Major prion protein (aggregated oligomeric forms) (PrPSc)

The major prion protein (PrP) is a cell-surface glycoprotein primarily expressed in the central nervous system (UniProt: P04156). While its cellular form (PrPC) is involved in neuroprotection and synaptic function, it can undergo a conformational change into a misfolded, aggregated, and infectious isoform known as PrPSc (PubMed: 29443161). These aggregated oligomeric forms serve as templates that induce further misfolding of PrPC, leading to the accumulation of toxic protein aggregates and the development of transmissible spongiform encephalopathies (TSEs) (NIH: Prion Diseases). Prion diseases, such as Creutzfeldt-Jakob disease, are characterized by rapid neurodegeneration and are invariably fatal. Therapeutic efforts target these oligomeric forms by inhibiting the conversion process, promoting the clearance of existing aggregates, or reducing the substrate PrPC levels (PubMed: 31430140). Despite numerous experimental approaches, including small molecules like Anle138b and monoclonal antibodies like PRN100, effective clinical treatments remain a significant challenge (PubMed: 35110345).

Other names

PrPScPrP-resScrapie prion proteinCD230PrP27-30Prion protein (p27-30)

Therapeutic strategies focus on reducing the expression of the cellular prion protein (PrPC), stabilizing the PrPC conformation to prevent misfolding, or directly targeting and clearing the aggregated oligomeric PrPSc forms to halt neurotoxic signaling and propagation (PubMed: 31430140).