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A prion ( ) is a misfolded protein that induces folding problems in normal variants of the same protein, leading to cellular death.

Prions are responsible for prion diseases, which are fatal and transmissible neurodegenerative diseases affecting animals, including humans. These proteins can misfold sporadically, due to genetic mutations, or through exposure to an already misfolded protein, leading to an abnormal three-dimensional structure that can propagate misfolding in other proteins. The term prion derives from "proteinaceous infectious particle". Prions are primarily twisted isoforms of the major prion protein (PrP), a naturally occurring protein with an uncertain function. They are the hypothesized cause of various diseases, including scrapie in sheep, chronic wasting disease (CWD) in deer, bovine spongiform encephalopathy (BSE) in cattle (mad cow disease), and Creutzfeldt–Jakob disease (CJD) in humans. All known prion diseases in mammals affect the structure of the brain or other neural tissues. Most prion diseases were thought to be caused by PrP until 2015 when a prion form of alpha-synuclein was linked to multiple system atrophy (MSA). Misfolded proteins are also linked to other neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS), which have been shown to originate and progress by a prion-like mechanism. Prions are a type of intrinsically disordered protein that continuously changes conformation unless bound to a specific partner, such as another protein. Once a prion binds to another in the same conformation, it stabilizes and can form a fibril, leading to abnormal protein aggregates called amyloids.

The normal form of the protein is called PrPC, while the infectious form is called PrPSc – the C refers to 'cellular' PrP, while the Sc refers to 'scrapie', the prototypic prion disease, occurring in sheep.

Many different mammalian species can be affected by prion diseases, as the prion protein (PrP) is very similar in all mammals. The human prion disease variant Creutzfeldt–Jakob disease, however, is thought to be caused by a prion that typically infects cattle (causing bovine spongiform encephalopathy) and that is transmitted through infected meat. Until 2015 all known mammalian prion diseases were considered to be caused by the prion protein, PrP.

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. Research into fungal prions has given strong support to the protein-only concept, since purified protein extracted from cells with a prion state has been demonstrated to convert the normal form of the protein into a misfolded form in vitro, and in the process, preserve the information corresponding to different strains of the prion state. The characteristic prion domains may vary among species – e.g., characteristic fungal prion domains are not found in mammalian prions.

This has been shown by attaching the prion domain to a reporter protein, which then aggregates like a known prion. Similarly, removing the prion domain from a fungal prion protein inhibits prionogenesis. This modular view of prion behaviour has led to the hypothesis that similar prion domains are present in animal proteins, in addition to PrP.

His second hypothesis forms the basis of the modern prion theory, and proposed that an abnormal form of a cellular protein can convert normal proteins of the same type into its abnormal form, thus leading to replication. The protein was named a prion, for "proteinacious infectious particle", derived from the words protein and infection. Following the discovery of the same protein in different form in uninfected individuals, the specific protein that the prion was composed of was named the prion protein (PrP), and Griffith's second hypothesis, that an abnormal form of a host protein can convert other proteins of the same type into its abnormal form, became the dominant theory.

Quick Facts

• Most prion diseases were thought to be caused by PrP until 2015 when a prion form of alpha-synuclein was linked to multiple system atrophy (MSA).
• Once a prion binds to another in the same conformation, it stabilizes and can form a fibril, leading to abnormal protein aggregates called amyloids.
• Prions are responsible for prion diseases, which are fatal and transmissible neurodegenerative diseases affecting animals, including humans.
• All known prion diseases in mammals affect the structure of the brain or other neural tissues.
• Prions are primarily twisted isoforms of the major prion protein (PrP), a naturally occurring protein with an uncertain function.

Source material: Wikipedia - "Prion". Adapted and summarized for DiscoverScroll. Original contributors are credited through the linked Wikipedia article. Read original on Wikipedia. CC BY-SA 4.0. Changes were made from the original.