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A prion (i/ˈpriːɒn/[1]) in the Scrapie form (PrPSc) is an infectious agent composed of protein in a misfolded form.[2] This is the central idea of the Prion Hypothesis, which remains debated.[3] This would be in contrast to all other known infectious agents (virus/bacteria/fungus/parasite) which must contain nucleic acids (either DNA, RNA, or both). The word prion, coined in 1982 by Stanley B. Prusiner, is derived from the words protein and infection.[4] Prions are responsible for the transmissible spongiform encephalopathies in a variety of mammals, including bovine spongiform encephalopathy (BSE, also known as "mad cow disease") in cattle. In humans, prions cause Creutzfeldt-Jakob Disease (CJD), variant Creutzfeldt-Jakob Disease (vCJD), Gerstmann–Sträussler–Scheinker syndrome, Fatal Familial Insomnia and kuru.[5] All known prion diseases affect the structure of the brain or other neural tissue and all are currently untreatable and universally fatal.[6]

Prions, like viruses, are not actually alive, although both can reproduce by hijacking the functions of living cells.[7]

Prions propagate by transmitting a misfolded protein state. If a prion enters a healthy organism, it induces existing, properly folded proteins to convert into the disease-associated, prion form; the prion acts as a template to guide the misfolding of more proteins into prion form. These newly formed prions can then go on to convert more proteins themselves; this triggers a chain reaction that produces large amounts of the prion form.[8] 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 replicating 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.[9] (Note that the propagation of the prion depends on the presence of normally folded protein in which the prion can induce misfolding; animals which do not express the normal form of the prion protein cannot develop nor transmit the disease.)

This altered structure is extremely stable and accumulates in infected tissue, causing tissue damage and cell death.[10] This structural stability means that prions are resistant to denaturation by chemical and physical agents, making disposal and containment of these particles difficult. Prions come in different strains, each with a slightly different structure, and most of the time, strains breed true. Prion replication is nevertheless subject to occasional epimutation and then natural selection just like other forms of replication.[11]

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