Harnessing the Physiological Functions of Cellular Prion Protein in the Kidneys: Applications for Treating Renal Diseases

A cellular prion protein (PrP(C)) is a ubiquitous cell surface glycoprotein, and its physiological functions have been receiving increased attention. Endogenous PrP(C) 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. PrP(C) plays a role in cellular signaling pathways, reno-protective effects, and kidney iron uptake. PrP(C) signaling affects mitochondrial function via the ERK pathway and is affected by the regulatory influence of microRNAs, small molecules, and signaling proteins. Targeting PrP(C) 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. PrP(C) may also be under the influence of BMP/Smad signaling and affect the progression of TGF-β-related renal fibrosis. PrP(C) conveys TNF-α resistance in some renal cancers, and therefore, the coadministration of anti-PrP(C) antibodies improves chemotherapy. PrP(C) 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 PrP(C) in the kidney may lead to innovative PrP(C)-based therapeutic strategies for renal disease.