Transmissible spongiform encephalopathies (TSEs) are a group of devastating neurodegenerative diseases characterized by the conversion of the normal cellular prion protein (PrPC) into its misfolded, pathogenic form, PrPSc. Despite significant research, the exact molecular mechanisms driving PrPC to PrPSc conversion remain elusive and are thought to involve multiple molecules or cofactors. One protein of interest, SERPINA3 (murine SerpinA3n), is an acute-phase protein, a member of the serine protease inhibitor family. Intriguingly, SERPINA3 expression is notably upregulated in the brains of patients with Creutzfeldt-Jakob disease and in mice experimentally infected with prions, suggesting a potential role in prion disease pathology. In this study, we deepened the role of SerpinA3n in prion conversion and propagation by utilizing SerpinA3n-deficient (SerpinA3n−/−) mice intracerebrally injected with the RML, 139A, or ME7 prion strains. Our results showed that the specific absence of SerpinA3n did not significantly affect prion propagation, as evidenced by the lack of notable changes in clinical and neuropathological assessments. Compensatory mechanisms involving other serpins or molecules may mitigate the effects of the specific absence of SerpinA3n, thereby maintaining efficient prion propagation.
