A prion (Listeni/ˈprɒn/[1]) is an infectious agent thought to be the cause of the transmissible spongiform encephalopathies (TSEs). It is composed entirely of protein material, called PrP (short for prion protein), that can fold in multiple, structurally distinct ways, at least one of which is transmissible to other prion proteins, leading to disease that is similar to viral infection. The word prion, coined in 1982 by Stanley B. Prusiner, is a compound word derived from protein and infection, hence prion, and is short for “proteinaceous infectious particle”,[2] in reference to its ability to self-propagate and transmit its conformation to other proteins.[3] Prions were initially identified as the causative agent in animal TSEs such as bovine spongiform encephalopathy (BSE)—known popularly as “mad cow disease”—and scrapie in sheep. Human prion diseases include Creutzfeldt-Jakob Disease (CJD) and its variant (vCJD), Gerstmann–Sträussler–Scheinker syndrome, Fatal Familial Insomnia, and kuru.[4] A 2015 study concluded that multiple system atrophy (MSA), a rare human neurodegenerative disease, is caused by a misfolded version of a protein called alpha-synuclein, and is therefore also classifiable as a prion disease.[5] Several yeast proteins have been identified as having prionogenic properties as well.[6][7]

A protein as a standalone infectious agent stands in contrast to all other known infectious agents such as viruses, bacteria, fungi, and parasites, all of which contain nucleic acids (DNA, RNA, or both). For this reason, a minority of researchers still consider the prion/TSE hypothesis unproven.[8] All known prion diseases in mammals affect the structure of the brain or other neural tissue; all are currently untreatable and universally fatal.[9]

Prions may propagate by transmitting their misfolded protein state: When a prion enters a healthy organism, it induces existing, properly folded proteins to convert into the misfolded prion form. In this way, the prion acts as a template to guide the misfolding of more proteins into prion form. In yeast, this refolding is assisted by chaperone proteins such as Hsp104p. These refolded prions can then go on to convert more proteins themselves, leading to a chain reaction resulting in large amounts of the prion form.[7] All known prions induce the formation of an amyloid fold, in which the protein polymerises into an aggregate consisting of tightly packed beta sheets. Amyloid aggregates are fibrils, growing at their ends, and replicate when breakage causes two growing ends to become four growing ends. The incubation period of prion diseases is determined by the exponential growth rate associated with prion replication, which is a balance between the linear growth and the breakage of aggregates.[10] The propagation of the prion depends on the presence of normally folded protein in which the prion can induce misfolding; animals that do not express the normal form of the prion protein can neither develop nor transmit the disease.

Prion aggregates are extremely stable and accumulate in infected tissue, causing tissue damage and cell death.[11] This structural stability means that prions are resistant todenaturation by chemical and physical agents, making disposal and containment of these particles difficult. Prion structure varies slightly between species, but nonetheless prion replication is subject to occasional epimutation and natural selection just like other forms of replication.[12]