provides proof that chemical module formation is a necessary condition for the manifestation of prion diseases.