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.
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.
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.
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.
Given the increasingly widespread occurrence of bovine spongiform encephalopathy in Europe and Asia, there is a major need for widespread CJD surveillance.
The relationships between the degree of cortical prion protein (PrP) deposition, tissue vacuolation and astrocytosis were studied in the frontal cortex of 27 cases of human spongiform encephalopathy, encompassing 13 cases of sporadic Creutzfeldt-Jakob disease (sCJD), four cases of familial CJD (fCJD) (one owing to E200K mutation, one owing to 144 bp insertion, one owing to P102L mutation and one owing to A117V mutation), five cases of iatrogenic CJD (iCJD) owing to growth hormone therapy and five cases of variant CJD (vCJD).
A heterozygous T183A mutation in the prion protein (PrP) gene, PRNP, was identified in a patient with histopathologically confirmed spongiform encephalopathy.
Such conformations occurred spontaneously in Tg2866 mice expressing high levels of MoPrP(C)(P101L) as well as in Tg196 mice expressing low levels of MoPrP(C)(P101L) that were inoculated with brain extracts from ill Tg2866 mice, with a synthetic peptide with the P101L mutation and folded into a beta-rich structure, or with prions recovered from sheep with scrapie or cattle with bovine spongiform encephalopathy.
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.
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).
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.
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.
Chronic wasting disease and atypical forms of bovine spongiform encephalopathy and scrapie are not transmissible to mice expressing wild-type levels of human prion protein.
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).
Unexpectedly, bovine spongiform encephalopathy and variant CJD prions caused rapid neurological dysfunction in Tg(M109) mice upon second passage, with incubation periods of 64 and 40 days, respectively.
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.
We demonstrate that transgenic mice expressing both variant and wild-type human PrP are completely resistant to both kuru and classical Creutzfeldt-Jakob disease (CJD) prions (which are closely similar) but can be infected with variant CJD prions, a human prion strain resulting from exposure to bovine spongiform encephalopathy prions to which the Fore were not exposed.
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.