Abstract
A cellular prion protein (PrPC) is a ubiquitous cell surface glycoprotein, and its physiological functions have been receiving increased attention. Endogenous PrPC is present in various kidney tissues and undergoes glomerular filtration. In prion diseases, abnormal prion proteins are found to accumulate in renal tissues and filtered into urine. Urinary prion protein could serve as a diagnostic biomarker. PrPC plays a role in cellular signaling pathways, reno-protective effects, and kidney iron uptake. PrPC signaling affects mitochondrial function via the ERK pathway and is affected by the regulatory influence of microRNAs, small molecules, and signaling proteins. Targeting PrPC in acute and chronic kidney disease could help improve iron homeostasis, ameliorate damage from ischemia/reperfusion injury, and enhance the efficacy of mesenchymal stem/stromal cell or extracellular vesicle-based therapeutic strategies. PrPC may also be under the influence of BMP/Smad signaling and affect the progression of TGF-β-related renal fibrosis. PrPC conveys TNF-α resistance in some renal cancers, and therefore, the coadministration of anti-PrPC antibodies improves chemotherapy. PrPC can be used to design antibody–drug conjugates, aptamer–drug conjugates, and customized tissue inhibitors of metalloproteinases to suppress cancer. With preclinical studies demonstrating promising results, further research on PrPC in the kidney may lead to innovative PrPC-based therapeutic strategies for renal disease.
Highlights
Stembio, Ltd., Entrepreneur 306, Soonchunhyang-ro 22, Sinchang-myeon, Asan 31538, Korea; Department of Biochemistry, Soonchunhyang University College of Medicine, Cheonan 31151, Korea; Department of Biochemistry, BK21FOUR Project2, College of Medicine, Soonchunhyang, Medical Science Research Institute, Soonchunhyang University Seoul Hospital, Seoul 04401, Korea; Abstract: A cellular prion protein (PrPC ) is a ubiquitous cell surface glycoprotein, and its physiological functions have been receiving increased attention
PrPC functions in renal physiology and many pathologies where the kidney is either at the center of the disease etiology or suffers from secondary exposure to cellular toxins resulting from other organs, a rigorous characterization of PrPC in kidneys has been trailing behind, and several questions remain
PrPC expression at the transcript and protein levels in different animal models and serum or plasma samples from a human cohort all concluded that PrPC reports statistically significant differential expressions in kidney tissues for renal and prion diseases, yet the direction of changes in the PrPC expressions diverged, as the reported data alternated between overexpression and downregulation, depending on the model and experimental conditions
Summary
A cellular prion protein (PrPC ) is a glycoprotein on the cell surface. This particular protein has drawn extensive attention and investigation since it was first proposed that infective misfolded PrPC could be responsible for various neurodegenerative disorders that are often referred to as transmissible spongiform encephalopathies (TSEs) or, more commonly, prion disease [1,2]. It has been well-documented that PrPC exists in two distinct conformations: first, the host-encoded cellular prion protein that carries out the normal physiological functions (PrPC ), and second, the misfolded infective isoform that is often called pathogenic prion protein (usually denoted as PrPSc ) [7]. Scrapie-affected sheep have pathological prion proteins (PrPSc ) deposited at the intraepithelial and interstitial tissues of the kidney [26]. In sCJD patients, prion seeding activities occurs in the kidney as a result of infective prions flowing out from the central nervous system and infecting kidneys and adrenal glands to produce pathological prion proteins onsite [31] The detection of these disease-related prion proteins via urine screening is suggested as a novel method for diagnosing sCJD [32]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
