Academic literature on the topic 'Prion, copper, Transmissible spongiform encephalopathy'
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Journal articles on the topic "Prion, copper, Transmissible spongiform encephalopathy"
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Langeveld, J. P. M., J. G. Jacobs, N. Hunter, L. J. M. van Keulen, F. Lantier, F. G. van Zijderveld, and A. Bossers. "Prion Type-Dependent Deposition ofPRNPAllelic Products in Heterozygous Sheep." Journal of Virology 90, no. 2 (October 28, 2015): 805–12. http://dx.doi.org/10.1128/jvi.02316-15.
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ABSTRACTSusceptibility or resistance to prion infection in humans and animals depends on single prion protein (PrP) amino acid substitutions in the host, but the agent's modulating role has not been well investigated. Compared to disease incubation times in wild-type homozygous ARQ/ARQ (where each triplet represents the amino acids at codons 136, 154, and 171, respectively) sheep, scrapie susceptibility is reduced to near resistance in ARR/ARR animals while it is strongly enhanced in VRQ/VRQ carriers. Heterozygous ARR/VRQ animals exhibit delayed incubation periods. In bovine spongiform encephalopathy (BSE) infection, the polymorphism effect is quite different although the ARR allotype remains the least susceptible. In this study, PrP allotype composition in protease-resistant prion protein (PrPres) from brain of heterozygous ARR/VRQ scrapie-infected sheep was compared with that of BSE-infected sheep with a similar genotype. A triplex Western blotting technique was used to estimate the two allotype PrP fractions in PrPresmaterial from BSE-infected ARR/VRQ sheep. PrPresin BSE contained equimolar amounts of VRQ- and ARR-PrP, which contrasts with the excess (>95%) VRQ-PrP fraction found in PrP in scrapie. This is evidence that transmissible spongiform encephalopathy (TSE) agent properties alone, perhaps structural aspects of prions (such as PrP amino acid sequence variants and PrP conformational state), determine the polymorphic dependence of the PrPresaccumulation process in prion formation as well as the disease-associated phenotypic expressions in the host.IMPORTANCETransmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative and transmissible diseases caused by prions. Amino acid sequence variants of the prion protein (PrP) determine transmissibility in the hosts, as has been shown for classical scrapie in sheep. Each individual produces a separate PrP molecule from its two PrP gene copies. Heterozygous scrapie-infected sheep that produce two PrP variants associated with opposite scrapie susceptibilities (136V-PrP variant, high; 171R-PrP variant, very low) contain in their prion material over 95% of the 136V PrP variant. However, when these sheep are infected with prions from cattle (bovine spongiform encephalopathy [BSE]), both PrP variants occur in equal ratios. This shows that the infecting prion type determines the accumulating PrP variant ratio in the heterozygous host. While the host's PrP is considered a determining factor, these results emphasize that prion structure plays a role during host infection and that PrP variant involvement in prions of heterozygous carriers is a critical field for understanding prion formation.
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Nishida, Yuzo. "Elucidation of Endemic Neurodegenerative Diseases - a Commentary." Zeitschrift für Naturforschung C 58, no. 9-10 (October 1, 2003): 752–58. http://dx.doi.org/10.1515/znc-2003-9-1028.
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AbstractRecent investigations of scrapie, Creutzfeldt-Jakob disease (CJD), and chronic wasting disease (CWD) clusters in Iceland, Slovakia and Colorado, respectively, have indicated that the soil in these regions is low in copper and higher in manganese, and it has been well-known that patients of ALS or Parkinson’s disease were collectively found in the New Guinea and Papua islands, where the subterranean water (drinking water) contains much Al3+ and Mn2+ ions. Above facts suggest that these neurodegenerative diseases are closely related with the function of a metal ion.We have investigated the chemical functions of the metal ions in detail and established the unique mechanism of the oxygen activation by the transition metal ions such as iron and copper, and pointed out the notable difference in the mechanism among iron, aluminum and manganese ions. Based on these results, it has become apparent that the incorporation of Al(III) or Mn(II) in the cells induces the “iron-overload syndrome”, which is mainly due to the difference in an oxygen activation mechanism between the iron ion and Al(III) or the Mn(II) ion. This syndrome highly promotes formation of hydrogen peroxide, and hydrogen peroxide thus produced can be a main factor to cause serious damages to DNA and proteins (oxidative stress), yielding a copper(II)-or manganese(II)-peptide complex and its peroxide adduct, which are the serious agents to induce the structural changes from the normal prion protein (PrPC) to abnormal disease-causing isoforms, PrPSc, or the formation of PrP 27Ð30 (abnormal cleavage at site 90 of the prion protein).It seems reasonable to consider that the essential origin for the transmissible spongiform encephalopathies (TSEs) should be the incorporation and accumulation of Al(III) and Mn(II) ions in the cells, and the sudden and explosive increase of scrapie and bovine spongiform encephalopathy (BSE) in the last decade may be partially due to “acid rain”, because the acid rain makes Al(III) and Mn(II) ions soluble in the subterranean aquifers.
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Chesebro, Bruce. "Prion Protein and the Transmissible Spongiform Encephalopathy Diseases." Neuron 24, no. 3 (November 1999): 503–6. http://dx.doi.org/10.1016/s0896-6273(00)81105-8.
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Race, Richard E., Anne Raines, Thierry G. M. Baron, Michael W. Miller, Allen Jenny, and Elizabeth S. Williams. "Comparison of Abnormal Prion Protein Glycoform Patterns from Transmissible Spongiform Encephalopathy Agent-Infected Deer, Elk, Sheep, and Cattle." Journal of Virology 76, no. 23 (December 1, 2002): 12365–68. http://dx.doi.org/10.1128/jvi.76.23.12365-12368.2002.
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ABSTRACT Analysis of abnormal prion protein glycoform patterns from chronic wasting disease (CWD)-affected deer and elk, scrapie-affected sheep and cattle, and cattle with bovine spongiform encephalopathy failed to identify patterns capable of reliably distinguishing these transmissible spongiform encephalopathy diseases. However, PrP-res patterns sometimes differed among individual animals, suggesting infection by different or multiple CWD strains in some species.
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Heumüller, Stefanie-Elisabeth, Annika C. Hornberger, Alina S. Hebestreit, André Hossinger, and Ina M. Vorberg. "Propagation and Dissemination Strategies of Transmissible Spongiform Encephalopathy Agents in Mammalian Cells." International Journal of Molecular Sciences 23, no. 6 (March 8, 2022): 2909. http://dx.doi.org/10.3390/ijms23062909.
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Transmissible spongiform encephalopathies or prion disorders are fatal infectious diseases that cause characteristic spongiform degeneration in the central nervous system. The causative agent, the so-called prion, is an unconventional infectious agent that propagates by converting the host-encoded cellular prion protein PrP into ordered protein aggregates with infectious properties. Prions are devoid of coding nucleic acid and thus rely on the host cell machinery for propagation. While it is now established that, in addition to PrP, other cellular factors or processes determine the susceptibility of cell lines to prion infection, exact factors and cellular processes remain broadly obscure. Still, cellular models have uncovered important aspects of prion propagation and revealed intercellular dissemination strategies shared with other intracellular pathogens. Here, we summarize what we learned about the processes of prion invasion, intracellular replication and subsequent dissemination from ex vivo cell models.
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Murdoch, Brenda M., and Gordon K. Murdoch. "Genetics of Prion Disease in Cattle." Bioinformatics and Biology Insights 9S4 (January 2015): BBI.S29678. http://dx.doi.org/10.4137/bbi.s29678.
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Bovine spongiform encephalopathy (BSE) is a prion disease that is invariably fatal in cattle and has been implicated as a significant human health risk. As a transmissible disease of livestock, it has impacted food safety, production practices, global trade, and profitability. Genetic polymorphisms that alter the prion protein in humans and sheep are associated with transmissible spongiform encephalopathy susceptibility or resistance. In contrast, there is no strong evidence that nonsynonymous mutations in the bovine prion gene (PRNP) are associated with classical BSE (C-BSE) disease susceptibility, though two bovine PRNP insertion/deletion polymorphisms, in the putative region, are associated with susceptibility to C-BSE. However, these associations do not explain the full extent of BSE susceptibility, and loci outside of PRNP appear to be associated with disease incidence in some cattle populations. This article provides a review of the current state of genetic knowledge regarding prion diseases in cattle.
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Williams, J. L. "Genetics of transmissible spongiform encephalopathy susceptibility and the search for surrogate markers for infection." Australian Journal of Experimental Agriculture 44, no. 11 (2004): 1119. http://dx.doi.org/10.1071/ea03235.
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The transmissible spongiform encephalopathy diseases are unusual in that they can be sporadic or infectious, and that the infectious agent does not contain nucleic acids. Instead, infectivity is associated with a modified host-encoded protein referred to as a prion. During the course of disease, host encoded prion protein (PrP) is converted from the normal cellular form, PrPC, to a disease form, PrPSC/BSE, which is highly resistant to degradation by heat or proteinases. The occurrence of the sporadic form of transmissible spongiform encephalopathy disease in humans, as well as susceptibility to infection in humans and some animal species has been correlated with particular alleles of the host PrP gene. Scrapie has been endemic in sheep populations in many countries for over 100 years, with no apparent adverse effects on human health, however the occurrence of bovine spongiform encephalopathy in the mid 1980s in the United Kingdom and subsequently other countries has stimulated interest in the transmissible spongiform encephalopathy diseases. Bovine spongiform encephalopathy seems to have arisen from the recycling of ruminant offals, although it is not clear whether bovine spongiform encephalopathy was already endemic in the cattle population and this practice simply increased the incidence, or if the disease was newly introduced to cattle by transmission of scrapie from sheep. A new form of Creutzfeldt-Jacob disease that bares all the hallmarks of bovine spongiform encephalopathy was recently described in humans, suggesting that it arose from consumption of bovine spongiform encephalopathy-infected beef. Subsequent studies have demonstrated that transmissible spongiform encephalopathy disease can be experimentally transmitted between species and has alerted us to the potential risk of allowing scrapie to remain in the sheep population. In the United Kingdom, the sheep population is being PrP-genotyped and breeding stock selected from animals with genotypes that have been shown to be more resistant to scrapie. However, the resistant sheep genotypes may still harbour disease. There is no convincing evidence for PrP genotypes in cattle that are resistant to bovine spongiform encephalopathy. Work in cattle and mice has shown that there are loci other than PrP that influence the host response to a transmissible spongiform encephalopathy challenge. In order to monitor, and ultimately control, transmissible spongiform encephalopathy diseases in livestock it is important to identify markers for infection that are robust, appear early in infection and can be measured in an easily obtained sample, such as blood. We have developed a bovine ‘non-redundant’ cDNA set from brain to allow expression profiling using macro- and micro array technology. The identities of genes represented the in the non-redundant cDNAs set were assigned by oligo-nucleotide fingerprinting and have been confirmed by sequencing. This non-redundant cDNA set has been used to create a bovine array that is being used to examine expression in tissues from cattle during a time course of experimental bovine spongiform encephalopathy infection in order to identify genes with expression profiles that are altered following infection. Such genes may provide surrogate markers to detect transmissible spongiform encephalopathy infection during the early stages of disease. Ultimately knowledge of such genes may suggest targets for pharmacological intervention to arrest the disease process before the onset of the major neurological damage associated with the terminal stage of the disease.
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Takemura, K., M. Kahdre, D. Joseph, A. Yousef, and S. Sreevatsan. "An overview of transmissible spongiform encephalopathies." Animal Health Research Reviews 5, no. 2 (December 2004): 103–24. http://dx.doi.org/10.1079/ahr200494.
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AbstractTransmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative disorders of humans and animals associated with an accumulation of abnormal isoforms of prion protein (PrP) in nerve cells. The pathogenesis of TSEs involves conformational conversions of normal cellular PrP (PrPc) to abnormal isoforms of PrP (PrPSc). While the protein-only hypothesis has been widely accepted as a causal mechanism of prion diseases, evidence from more recent research suggests a possible involvement of other cellular component(s) or as yet undefined infectious agent(s) in PrP pathogenesis. Although the underlying mechanisms of PrP strain variation and the determinants of interspecies transmissibility have not been fully elucidated, biochemical and molecular findings indicate that bovine spongiform encephalopathy in cattle and new-variant Creutzfeldt–Jakob disease in humans are caused by indistinguishable etiological agent(s). Cumulative evidence suggests that there may be risks of humans acquiring TSEs via a variety of exposures to infected material. The development of highly precise ligands is warranted to detect and differentiate strains, allelic variants and infectious isoforms of these PrPs. This article describes the general features of TSEs and PrP, the current understanding of their pathogenesis, recent advances in prion disease diagnostics, and PrP inactivation.
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Hamir, A. N., J. M. Miller, R. A. Kunkle, S. M. Hall, and J. A. Richt. "Susceptibility of Cattle to First-passage Intracerebral Inoculation with Chronic Wasting Disease Agent from White-tailed Deer." Veterinary Pathology 44, no. 4 (July 2007): 487–93. http://dx.doi.org/10.1354/vp.44-4-487.
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Fourteen, 3-month-old calves were intracerebrally inoculated with the agent of chronic wasting disease (CWD) from white-tailed deer (CWDwtd) to compare the clinical signs and neuropathologic findings with those of certain other transmissible spongiform encephalopathies (TSE, prion diseases) that have been shown to be experimentally transmissible to cattle (sheep scrapie, CWD of mule deer [CWDmd], bovine spongiform encephalopathy [BSE], and transmissible mink encephalopathy). Two uninoculated calves served as controls. Within 26 months postinoculation (MPI), 12 inoculated calves had lost considerable weight and eventually became recumbent. Of the 12 inoculated calves, 11 (92%) developed clinical signs. Although spongiform encephalopathy (SE) was not observed, abnormal prion protein (PrPd) was detected by immunohistochemistry (IHC) and Western blot (WB) in central nervous system tissues. The absence of SE with presence of PrPd has also been observed when other TSE agents (scrapie and CWDmd) were similarly inoculated into cattle. The IHC and WB findings suggest that the diagnostic techniques currently used to confirm BSE would detect CWDwtd in cattle, should it occur naturally. Also, the absence of SE and a distinctive IHC pattern of CWDwtd and CWDmd in cattle suggests that it should be possible to distinguish these conditions from other TSEs that have been experimentally transmitted to cattle.
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Race, Richard E., and Gregory J. Raymond. "Inactivation of Transmissible Spongiform Encephalopathy (Prion) Agents by Environ LpH." Journal of Virology 78, no. 4 (February 15, 2004): 2164–65. http://dx.doi.org/10.1128/jvi.78.4.2164-2165.2004.
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ABSTRACT Agents causing transmissible spongiform encephalopathy (TSE) diseases are resistant to inactivation by several conventional decontamination methods. Using an animal bioassay, we compared the TSE agent disinfectant efficacy of a commercially available product referred to alternatively as LpH-SE, LpH-AG, or LpH-st to that of a similarly named but differently formulated product, Environ LpH, which was found to be an effective TSE agent disinfectant in a previous study. Here, we found LpH-SE to be at least 104-fold to 105-fold less effective than Environ LpH.
Dissertations / Theses on the topic "Prion, copper, Transmissible spongiform encephalopathy"
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Dobie, Karen Louise. "Investigating the relationship between abnormal prion protein (PrPSc) and the transmissible spongiform encephalopathy (TSE) infectious agent." Thesis, University of Edinburgh, 2013. http://hdl.handle.net/1842/8107.
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Transmissible spongiform encephalopathies (TSEs) are a group of fatal, neurodegenerative diseases that can affect both humans and animals. TSEs can be sporadic, familial, or acquired diseases. The prion hypothesis states that a misfolded form of the host glycoprotein, PrPC, acts as the infectious agent in TSE disease. The misfolded form, PrPSc, is increased in β-sheet content, detergent insoluble and partially resistant to proteinase K (PK) digestion. Based on the prion hypothesis, most current post-mortem diagnostic tests rely on the presence of PrPSc as indicative of TSE disease. However, recently experimental cases of TSE disease have been identified where no PrPSc deposition is evident. One example of this is a murine transgenic model of Gerstmann Sträussler Scheinker (GSS) disease. GSS is a familial TSE disease, caused by a number of different mutations in human PrP including a point mutation from proline to leucine at residue 102. A murine model of GSS disease, produced through gene-targeting, contains the same point mutation at the equivalent residue, 101, in murine PrP. These mice do not develop spontaneous disease during their lifespan, but when inoculated intra-cerebrally with either human P102L GSS (101LL/GSS) or hamster 263K scrapie (101LL/263K); develop a clinical disease and vacuolar TSE-related pathology. Upon biochemical and immunohistochemical analysis, the brain tissues of these clinically ill mice contain little or no detectable PrPSc. However titration experiments have previously shown infectivity titres of 107-109IU/g of brain tissue. Standard PK digestion (at 37°C), NaPTA precipitation and isolation of PrPSc through detergent insolubility and differential centrifugation all confirmed the observation of little or no detectable PK-resistant PrP (PrP-res) in the 101LL/GSS and 101LL/263K brain tissues, despite the high levels of TSE infectivity. The presence of PrPSc and/or TSE infectivity in the spleen during disease pathogenesis is dependent upon TSE agent strain and host species. Previous studies utilising wild-type mice infected with ME7, have shown that the levels of infectivity observed in spleen tissue are 2- 3log10 lower than those observed in the brain tissue of the same mice. However, experiments conducted as part of this thesis showed that sub-passage of both the brain and spleen tissue from clinically ill 101LL/GSS and 101LL/263K mice into 101LL mice by intra-cerebral inoculation result in short incubation periods, indicating that infectivity levels were similarly high in both tissues. Biochemical analysis of the primary spleen tissue identified the presence of PrP-res, albeit at lower levels than those observed in wild-type spleens infected with a standard laboratory TSE strain, ME7 or 79A. However, the presence of PrP-res indicates that the spleen has a role in disease pathogenesis, which will require further investigation. Additionally, the spleen tissue maintains the discrepancy between PrP-res and TSE infectivity that is observed in the brain tissue of these models and further questions the prion hypothesis. As little or no PrP-res was detectable in the brain tissues of 101LL/GSS and 101LL/263K mice by standard biochemical and immunohistochemical techniques, it was hypothesised that an in vitro amplification technique, protein misfolding cyclic amplification (PMCA) could amplify PrPSc to detectable levels. A series of optimisation experiments were performed to produce a reliable positive control for amplification of mouse PrPSc from a standard laboratory mouse TSE strain, 79A or ME7, with a normal wild-type mouse brain homogenate substrate. While a wide range of technical and experimental conditions were investigated, consistent and reproducible amplification of mouse PrPSc was not achieved and therefore amplification of PrPSc from 101LL/GSS and 101LL/263K tissues could not be performed as interpretation of results would be complicated without the presence of a positive control. Previous research has shown that while other commercial assays, e.g. TeSeE (BioRad), identified tissues from these models as borderline positive or negative for TSE disease, one TSE diagnostic assay, the IDEXX HerdChek kit, that utilises the Seprion ligand, identified both the brain and spleen tissue from 101LL/GSS and 101LL/263K clinical mice as positive for TSE disease. In order to identify if TSE infectivity is associated with the target of the Seprion ligand, brain tissue homogenates from 101LL/GSS, 101LL/263K and a positive control wild-type/79A homogenate were depleted of the Seprion ligand target utilising a PAD-beads kit (Microsens Biotechnologies), which incorporates the Seprion ligand as the capture agent, in combination with magnetic beads. Upon inoculation, a single depletion of the homogenates produced no significant reduction in incubation period to clinical disease in either the depleted homogenates or the wash buffers produced, in comparison to a non-depleted brain homogenate. This result indicates that a single depletion with the Seprion ligand, did not remove enough of the aggregated protein to significantly alter the level of infectivity in the depleted homogenate and that any infectious agent, which was initially bound to the Seprion ligand due to non-specific interactions, was then released during the wash steps of the procedure. Proteomic differences between all components produced during a single depletion of an infected brain homogenate, wild-type/79A, or a normal uninfected brain homogenate were assessed to potentially identify the target of the Seprion ligand. In conclusion, these murine models of TSE disease, 101LL/GSS and 101LL/263K, which contain both high infectivity levels with little or no PrP-res in the brain tissue and similar high levels of infectivity with low levels of PrP-res in the spleen, questions the accepted correlation between levels of infectivity and PrP-res or PrPSc as proposed by the prion hypothesis. It is hypothesised that either an alternative form of PrP, which has not yet been identified is the infectious agent in these disease models, or that the TSE infectious agent is a component which associates with PrPSc rather than being PrPSc itself. The eventual identification of the infectious agent present in these unusual disease models will increase our understanding of these diseases, potentially offer improved diagnostics for infectivity, and perhaps identify novel therapeutic targets.
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Bishop, Matthew T. "Role of PRNP codon 129 genotype in defining strain transmission properties of human transmissible spongiform encephalopathy." Thesis, University of Edinburgh, 2009. http://hdl.handle.net/1842/4236.
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The human prion protein (PrP) gene (PRNP) codon 129 (M/V) polymorphism is a susceptibility factor for variant Creutzfeldt-Jakob Disease (vCJD) and a major determinant of clinico-pathological phenotype in sporadic CJD. The role of codon 129 in defining susceptibility and strain transmission properties has been investigated in three lines of transgenic mice that express human PrP. The human PRNP gene has directly replaced the murine version, by gene targeting, and variation at codon 129 has given the three genotype lines (HuMM, HuMV, and HuVV). The genetics of these three mouse lines are otherwise identical, and therefore differences in transmission properties can be directly attributable to the codon 129 genotype. vCJD inoculation has shown that all three codon 129 genotype mice are susceptible with a ranking of transmission efficiency of HuMM>HuMV>HuVV. HuMM mice develop the most widespread neuropathology with features similar to human vCJD. Subclinical infection was noted in each mouse line. These data suggest that the vCJD strain is transmissible to humans of each of the three codon 129 genotypes, implying that non-MM cases of human infection with bovine spongiform encephalopathy (BSE) may exist but with long subclinical incubation periods. Inoculation of material from blood transfusion associated vCJD showed no change in transmission properties suggesting that the threat of a future epidemic of human-to-human vCJD infection has not been increased by adaptation of the vCJD strain. However the route of infection, for example via blood transfusion or surgery, may be more efficient that the original oral route of BSE infection. sCJD is classified into six subgroups according to clinico-pathological features, and defined by codon 129 genotype and electrophoretic mobility type (1 or 2) of disease associated PrPSc (MM1, MM2, MV1, MV2, VV1, VV2). Typical cases from each subgroup have shown specific transmission properties suggesting that the subgrouping is defining separate disease strains. The commonest subgroup (MM1) was the most transmissible and the HuVV mouse line the most susceptible host. These data outline the transmission risk from all sCJD types to recipients of each codon 129 genotype should an infection event occur, and show the significant role of recipient codon 129 genotype in defining the clinical or subclinical state and the success or failure of transmission. This is important for determining individual risk following known exposure, and for modelling the potential of iatrogenic infection from sCJD patients.
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CORDA, ERICA. "TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES (TSES): EXPERIMENTAL APPROACHES TO PATHOGENESIS, THERAPY AND PREVENTION IN ANIMAL MODELS." Doctoral thesis, Università degli Studi di Milano, 2012. http://hdl.handle.net/2434/169556.
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Prion diseases are perhaps the most mysterious and peculiar diseases in nature. These diseases do not rely on the general dogmas of modern biology, seen in other infectious diseases caused by conventional pathogens, such as viruses and bacteria. On the contrary, their infectious agent is an unconventional proteinaceous pathogen, termed prion, that lacks functional nucleic acids. Prion diseases are also known as Transmissible Spongiform Encephalopathies (TSEs), since the diseases are transmissible from one host to another and manifest a spongiform appearance as result of the destruction of brain tissue during a long incubation period. Prion diseases include Creutzfeldt-Jakob disease in humans, bovine spongiform encephalopathy (BSE, “mad cow disease”) in ruminants, scrapie in sheep and goats and chronic wasting disease in deer and elks. As demonstrated in the BSE outbreak and its transmission to humans, the onset of diseases is not limited to a certain species but can be transmissible from one host species to another. Such a striking nature of prions has generated huge concerns in public health and attracted serious attention in the scientific communities.
To date, the potential transmission of prions to human has not been alleviated and TSEs still have no reliable preclinical screening tests and effective treatments.
This doctoral thesis deals widely with the prion diseases, from epidemiology to pathogenesis, from diagnosis to therapy and prevention. Moreover it describes in detail three experimental projects aimed to clarify different aspects of TSEs. In all of them wild-type mouse bioassays are used, as they are the gold standard for assessing the biological properties of prions.
The goal of the first study was to assess the therapeutic and/or preventive activity on TSEs of the chronic administration of a new γ-secretase modulator. The second research investigated the ability to identify BSE in presence of scrapie. The third project was aimed to study the effects induced by chronic administration of lipid enriched/depleted specific diets on the pathogenesis of prion diseases.
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Brown, Karen L. "Influence of the immune system on peripherally acquired transmissible spongiform encephalopathy infection with special reference to the role of the follicular dendritic cell." Thesis, University of Edinburgh, 2009. http://hdl.handle.net/1842/4376.
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The Transmissible Spongiform Encephalopathies (TSEs) or “prion” diseases are a group of fatal neurodegenerative diseases the aetiology of which is not fully understood. These diseases are characterised by a number of pathological changes in the central nervous system (CNS) including; vacuolation of the neuropil, gliosis and deposition of PrPSc; the abnormal form of the host glycoprotein PrP. Although the major pathology in these diseases is associated with the CNS the immune system is central to the pathogenesis of many natural and experimental TSEs including natural scrapie in sheep, chronic wasting disease in free ranging and captive deer and variant CJD (vCJD) in humans. Unlike many infectious diseases where deficiencies in immune function are opportunistic for the invading pathogen a competent immune system is required for efficient TSE infection via peripheral routes. As infection of the lymphoid tissues in many TSEs can occur many months before the detection of infectivity in the CNS, the determination of those cells in the lymphoid system has been the focus of much research and a number of studies now point towards the importance of the follicular dendritic cell (FDC), a long-lived radio resistant cell, in TSE pathogenesis. The involvement of FDCs in peripheral TSE pathogenesis relates to the inability of ionising radiation to influence pathogenesis, the association of PrP protein with FDCs in both uninfected and infected lymphoid tissues, and the demonstration that TSE pathogenesis is severely impaired in mice devoid of these cells. The aims of this thesis were to further understand the role of FDCs in the pathogenesis of a range of mouse-adapted experimental TSE strains and to determine if peripherally acquired TSE infections are influenced by host age or by stimulation of the immune system. Using chimaeric mouse models where a mismatch in the expression of PrP protein between FDCs and lymphoid/myeloid cells was produced, further evidence for a critical role for in the pathogenesis of the ME7 TSE strain was produced. Although these findings produced strong evidence that FDCs were important for the ME7 strain the possibility that different TSE strains may target different cell types in the peripheral lymphoid system was explored using a range of mice with specific immunological defects. Infection of these mice with several experimental TSE strains showed that the presence of mature FDCs was also important for the pathogenesis of the strains tested. Clinical cases of vCJD have been confined almost exclusively to young adults, although the reasons behind this apparent age-related susceptibility are not fully understood. The capacity of the immune system to mediate immune responses to pathogens declines with age as a result of impaired lymphocyte and FDC function. As FDCs are critically involved in the pathogenesis of many TSEs, including vCJD, it was hypothesised that an aging immune system may impair disease pathogenesis. Peripheral infection of senescent mice failed to produce clinical disease during lifespan, although evidence of disease transmission, was detected in a proportion of aged mice. These findings demonstrate that this inefficient disease transmission, as a consequence of age, may lead to considerable levels of sub-clinical disease within the population. Finally the influence of immune system stimulation, by the generation of a humoral immune response, on peripheral TSE pathogenesis was investigated. These findings demonstrated that immunisation can influence pathogenesis, but only during the early stages of infection prior to spread to the CNS. These data imply that modulation of the immune system does not alter TSE pathogenesis once disease has been initiated in the CNS. Finally, these studies have found some preliminary evidence that TSE infection may induce FDC activation suggesting that TSE infection may influence the immune response. Together, these data show that a functional immune system and specifically, the presence of mature FDCs, are central to the pathogenesis of peripherally acquired TSE infections.
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Boerner, Susann. "Probing reaction conditions and cofactors of conformational prion protein changes underlying the autocatalytic self-propagation of different prion strains." Doctoral thesis, Humboldt-Universität zu Berlin, Lebenswissenschaftliche Fakultät, 2014. http://dx.doi.org/10.18452/17003.
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Prionen sind das infektiöse Agens transmissibler spongiformer Enzephalopathien von Tieren und Menschen. Prionen bestehen hauptsächlich aus einer abnormal gefalteten und aggregierten Isoform des zellulären Prionproteins (PrP). Die Replikation von Prionen findet mutmaßlich durch keiminduzierte Polymerisation des Prionproteins statt. Es existieren verschiedene Prionstämme, die unterschiedliche Eigenschaften aufweisen, aber vom selben zellulären Prionprotein abstammen können. Neben PrP scheinen Kofaktormoleküle an der Prionreplikation beteiligt zu sein. Weiterhin wird angenommen, dass Kofaktoren bei der Definition von Stammeigenschaften beteiligt sind, sowie ein Einfluss auf die Infektiosität von Prionen besteht. In dieser Arbeit wurden die Auswirkungen verschiedener Kofaktoren auf die Replikation von vier Hamster-adaptierten Prionstämmen in vitro mittels der Methode der „Protein Misfolding Cyclic Amplification“ (PMCA) untersucht. Es wurden stammabhängige Unterschiede bezüglich der Anforderungen an die Replikationsbedingungen in der PMCA, sowie Kofaktor-Selektivitäten festgestellt. Der Einfluss von Kofaktoren wurde durch den Vergleich ausgewählter biologischer, biochemischer und biophysikalischer Eigenschaften von in vitro erzeugten PMCA Produkten (PrPres) mit denen nativer Prionkeime untersucht. Es zeigte sich, dass Kofaktoren Stammeigenschaften, wie die biologische Keimaktivität in primären Gliazellkulturen und biochemische Eigenschaften, wie die Migration in SDS-Gelen, beeinflussen können. Um festzustellen, ob unterschiedliche Kofaktorbedingungen während der PMCA messbare Veränderungen der Proteinkonformation hervorrufen, wurde PMCA generiertes PrPres mittels FT-IR Spektroskopie in einer Pilotstudie charakterisiert. Erste Befunde zeigten spektrale Unterschiede zwischen den Proteinkeimen und deren PMCA Produkten bei allen Stämmen, unabhängig von den Kofaktorbedingungen.Prions are the causative agent of transmissible spongiform encephalopathies in animals and humans such as scrapie, bovine spongiform encephalopathy (BSE) and Creutzfeldt-Jakob disease (CJD). Prions are thought to be composed essentially of a misfolded and aberrantly aggregated isoform of the cellular prion protein (PrP) and to replicate by seeded PrP polymerization. Prions may exist in the form of distinct strains that differ in their phenotypic characteristics although they are derived from the same cellular prion protein. Cofactor molecules other than PrP may be involved in prion replication and may be a determinant of strain properties. Furthermore, cofactors may also be required for conveying infectivity. The present study examined the effects of different cofactor molecules on the replication efficacy of four hamster adapted prion agents using the method of serial protein misfolding cyclic amplification (PMCA) as in vitro assay for PrP misfolding and aggregation. The study revealed strain dependent differences of PMCA conditions and cofactors required for efficient in vitro replication. The impact of cofactors was assessed by comparative analyses of selected biological, biochemical and biophysical properties of PMCA products (PrPres) and native prion seeds. The biological seeding activity as monitored in a primary hamster glial cell assay, and biochemical properties such as electrophoretic migration in SDS-gels, were affected differently by different cofactors. In order to define the impact of putative cofactors on the molecular conversion of PrP in more detail, changes in the spatial structure associated with different cofactor molecule conditions during amplification of PrPres in PMCA was monitored by Fourier transform-infrared (FT-IR) spectroscopic analysis. Largely preliminary data revealed spectral differences between native prion seeds and progeny PMCA generated PrPres for all prion strains, but no variations due to different cofactor conditions.
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Borges, Álvarez Marta. "Establiment de metodologia analítica per a la purificació, separació i caracterització de biomarcadors proteics de malalties neurodegeneratives." Doctoral thesis, Universitat de Barcelona, 2012. http://hdl.handle.net/10803/119540.
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En aquesta tesi doctoral, s’ha desenvolupat metodologia analítica per a la purificació, separació i caracterització de prió cel•lular (PrPC) i superòxid dismutasa (SOD-1), dues proteïnes relacionades amb les Encefalopaties Espongiformes Transmissibles (TSEs) i l’Esclerosi Lateral Amiotròfica (ALS), respectivament. Les TSEs es caracteritzen per l’acumulació de la forma patològica del PrPC (PrPSc) al cervell dels animals afectats, mentre que a l’ALS s’observa la formació d’agregats de SOD-1. Avui dia, encara es desconeixen els factors que inicien i regulen les interaccions que condueixen a la formació d’agregats proteics en moltes malalties neurodegeneratives. Alguns autors suggereixen mecanismes basats en els canvis estructurals que s’observen entre la proteïna nativa i la patològica, que estan relacionats amb la conformació, la seqüència d’aminoàcids, els metalls o les modificacions post-transduccionals. En proteïnes oligomèriques com la SOD-1, també s’ha considerat la dissociació dels oligòmers fins a monòmers abans de l’agregació. És doncs necessari millorar el coneixement de l’estructura d’aquestes proteïnes i aprofundir en els mecanismes que governen l’agregació.
En aquest treball es proposa una estratègia de purificació per recuperar de manera eficient PrPC de cervell boví emprant mètodes de purificació convencionals no immuniquímics i western blot (WB) per detectar la presència PrPC en les diferents etapes. Tot seguit s’estudia exhaustivament la separació i caracterització de la SOD-1 mitjançant electroforesi capil•lar acoblada a l’espectrometria de masses amb analitzadors de trampa iònica i de temps de vol (CE-IT-MS i CE-TOF-MS), espectrometria de masses amb font d’ionització per desorció amb làser assistida per una matriu i analitzador de temps de vol (MALDI-TOF-MS) i espectrometria de masses de mobilitat iònica amb font d’ionització per nano-electrosprai (n-ESI-IM-MS). Els estudis amb SOD-1 purificada a partir de mostres de sang d’individus sans i pacients amb ALS han permès obtenir algunes conclusions preliminars interessants sobre els canvis estructurals en la proteïna associats a la malaltia.In this thesis, we developed an analytical method for the purification, separation and characterization of cellular prion (PrPC) and superoxide dismutase (SOD-1), two proteins related to Transmissible Spongiform Encephalopathies (TSEs) and the Amyotrophic Lateral Sclerosis (ALS), respectively. The TSEs are characterized by the accumulation of the pathological form of PrPC (PrPSc) in the brain of affected animals, whereas in ALS it is observed the formation of aggregates of SOD-1. Today, factors that initiate and regulate the interactions that lead to the formation of protein aggregates in many neurodegenerative diseases are still unknown. Some authors suggest mechanisms based on the structural changes observed between the native and the pathology protein which cold be related with the conformation, the amino acid sequence, metals or post-translational modifications. In oligomeric proteins such as SOD-1, the dissociation of oligomers to monomers before aggregation it is also considered. So, it is crucial to increase the knowledge of the structure of these proteins and the mechanisms that govern its aggregation for understanding the disease development. This paper proposes a strategy for having an efficient recovery in the purification of bovine brain PrPC using conventional purification methods that not involves immunochemical procedures. The presence of PrPC was checked at different stages by western blot (WB). Then, the separation and characterization of the SOD-1 by capillary electrophoresis coupled to mass spectrometry with ion trap and time of flight analyzers (CE-IT-MS and CE-TOF-MS), matrix-assisted laser desorption/ionization with a time of flight mass analyzer (MALDI-TOF-MS) and ion mobility mass spectrometry with power nano-electrospray ionization source (n-ESI-IM-MS) was studied. The comparison of purified SOD-1 from blood samples of healthy individuals and patients with ALS have yielded some preliminary interesting conclusions about structural changes in the protein associated with cold be related with the disease.
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Legleiter, Leon R. "The relationship between copper, manganese, and bovine brain prion proteins: implications for trace mineral nutrition and bovine spongiform encephalopathy /." 2006. http://www.lib.ncsu.edu/theses/available/etd-11032006-085510/unrestricted/etd.pdf.
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Spassov, Sashko G. [Verfasser]. "Investigation of scrapie associated prion protein PrP27-30 and strain differentiation of transmissible spongiform encephalopathy by Fourier transform infrared spectroscopy techniques / vorgelegt von Sashko Georgiev Spassov." 2006. http://d-nb.info/980867703/34.
Full textBooks on the topic "Prion, copper, Transmissible spongiform encephalopathy"
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Mad cows and cannibals: A guide to the transmissible spongiform encephalopathies. Upper Saddle River, NJ: Pearson/Prentice Hall, 2004.
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International Symposium on Transmissible Subacute Spongiform Encephalopathies: Prion Diseases (3rd 1996 Paris, France). Transmissible subacute spongiform encephalopathies: Prion diseases : IIIrd International Symposium on Transmissible Subacute Spongiform Encephalopathies: Prion Diseases, 18-20 March 1996, Val-de-Grâce, Paris, France. Amsterdam: Elsevier, 1996.
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Great Britain. Advisory Committee on Dangerous Pathogens., ed. Precautions for work with human and animal transmissible spongiform encephalopathies. London: HMSO, 1994.
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Ministry of Agriculture, Fisheries and Food. Strategy for research and development relating to the animal health aspects of transmissible spongiform encephalopathies. [London]: GB MAFF, 1998.
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International Meeting on Transmissible Spongiform Encephalopathies - Impact on Animal and Human Health. International Meeting on Transmissible Spongiform Encephalopathies - Impact on Animal and Human Health: Proceedings of a meeting held at the Kongresshaus, Stadthalle, Heidelberg (Germany), June 23-24, 1992. Basel: Karger, 1993.
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Kate, Brown. Meeting of the OIE Ad Hoc Research Group on Transmissible Spongiform Encephalopathies, Paris, 8-10 October, 1996: United Kingdom research review. London: Great Britain, Ministry of Agriculture, Fisheries and Food, 1996.
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World Health Organization (WHO). Report of a WHO consultation on medicinal and other products in relation to human and other animal transmissible spongiform encephalopathies, with the participation of the Office International des Epizooties (OIE), Geneva, Switzerland, 24-26 March, 1997. Geneva: WHO, 1997.
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F, Brown, and International Association of Biological Standardization., eds. Transmissible spongiform encephalopathies: Impact on animal and human health : proceedings of a meeting held at the Kongresshaus, Stadthalle, Heidelberg (Germany), June 23-24, 1992. Basel: Karger, 1993.
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Transmissible Spongiform Enecephalopathies: Impact on Animal and Human Health (Developments in Biologicals). S. Karger AG (Switzerland), 1993.
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WHO Guidelines on Tissue Infectivity Distribution in Transmissible Spongiform Encephalopathies. World Health Organization, 2006.
Find full textBook chapters on the topic "Prion, copper, Transmissible spongiform encephalopathy"
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Silveira, J. R., B. Caughey, and G. S. Baron. "Prion Protein and the Molecular Features of Transmissible Spongiform Encephalopathy Agents." In Current Topics in Microbiology and Immunology, 1–50. Berlin, Heidelberg: Springer Berlin Heidelberg, 2004. http://dx.doi.org/10.1007/978-3-662-08441-0_1.
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Raymond, Gregory J., and Joëlle Chabry. "Purification of the Pathological Isoform of Prion Protein (PrPSc or PrPres) from Transmissible Spongiform Encephalopathy-affected Brain Tissue." In Techniques in Prion Research, 16–26. Basel: Birkhäuser Basel, 2004. http://dx.doi.org/10.1007/978-3-0348-7949-1_3.
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Brown, P. "Transmissible spongiform encephalopathy (prion disease)." In Foodborne Pathogens, 1119–39. Elsevier, 2009. http://dx.doi.org/10.1533/9781845696337.3.1119.
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Singh, Sujatha, and Mahendra Pal. "Bovine Spongiform Encephalopathy—A Transmissible Prion Based Disease." In Reference Module in Food Science. Elsevier, 2023. http://dx.doi.org/10.1016/b978-0-12-822521-9.00083-6.
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Ironside, James W., Matthew P. Frosch, and Bernardino Ghetti. "Human Prion Diseases." In Escourolle and Poirier's Manual of Basic Neuropathology, 149–60. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199929054.003.0006.
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This chapter describes and illustrates the neuropathology of prion diseases, also known as transmissible spongiform encephalopathies. These diseases are characterized pathologically by varying combinations of spongiform change, neuronal loss, reactive gliosis, and prion protein (PrP) deposition. The morphologic pattern depends on the etiology of the disease and the genotype of the patient. Different clinicopathological phenotypes of sporadic Creutzfeldt-Jakob disease (CJD) have been described depending on the PRNP codon 129 genotype and the PrP isotype. A novel form known as variably protease-sensitive prionopathy has been recently identified. Familial prion diseases include familial CJD, Gerstmann-Sträussler-Scheinker disease, and fatal familial insomnia. Over 40 different PRNP mutations have been identified. Acquired prion diseases include Kuru; iatrogenic CJD, particularly in recipients of contaminated human pituitary hormone, and variant CJD, which seems closely related to bovine spongiform encephalopathy.
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Mead, Simon, and R. G. Will. "Human prion diseases." In Oxford Textbook of Medicine, edited by Christopher Kennard, 6109–19. Oxford University Press, 2020. http://dx.doi.org/10.1093/med/9780198746690.003.0599.
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Prion protein (for proteinacious infectious particle) is a membrane-associated glycoprotein present in all mammalian species. Its normal function is unknown, but in prion diseases (also known as transmissible spongiform encephalopathies) a misfolded polymer form of the protein, partially resistant to protease digestion, is deposited in the brain and associated—typically after long incubation periods—with neuronal dysfunction and death. Prion diseases have become the subject of intense scientific and public interest because they are caused by a biologically distinct disease mechanism and because of the implications for public health following the identification of a new human prion disease, variant Creutzfeldt–Jakob disease (vCJD), and the evidence that it is caused by the transmission to humans of a cattle prion disease, bovine spongiform encephalopathy (BSE).
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Collinge, John. "Prion disease." In New Oxford Textbook of Psychiatry, 351–61. Oxford University Press, 2012. http://dx.doi.org/10.1093/med/9780199696758.003.0044.
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The human prion diseases, also known as the subacute spongiform encephalopathies, have been traditionally classified into Creutzfeldt–Jakob disease (CJD), Gerstmann–Sträussler syndrome (GSS) (also known as Gerstmann–Sträussler–Scheinker disease), and kuru. Although rare, affecting about 1–2 per million worldwide per annum, remarkable attention has been recently focused on these diseases. This is because of the unique biology of the transmissible agent or prion, and also because bovine spongiform encephalopathy (BSE), an epidemic bovine prion disease, appears to have transmitted to humans as variant CJD (vCJD), opening the possibility of a significant threat to public health through dietary exposure to infected tissues. The transmissibility of the human diseases was demonstrated with the transmission, by intracerebral inoculation with brain homogenates into chimpanzees, of first kuru and then CJD in 1966 and 1968, respectively. Transmission of GSS followed in 1981. The prototypic prion disease is scrapie, a naturally occurring disease of sheep and goats, which has been recognized in Europe for over 200 years and which is present in the sheep flocks of many countries. Scrapie was demonstrated to be transmissible by inoculation in 1936 and the recognition that kuru, and then CJD, resembled scrapie in its histopathological appearances led to the suggestion that these diseases may also be transmissible. Kuru reached epidemic proportions amongst the Fore linguistic group in the Eastern Highlands of Papua New Guinea and was transmitted by ritual cannibalism. Since the cessation of cannibalism in the 1950s the disease has declined but a few cases still occur as a result of the long incubation periods in this condition, which may exceed 50 years. The term Creutzfeldt–Jakob disease was introduced by Spielmeyer in 1922 bringing together the case reports published by Creutzfeldt and Jakob. Several of these cases would not meet modern diagnostic criteria for CJD and indeed it was not until the demonstration of transmissibility allowed diagnostic criteria to be reassessed and refined that a clear diagnostic entity developed. All these diseases share common histopathological features; the classical triad of spongiform vacuolation (affecting any part of the cerebral grey matter), astrocytic proliferation, and neuronal loss, may be accompanied by the deposition of amyloid plaques.