Experimental study using multiple strains of prion disease in cattle reveals an inverse relationship between incubation time and misfolded prion accumulation, neuroinflammation and autophagy
Greenlee, M. Heather
Moore, S. Jo
Proteinopathies result from aberrant folding and accumulation of specific proteins. Currently, there is a lack of knowledge about the factors that influence disease progression making this a key challenge for the development of therapies for proteinopathies. Due to the similarities between transmissible spongiform encephalopathies (TSEs) and other protein misfolding diseases, TSEs can be used to understand other proteinopathies. Bovine spongiform encephalopathy (BSE) is a TSE that occurs in cattle and can be subdivided into three strains: classical BSE, and atypical BSEs (H-type and L-type) that have shorter incubation periods. The NLRP3 inflammasome is a critical component of the innate immune system that leads to release of IL-1β (Interlukin-1β). Macroautophagy is an intracellular mechanism that plays an essential role in protein clearance. In this study, we use the retina as a model to investigate the relationship between disease incubation period, prion protein (PrPSc) accumulation, neuroinflammation, and changes in macroautophagy. We demonstrate that atypical BSEs present with increased PrPSc accumulation and neuroinflammation, and decreased autophagy. Our work suggests a relationship between disease time course, neuroinflammation, and the autophagic stress response. This work may help identify novel therapeutic biomarkers that can delay or prevent the progression of proteinopathies.