Prion protein facilitates retinal iron uptake and is cleaved at the β-site: Implications for retinal iron homeostasis in prion disorders.

ABSTRACT: Prion disease-associated retinal degeneration is attributed to PrP-scrapie (PrP^Sc), a misfolded isoform of prion protein (PrP^C) that accumulates in the neuroretina. However, a lack of temporal and spatial correlation between PrP^Sc and cytotoxicity suggests the contribution of host factors. We report retinal iron dyshomeostasis as one such factor. PrP^C is expressed on the basolateral membrane of retinal-pigment-epithelial (RPE) cells, where it mediates uptake of iron by the neuroretina. Accordingly, the neuroretina of PrP-knock-out mice is iron-deficient. In RPE19 cells, silencing of PrP^C decreases ferritin while over-expression upregulates ferritin and divalent-metal-transporter-1 (DMT-1), indicating PrP^C-mediated iron uptak

SUBMITTER: Asthana A 

PROVIDER: S-EPMC5575325 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature