A prion in the Scrapie
form (PrPSc) is an infectious agent composed of protein in a misfolded
form. This is the central idea of the
Prion Hypothesis, which remains debated. This would be in contrast to all other
known infectious agents, like viruses, bacteriam fungi or parasites—which must
contain nucleic acids (eitherDNA, RNA, or both). The word prion, coined
in 1982 by Stanley B. Prusiner, is derived from the words protein and infection.
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 Creutzbeldt-Jakob
Disease (CJD), variant Creutzfeldt-Jakob Disease (vCJD), Gerstmann-Straussler-Sheinker
syndrome, Fatal Familial Insomnia and kuru. All known prion diseases in mammals affect the
structure of the brain or other neural tissue and all are currently untreatable
and universally fatal. In 2013, a study revealed that 1 in 2,000
people in the United Kingdom
Prions are not considered living organisms but may 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. 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 exponental growth rate associated with prion replication, which is a balance between the linear growth and the breakage of aggregates. (Note that 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.)
This altered structure is extremely stable and accumulates in infected tissue, causing tissue damage and cell death. 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.
All known mammalian prion diseases are caused by the so-called prion protein, PrP. The endogenous, properly folded form is denoted PrPC (for Common or Cellular), whereas the disease-linked, misfolded form is denoted PrPSc (for Scrapie, after one of the diseases first linked to prions and neurodegeneration.) The precise structure of the prion is not known, though they can be formed by combining PrPC, polyadenylic acid, and lipids in a Protein-Misfolding Cyclic Amplification (PMCA) reaction.
Proteins showing prion-type behavior are also found in some fungi, which has been useful in helping to understand mammalian prions. Fungal prions do not appear to cause disease in their hosts.
Prions are not considered living organisms but may 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. 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 exponental growth rate associated with prion replication, which is a balance between the linear growth and the breakage of aggregates. (Note that 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.)
This altered structure is extremely stable and accumulates in infected tissue, causing tissue damage and cell death. 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.
All known mammalian prion diseases are caused by the so-called prion protein, PrP. The endogenous, properly folded form is denoted PrPC (for Common or Cellular), whereas the disease-linked, misfolded form is denoted PrPSc (for Scrapie, after one of the diseases first linked to prions and neurodegeneration.) The precise structure of the prion is not known, though they can be formed by combining PrPC, polyadenylic acid, and lipids in a Protein-Misfolding Cyclic Amplification (PMCA) reaction.
Proteins showing prion-type behavior are also found in some fungi, which has been useful in helping to understand mammalian prions. Fungal prions do not appear to cause disease in their hosts.
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