Transmissible Spongiform Encephalopathy In Sheep Research Articles

Screening Congo Red and its analogues for their ability to prevent the formation of PrP-res in scrapie-infected cells.

Transmissible spongiform encephalopathies (TSEs) are incurable, fatal diseases. The dye Congo Red (CR) can cure cells infected with agents of the sheep TSE, scrapie, but is not used as a therapeutic or prophylactic agent in vivo, as its effects are small, possibly due to low blood-brain barrier permeability, and complicated by its intrinsic carcinogenicity. In this paper, the development is described of a structure-activity profile for CR by testing a series of analogues of this dye for their ability to inhibit the formation of the protease-resistant prion protein, PrP-res, a molecular marker for the infectious agent, in the scrapie-infected, SMB cell line. It was found that the central benzidine unit in CR, which gives the molecule potential carcinogenicity, can be replaced by other, less toxic moieties and that the sulphonate groups on the core molecule can be replaced by carboxylic acids, which should improve the brain permeability of these compounds. However, detailed dose-response curves were generated for several derivatives and they revealed that, while some compounds showed inhibition of PrP-res accumulation at high concentrations, at low concentrations they actually stimulated levels of PrP-res above control values.

Epidemic of transmissible spongiform encephalopathy in sheep and goats in Italy

Epidemic of transmissible spongiform encephalopathy in sheep and goats in Italy

Bovine spongiform encephalopathy (BSE): causes and consequences of a common source epidemic.

Bovine spongiform encephalopathy (BSE) is a transmissible spongiform encephalopathy (TSE) or prion disease of cattle first recognized in 1986 in the United Kingdom, where it produced a common source epidemic that peaked in January 1993 and has subsided markedly since that time. The epidemic began simultaneously at many geographic locations and was traced to contamination of meat and bone meal (MBM), a dietary supplement prepared from rendering of slaughterhouse offal. It appears that the epidemic was initiated by the presence of the agent of scrapie (a long-standing TSE of sheep) that was first transmitted to cattle, beginning in the early 1980s, when most rendering plants abandoned the use of organic solvents in the preparation of MBM. The epidemic was probably accelerated by the recycling of infected bovine tissues prior to the recognition of BSE. To terminate the epidemic, a prohibition on the feeding of ruminant-derived protein to ruminants was introduced in the United Kingdom in July 1988. The ruminant feed ban accounts for the decline of the epidemic after an interval of about 5 years, approximately equivalent to the average incubation period of BSE. Relatively few cases of BSE have occurred in cattle born after 1993, and it is predicted that the epidemic will terminate about the year 2000 based on an extrapolation of the present declining curve. A comparison of data from the United Kingdom with data from relatively low incidence countries, such as Switzerland, indicates that this epidemic has been mainly confined to the United Kingdom because of a unique concatenation of risk factors, including: 1) a high ratio of sheep to cattle; 2) a relatively high rate of endemic scrapie; 3) the heavy feeding of MBM to dairy cattle; and 4) changes in the rendering process used to prepare MBM. Recently, cases of a variant form of Creutzfeldt-Jakob disease (a TSE of humans) have been reported in the United Kingdom. These cases, at least 10 of which had onset in 1994-1995, are distinguished by their occurrence in subjects under age 40 years, by their clinical presentation, and by their neurohistopathologic picture. The appearance of this novel disease and its concentration in the United Kingdom have raised the question that it might represent the transmission of BSE to humans. However, the cases gave no history indicating an unusual exposure to live cattle, to the preparation of beef products, or of dietary exposure to bovine tissues, and it remains to be determined whether they are associated with BSE.

A 60-kDa Prion Protein (PrP) with Properties of Both the Normal and Scrapie-associated Forms of PrP

Scrapie is a transmissible spongiform encephalopathy of sheep and other mammals in which disease appears to be caused by the accumulation of an abnormal form of a host protein, prion protein (PrP), in the brain and other tissues. The process by which the normal protease-sensitive form of PrP is converted into the abnormal protease-resistant form is unknown. Several hypotheses predict that oligomeric forms of either the normal or abnormal PrP may act as intermediates in the conversion process. We have now identified a 60-kDa PrP derived from hamster PrP expressed in murine neuroblastoma cells. Peptide mapping studies provided evidence that the 60-kDa PrP was composed solely of PrP and, based on its molecular mass, appeared to be a PrP dimer. The 60-kDa PrP was not dissociated under several harsh denaturing conditions, which indicated that it was covalently linked. It was similar to the disease-associated form of PrP in that it formed large aggregates. However, it resembled the normal form of PrP in that it was sensitive to proteinase K and had a short metabolic half-life. The 60-kDa PrP, therefore, had characteristics of both the normal and disease-associated forms of PrP. Formation and aggregation of the 60-kDa hamster PrP occurs in uninfected mouse neuroblastoma cells, which suggests that hamster PrP has a predisposition to aggregate even in the absence of scrapie infectivity. Similar 60-kDa PrP bands were identified in scrapie-infected hamster brain but not in uninfected brain. Therefore, a 60-kDa molecule might participate in the scrapie-associated conversion of protease-sensitive PrP to protease-resistant PrP.