Prion diseases are transmissible experimentally and naturally, selleck compound and enormous

efforts have been directed towards establishing the nature of the transmissible agent. Stanley Prusiner proposed the prion hypothesis in 1982, suggesting that the transmissible agent was composed entirely of a modified host protein, the prion protein (PrP), which was partially resistant to proteolytic degradation, with no nucleic acid component [3]. The normal form of the prion protein (PrPc) is expressed at the highest levels in neurones within the brain [2]. In prion diseases, an abnormal isoform of PrP (designated PrPSc) accumulates in the brain, with an identical amino acid sequence to PrPc, but an increased beta-sheet content that renders it relatively resistant to proteolytic digestion [2]. PrPSc is (at least) the main constituent of the transmissible agent and is closely associated with infectivity. The high beta sheet

content of PrPSc confers stability; conventional means of bacterial and viral decontamination are generally ineffective for prions. None of the current measures recommended for decontamination of prions is guaranteed to remove all infectivity [4], and these measures are not applicable to learn more blood or plasma products. The commonest human prion disease is sporadic Creutzfeldt–Jakob disease (CJD), which has an incidence of around 1.5 per million of the population, with a worldwide distribution [5]. The causes of sporadic CJD are unknown, but there is evidence of a genetic predisposition. In the human prion protein gene (PRNP) located on chromosome 20, there is a naturally occurring polymorphism at codon 129, which can encode either methionine or valine (Table 2) [6]. In contrast to the normal Caucasian population, there is a predominance of homozygotes in sporadic CJD, particularly methionine homozygotes (Table 2). Surveillance of CJD was

recommenced in the Pazopanib chemical structure United Kingdom (UK) in 1990, to identify any possible effects of BSE. Over 180 000 clinical cases of BSE have been identified in the UK since the 1980s, but when allowances are made for asymptomatic infections, it has been estimated that up 3 million infected cattle may have entered the UK human food chain [7]. In 1996, the National CJD Surveillance Unit reported a new form of human prion disease in the UK, now known as variant CJD [8]. Variant CJD has a clinical and pathological phenotype that is distinct from sporadic CJD [9]. All probable and definite variant CJD patients who have undergone genetic testing are methionine homozygotes at the codon 129 polymorphism of the PRNP gene, indicating susceptibility to variant CJD in this genetic subset. However, a recent possible case of variant CJD has been reported in a heterozygote (methionine/valine) at this genetic locus [10].