Prion

Prion refers to a misfolded protein that acts as an infectious agent and causes transmissible spongiform encephalopathies in humans and animals. The disease-associated form, PrPSc, arises from the normal cellular prion protein, PrPC, through a conformational change. PrPC is encoded by the PRNP gene and is typically rich in alpha helices; PrPSc is beta-sheet–rich and tends to aggregate, forming amyloid deposits that resist proteolysis.

Prions propagate by templated misfolding: existing PrPSc converts PrPC into more PrPSc, enabling self-sustaining spread without nucleic acids. They are not considered living organisms and lack detectable nucleic acid.

Transmission occurs as sporadic disease in most cases, through inherited PRNP mutations in a minority, or via acquired exposure to contaminated tissue, medical procedures, or, in rare instances, cross-species transmission with variable efficiency (the species barrier). Pathology includes spongiform degeneration of the brain with vacuolation, neuronal loss, and gliosis.

Prion diseases in humans include sporadic Creutzfeldt-Jakob disease, familial CJD, variant CJD linked to bovine spongiform encephalopathy, as well as genetic disorders such as Gerstmann-Sträussler-Scheinker syndrome and fatal familial insomnia. In animals, scrapie in sheep and goats, bovine spongiform encephalopathy in cattle, and chronic wasting disease in cervids are recognized.

Diagnosis often relies on neurologic assessment and supports with postmortem neuropathology. Antemortem tests such as real-time quaking-induced conversion (RT-QuIC) on cerebrospinal fluid or nasal brushings, MR imaging findings, and elevated CSF 14-3-3 protein can aid diagnosis. Definitive confirmation usually requires examination of brain tissue.

There is no cure; treatment is supportive. Prions are unusually resistant to standard sterilization, necessitating strict infection-control measures. The concept of prions was proposed by Stanley B. Prusiner in 1982, leading to the Nobel Prize in Physiology or Medicine in 1997.