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ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Virus and Prion Research » Research » Publications at this Location » Publication #396244

Research Project: Elucidating the Pathobiology and Transmission of Transmissible Spongiform Encephalopathies

Location: Virus and Prion Research

Title: Comparison of protein hallmarks of ferroptosis in mice with prion disease

item MATHIAS, CLAIRE - Iowa State University
item GREENLEE, HEATHER - Iowa State University
item Greenlee, Justin
item Cassmann, Eric

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 8/5/2022
Publication Date: 8/4/2022
Citation: Mathias, C.E., Greenlee, H.W., Greenlee, J.J., Cassmann, E.D. 2022. Comparison of protein hallmarks of ferroptosis in mice with prion disease (abstract). Meeting Abstract. p.198.

Interpretive Summary:

Technical Abstract: Transmissible spongiform encephalopathies are fatal neurodegenerative diseases associated with an accumulation of misfolded prion protein (PrPSc). Normally folded cellular prion proteins (PrPC) are expressed in mammalian cells and are involved in the maintenance of cellular iron homeostasis. It has been shown that prion disorders are associated with iron dyshomeostasis, leading to an imbalance in the brain’s metal metabolism. The underlying mechanism of iron dyshomeostasis in animals with prion disease—and its exact role in disease progression—is unclear. In other neurodegenerative diseases, such as Alzheimer’s and Parkinson’s disease, a new form of iron-related dyshomeostasis has been implicated in disease mechanism. Ferroptosis is a non-apoptotic form of regulated cell death. This specific form of iron dyshomeostasis relies on the accumulation of intracellular iron to trigger lipid peroxidation and rupture the cell membrane. Established protein hallmarks include acyl-CoA synthetase long-chain family member 4 (ACSL4), cyclooxygenase-2, and transferrin receptor. In this study, we hypothesized that the expression of these protein hallmarks would differ in the brain tissues of mice with prion disease and control mice. Western blots were analyzed comparing the abundance of targeted proteins in PrPSc-inoculated mice and non-inoculated mice. Initial results have shown a difference in the abundance of ACSL4 between these samples. Based on these findings, it is suggested that the expression of ferroptosis differs between mice with prion disease and mice without prion disease, and supports further investigation of the remaining protein hallmarks.