Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Chaudhary, S; Ashok, A; Wise, AS; Rana, NA; Kritikos, AE; Lindner, E; Singh, N.
β-Cleavage of the prion protein in the human eye: Implications for the spread of infectious prions and human ocular disorders.
EXP EYE RES. 2021; 212: 108787
Doi: 10.1016/j.exer.2021.108787
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- Lindner Ewald
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- Abstract:
- Recently, we reported β-cleavage of the prion protein (PrPC) 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 PrPC in human ocular tissues with common nocturnal and diurnal animals revealed mainly β-cleavage in humans, and mostly full-length PrPC in animal retinas. Soluble FL PrPC and N-terminal fragment (N2) released from β-cleavage was observed in the aqueous and vitreous humor (AH & VH). Expression of human PrPC in ARPE-19 cells, a human retinal pigmented epithelial cell line, also showed β-cleaved PrPC. 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 PrPC protect from various insults unique to the human eye. On the contrary, β-cleaved C-terminus of PrPC 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 PrPC, our data suggest re-evaluation of prion infectivity and other ocular disorders of the human eye conducted in mouse models.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals - administration & dosage
- Cell Line - administration & dosage
- Disease Models, Animal - administration & dosage
- Eye Diseases - metabolism
- Humans - administration & dosage
- Mice - administration & dosage
- PrPC Proteins - metabolism
- RNA Cleavage - physiology
- Retinal Pigment Epithelium - metabolism, pathology
- Find related publications in this database (Keywords)
- Prion protein
- I3-Cleavage
- Retina
- Aqueous humor
- Vitreous humor