Prions are infectious agents composed solely of misfolded proteins. Unlike viruses or bacteria, they contain no nucleic acid; instead, they are aberrant conformations of the host‑encoded prion protein that can induce the same misfolded state in normal molecules.
Biochemical nature and pathogenesis
The normal cellular prion protein (PrPC) is a glycosylphosphatidylinositol‑anchored protein expressed on the surface of neurons and other cells. Prions arise when this protein adopts a β‑sheet‑rich conformation (PrPSc) that is resistant to proteases, heat and disinfectants. The misfolded isoform acts as a template, binding to PrPC and promoting its conversion into more PrPSc. Aggregation of these misfolded proteins leads to the formation of amyloid fibrils and insoluble plaques in nervous tissue. Because prions lack nucleic acids, they do not encode enzymes or replicate by synthesis; propagation is purely conformational. Transmission occurs by ingestion of contaminated tissue, iatrogenic exposure or inherited mutations that favour misfolding. Prion diseases have long incubation periods, followed by rapid neurodegeneration characterised by vacuolation of gray matter (spongiform change), astrocytosis and absence of inflammatory response.
Diseases and epidemiological importance
Prion diseases, collectively known as transmissible spongiform encephalopathies, affect humans and animals. In humans, these include sporadic Creutzfeldt‑Jakob disease (CJD), familial CJD, kuru, fatal familial insomnia and Gerstmann–Sträussler–Scheinker syndrome. Variant CJD emerged after exposure to bovine spongiform encephalopathy (BSE)–infected beef in the 1990s, demonstrating cross‑species transmission. Animal prion diseases include scrapie in sheep, chronic wasting disease in deer and elk, and BSE in cattle. They are invariably fatal and currently lack effective treatment. Strict controls on animal feed, surveillance of livestock and sterilization procedures for surgical instruments are critical to prevent transmission. Diagnosis relies on clinical features, electroencephalography, cerebrospinal fluid biomarkers and detection of PrPSc by protein misfolding cyclic amplification or real‑time quaking‑induced conversion assays.
The discovery of prions revolutionised our understanding of infectious agents by showing that proteins alone can transmit disease. Their unique biology raises challenges for food safety, medicine and neurodegenerative disease research.
Related Terms: PrPSc, PrPC, Transmissible spongiform encephalopathy, Protein misfolding, Bovine Spongiform Encephalopathy