Prion information

Prion
3D structure of major prion protein
Pronunciation	/ˈpriːɒn/ ⓘ, /ˈpraɪɒn/[1][2]
Specialty	Infectious diseases

A prion /ˈpriːɒn/ ^ⓘ is a misfolded protein that can induce misfolding of normal variants of the same protein and trigger cellular death. Prions cause prion diseases known as transmissible spongiform encephalopathies (TSEs) that are transmissible, fatal neurodegenerative diseases in humans and animals.^[3][4] The proteins may misfold sporadically, due to genetic mutations, or by exposure to an already misfolded protein.^[5] The consequent abnormal three-dimensional structure confers on them the ability to cause misfolding of other proteins.

The word prion is derived from the term "proteinaceous infectious particle".^[6][7] The hypothesized role of a protein as an infectious agent stands in contrast to all other known infectious agents such as viroids, viruses, bacteria, fungi, and parasites, all of which contain nucleic acids (DNA, RNA, or both).

Most prions are twisted isoforms of the major prion protein (PrP), a natural protein whose normal function is uncertain. They are hypothesized as the cause of transmissible spongiform encephalopathies (TSEs),^[8] including scrapie in sheep, chronic wasting disease (CWD) in deer, bovine spongiform encephalopathy (BSE) in cattle (mad cow disease), feline spongiform encephalopathy (FSE) in felines, and Creutzfeldt–Jakob disease (CJD) and fatal insomnia in humans.

All known prion diseases in mammals affect the structure of the brain or other neural tissue; all are progressive, have no known effective treatment, and are always fatal.^[9] All mammalian prion diseases were believed to be caused by PrP, until 2015, when a prion form of alpha-synuclein was hypothesized to cause multiple system atrophy (MSA).^[10]

Prions are a type of intrinsically disordered protein, which continuously change their conformation unless they are bound to a specific partner such as another protein. With a prion, two protein chains are stabilized if one binds to another in the same conformation. The probability of this happening is low, but once it does, the combination of the two is very stable. Then more units can get added, making a sort of "fibril".^[11] Prions form abnormal aggregates of proteins called amyloids, which accumulate in infected tissue and are associated with tissue damage and cell death.^[12] Amyloids are also associated with several other neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.^[13][14]

A prion disease is a type of proteopathy, or disease of structurally abnormal proteins. In humans, prions are believed to be the cause of Creutzfeldt–Jakob disease (CJD), its variant (vCJD), Gerstmann–Sträussler–Scheinker syndrome (GSS), fatal familial insomnia (FFI), and kuru.^[15] There is also evidence suggesting prions may play a part in the process of Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS); these have been termed prion-like diseases.^{[16][17][18][19]} Several yeast proteins have also been identified as having prionogenic properties,^[20][21] as well as a protein involved in modification of synapses during the formation of memories^[22][11] (see Eric Kandel § Molecular changes during learning). Prion replication is subject to epimutation and natural selection just as for other forms of replication, and their structure varies slightly between species.^[23]

Prion aggregates are stable, and this structural stability means that prions are resistant to denaturation by chemical and physical agents: they cannot be destroyed by ordinary disinfection or cooking. This makes disposal and containment of these particles difficult, and the risk of iatrogenic spread through medical instruments a growing concern.