The structure of the infectious prion protein (PrPSc), which is responsible for Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy, has escaped all attempts at elucidation due to its insolubility and propensity to aggregate.
Prion protein (PrP) forms the fibrils or prion rods isolated from scrapie-infected brain and has been proposed as the major component of the infectious agent of this slowly progressive spongiform encephalopathy.
Amyloidogenic protein accumulation often occurs in the brain tissues, e.g. in Alzheimer's disease with the deposition of amyloid-beta and Tau, in scrapie and bovine spongiform encephalopathy with the accumulation of prion protein, in Parkinson's disease with the deposition of alpha-synuclein.
Given the increasingly widespread occurrence of bovine spongiform encephalopathy in Europe and Asia, there is a major need for widespread CJD surveillance.
Use of bovine recombinant prion protein and real-time quaking-induced conversion to detect cattle transmissible mink encephalopathy prions and discriminate classical and atypical L- and H-Type bovine spongiform encephalopathy.
A heterozygous T183A mutation in the prion protein (PrP) gene, PRNP, was identified in a patient with histopathologically confirmed spongiform encephalopathy.
Conformational change in the prion protein (PrP) is thought to be responsible for a group of rare but fatal neurodegenerative diseases of humans and other animals, including Creutzfeldt-Jakob disease and bovine spongiform encephalopathy.
Prion diseases such as bovine spongiform encephalopathy in cattle and Creutzfeldt-Jakob disease in humans are associated with the misfolding and accumulation of an abnormal conformation of the host-encoded prion protein (PrP).
In another patient, a single vacuolated neuron in the inferior olivary nuclei contained prominent intravacuolar granular PrP(res) deposits, resembling changes of brainstem neurons in bovine spongiform encephalopathy.
Knock-in transgenic mice (101LL) expressing mutant PrP (PrP-101L) that are susceptible to disease but do not develop any spontaneous neurological phenotype were inoculated with (i) brain extracts containing PrP(TSE) from healthy 101LL mice with PrP plaques in the corpus callosum or (ii) brain extracts from mice overexpressing PrP-101L with neurological disease, severe spongiform encephalopathy, and formation of proteinase K-resistant PrP(TSE).
In the absence of known CJD risk factors or prion protein gene abnormalities, the UK government concluded that the clustering of these cases may represent transmission to humans of the agent causing bovine spongiform encephalopathy.
The prion diseases, which include Creutzfeldt-Jakob disease in humans, chronic wasting disease in cervids (i.e., deer, elk, moose, and reindeer), bovine spongiform encephalopathy in cattle, as well as sheep and goat scrapie, are caused by the conversion of the cellular prion protein (PrP<sup>C</sup>) into a disease-causing conformer (PrP<sup>Sc</sup>).
The quantitative balance between PrP(Sc) types was maintained when variant Creutzfeldt-Jakob disease was transmitted to wild-type mice and was also found in bovine spongiform encephalopathy cattle brain, indicating that the agent rather than the host specifies their relative representation.
While loss of function of PrP does not elicit apparent phenotypes, generation of misfolded forms of the protein or its aberrant metabolic isoforms has been implicated in a number of neurodegenerative disorders such as scrapie, kuru, Creutzfeldt-Jakob disease, fatal familial insomnia, Gerstmann-Sträussler-Scheinker and bovine spongiform encephalopathy.
Cases of variant Creutzfeldt-Jakob disease in people who had consumed contaminated meat products from cattle with bovine spongiform encephalopathy emphasize the need for measures aimed at preventing the transmission of the pathogenic prion protein (PrPSc) from materials derived from cattle.
There were no mutations found in the Prp gene, so it is possible that there are SEs caused by genes or other pathological processes unrelated to the Prp gene.
This is capable of transforming the normal cellular prion protein (PrP<sup>C</sup>) into new infectious PrP<sup>Sc</sup> Interspecies prion transmissibility studies performed by experimental challenge and the outbreak of bovine spongiform encephalopathy that occurred in the late 1980s and 1990s showed that while some species (sheep, mice, and cats) are readily susceptible to TSEs, others are apparently resistant (rabbits, dogs, and horses) to the same agent.