β-Cleavage of the prion protein in the human eye: Implications for the spread of infectious prions and human ocular disorders.

Autor: Chaudhary S; Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH, 44106, USA., Ashok A; Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH, 44106, USA., Wise AS; Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH, 44106, USA., Rana NA; Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH, 44106, USA., Kritikos AE; Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH, 44106, USA., Lindner E; Department of Ophthalmology, Medical University of Graz, Auenbruggerplatz 4, 8036, Graz, Austria., Singh N; Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH, 44106, USA. Electronic address: neena.singh@case.edu.
Jazyk: angličtina
Zdroj: Experimental eye research [Exp Eye Res] 2021 Nov; Vol. 212, pp. 108787. Date of Electronic Publication: 2021 Oct 07.
DOI: 10.1016/j.exer.2021.108787
Abstrakt: Recently, we reported β-cleavage of the prion protein (PrP C ) in human ocular tissues. Here, we explored whether this is unique to the human eye, and its functional implications. A comparison of the cleavage pattern of PrP C in human ocular tissues with common nocturnal and diurnal animals revealed mainly β-cleavage in humans, and mostly full-length PrP C in animal retinas. Soluble FL PrP C and N-terminal fragment (N2) released from β-cleavage was observed in the aqueous and vitreous humor (AH & VH). Expression of human PrP C in ARPE-19 cells, a human retinal pigmented epithelial cell line, also showed β-cleaved PrP C . Surprisingly, β-cleavage was not altered by a variety of insults, including oxidative stress, suggesting a unique role of this cleavage in the human eye. It is likely that β-cleaved C- or N-terminal fragments of PrP C protect from various insults unique to the human eye. On the contrary, β-cleaved C-terminus of PrP C is susceptible to conversion to the pathological PrP-scrapie form, and includes the binding sites for β1-integrin and amyloid-β, molecules implicated in several ocular disorders. Considering the species and tissue-specific cleavage of PrP C , our data suggest re-evaluation of prion infectivity and other ocular disorders of the human eye conducted in mouse models.
(Copyright © 2021 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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