Major prion protein (PRNP) (PrP^C)

The Major prion protein (PRNP), commonly referred to as the cellular prion protein (PrP^C), is a glycosylphosphatidylinositol (GPI)-anchored glycoprotein primarily expressed on the surface of neurons and glial cells in the central nervous system (UniProt P04156). While its precise physiological role remains a subject of ongoing research, PrP^C is known to participate in copper homeostasis, signal transduction, synaptic plasticity, and neuroprotection against oxidative stress (PubMed: 23115163). The protein is most notorious for its involvement in transmissible spongiform encephalopathies (TSEs), such as Creutzfeldt-Jakob disease, where the normal alpha-helical PrP^C undergoes a conformational change into a beta-sheet-rich, pathogenic isoform called PrP^Sc (NIH: Prion Diseases). Beyond prion diseases, PrP^C has been identified as a high-affinity receptor for amyloid-beta oligomers, suggesting a role in the neurotoxic signaling pathways of Alzheimer's disease (PubMed: 19242475). Therapeutic strategies currently focus on reducing PrP^C expression using antisense oligonucleotides or stabilizing the native structure with small molecules and antibodies to prevent misfolding and neurodegeneration (ClinicalTrials.gov: NCT06119074). Notable drug candidates include IONIS-PRNPRx, which targets the PRNP mRNA to lower protein levels, and PRN100, a monoclonal antibody designed to stabilize the cellular form (PubMed: 35444346).

Other names

PRNPCD230PrPPrion proteinASCRSialoglycoprotein PrP27-30

Antisense oligonucleotide-mediated reduction of PRNP mRNA levels to decrease protein expression; monoclonal antibody-mediated stabilization of the cellular prion protein structure or blockade of toxic oligomer binding.