Publications
| Title | Abstract | Year Filter | PMID(sorted descending) Filter |
|---|
| prp genotype: a flock-level risk factor for scrapie? | previous epidemiological studies of risk factors for classical scrapie at flock level have identified a variety of management and purchase related variables, along with increased flock size and, in some cases, breed effects. although known as a risk factor at the individual animal level, prp genotype frequencies at flock level have not yet been studied. in an unmatched case-control study, three measures of flock-level prion protein (prp) frequency estimates were investigated with respect to the ... | 2009 | 19783057 |
| repetitive immunization enhances the susceptibility of mice to peripherally administered prions. | the susceptibility of humans and animals to prion infections is determined by the virulence of the infectious agent, by genetic modifiers, and by hitherto unknown host and environmental risk factors. while little is known about the latter two, the activation state of the immune system was surmised to influence prion susceptibility. here we administered prions to mice that were repeatedly immunized by two initial injections of cpg oligodeoxynucleotides followed by repeated injections of bovine se ... | 2009 | 19779609 |
| the role of gpi-anchored prp c in mediating the neurotoxic effect of scrapie prions in neurons. | there are two central phenomena in prion disease: prion replication and prion neurotoxicity. underlying them both is the conversion of a host-encoded ubiquitously expressed protein, prion protein (prp(c)), into a partially-protease resistant isoform, prp(sc), which accumulates in the brain. prp(sc) is associated with both pathology and infectivity. in the absence of prp(c), prp(sc) cannot be generated and prp-null mice do not propagate infectivity or develop pathology on infection with scrapie. ... | 2010 | 19767655 |
| targeting of the prion protein to the cytosol: mechanisms and consequences. | prion diseases are characterized by the conformational transition of the cellular prion protein (prp(c)) into an aberrant protein conformer, designated scrapie-prion protein (prp(sc)). a causal link between protein misfolding and neurodegeneration has been established for a variety of neurodegenerative disease, such as alzheimer's disease, parkinson's disease and polyglutamine diseases, but there is an ongoing debate about the nature of the neurotoxic species and how non-native conformers can da ... | 2010 | 19767654 |
| prion protein and metal interaction: physiological and pathological implications. | metal induced free radicals are important mediators of neurotoxicity in several neurodegenerative conditions such as alzheimer's disease, parkinson's disease, and huntington's disease. similar evidence is now emerging for prion diseases, a group of neurodegenerative disorders of humans and animals. the main pathogenic agent in all prion disorders is prp-scrapie (prp(sc)), a beta-sheet rich isoform of a normal cell surface glycoprotein known as the prion protein (prp(c)). deposits of prp(sc) in t ... | 2010 | 19767653 |
| transgenic mice expressing porcine prion protein resistant to classical scrapie but susceptible to sheep bovine spongiform encephalopathy and atypical scrapie. | how susceptible pigs are to infection with sheep prions is unknown. we show, through transmission experiments in transgenic mice expressing porcine prion protein (prp), that the susceptibility of this mouse model to bovine spongiform encephalopathy (bse) can be enhanced after its passage in arq sheep, indicating that the pathogenicity of the bse agent is modified after passage in sheep. transgenic mice expressing porcine prp were, nevertheless, completely resistant to infection with a broad pane ... | 2009 | 19751582 |
| asymptomatic deer excrete infectious prions in faeces. | infectious prion diseases-scrapie of sheep and chronic wasting disease (cwd) of several species in the deer family-are transmitted naturally within affected host populations. although several possible sources of contagion have been identified in excretions and secretions from symptomatic animals, the biological importance of these sources in sustaining epidemics remains unclear. here we show that asymptomatic cwd-infected mule deer (odocoileus hemionus) excrete cwd prions in their faeces long be ... | 2009 | 19741608 |
| detection of prpsc in blood from sheep infected with the scrapie and bovine spongiform encephalopathy agents. | the role of blood in the iatrogenic transmission of transmissible spongiform encephalopathy (tse) or prion disease has become an increasing concern since the reports of variant creutzfeldt-jakob disease (vcjd) transmission through blood transfusion from humans with subclinical infection. the development of highly sensitive rapid assays to screen for prion infection in blood is of high priority in order to facilitate the prevention of transmission via blood and blood products. in the present stud ... | 2009 | 19740979 |
| two adjacent nuclear factor-binding domains activate expression from the human prnp promoter. | the transmissible spongiform encephalopathies (tses) comprise a group of fatal degenerative neurological diseases in humans and other mammals. after infection, the cellular prion protein isoform prpc is converted to the pathological prpsc scrapie isoform. the continued conversion of prpc to prpsc requires de novo endogenous prp synthesis for disease progression. the human prion protein gene (prnp) promoter was therefore investigated to identify regulatory elements that could serve as targets for ... | 2009 | 19740434 |
| classical sheep scrapie in great britain: spatial analysis and identification of environmental and farm-related risk factors. | previous studies suggest that the spatial distribution of classical sheep scrapie in great britain is uneven and that certain flock characteristics may be associated with occurrence of the disease. however, the existence of areas of high and low disease-risk may also result from differences in the spatial distribution of environmental characteristics. in this study we explored the spatial pattern of classical scrapie in great britain between 2002 and 2005 and investigated the association between ... | 2009 | 19737376 |
| co-existence of scrapie prion protein types 1 and 2 in sporadic creutzfeldt-jakob disease: its effect on the phenotype and prion-type characteristics. | five phenotypically distinct subtypes have been identified in sporadic creutzfeldt-jakob disease (scjd), based on the methionine/valine polymorphic genotype of codon 129 of the prion protein (prp) gene and the presence of either one of the two protease k-resistant scrapie prion protein (prp(sc)) types identified as 1 and 2. the infrequent co-existence of both prp(sc) types in the same case has been known for a long time. recently, it has been reported, using type-specific antibodies, that the pr ... | 2009 | 19734292 |
| prion protein polymorphisms and estimation of risk of scrapie in east asian sheep. | allele and genotype frequency distributions of prion protein (prp) polymorphisms at three codons, 136, 154, and 171, in east asian sheep were determined by pcr-rflp analysis using 553 animals from nine local breeds of the northern group and four local breeds of the southern group. based on the genotype distribution, the risk score for scrapie was estimated. among the local breeds, arq appeared predominantly (0.7701-1), followed by arh and arr. from such a biased allele distribution, it was diffi ... | 2010 | 19731007 |
| establishment of bovine prion peptide-based monoclonal antibodies for identifying bovine prion. | to obtain high titer monoclonal antibodies (mcabs) which can react with mammalian prion protein (prp), balb/c mice were immunized with bovine (bo) prp peptide (boprp 209-228 aa) coupled to keyhole limpet hemocyanin (klh). the hybridoma cell lines secreting monoclonal antibodies against the peptide were established by cell fusion and cloning. the obtained mcabs were applied to detect recombinant human, bovine and hamster prp, cellular prion protein (prp(c)) in normal bovine brain and pathogenic s ... | 2009 | 19727594 |
| prp expression, prpsc accumulation and innervation of splenic compartments in sheep experimentally infected with scrapie. | in prion disease, the peripheral expression of prp(c) is necessary for the transfer of infectivity to the central nervous system. the spleen is involved in neuroinvasion and neural dissemination in prion diseases but the nature of this involvement is not known. the present study undertook the investigation of the spatial relationship between sites of prp(sc) accumulation, localisation of nerve fibres and prp(c) expression in the tissue compartments of the spleen of scrapie-inoculated and control ... | 2009 | 19727393 |
| diagnosis of the first cases of scrapie in poland. | this is the first report of cases of scrapie in poland. the disease was an atypical phenotype, diagnosed in two aged sheep which were found dead. brainstem samples from both animals were positive on the applied elisa rapid test, while the confirmatory immunoblot indicated abnormal banding patterns of protease resistant prion protein (prp(res)). the genotypes of these sheep were alrq/alhq and alrq/alrr. the absence of premonitory clinical signs, the advanced age of the affected sheep, the higher ... | 2010 | 19716323 |
| upregulation of mirna hsa-mir-342-3p in experimental and idiopathic prion disease. | abstract: the aim of our study was to analyze the differential expression of mirnas in the brains of bse-infected cynomolgus macaques as a model for creutzfeldt-jakob disease (cjd). micrornas (mirnas) are small noncoding rnas regulating gene expression by mrna targeting. among other functions they contribute to neuronal development and survival. recently, the lack of mirna processing has been shown to promote neurodegeneration and deregulation of several mirnas has been reported to be associated ... | 2009 | 19712440 |
| analysis of protein levels of 24 cytokines in scrapie agent-infected brain and glial cell cultures from mice differing in prion protein expression levels. | activation of microglia and astroglia is seen in many neurodegenerative diseases including prion diseases. activated glial cells produce cytokines as a protective response against certain pathogens and as part of the host inflammatory response to brain damage. in addition, cytokines might also exacerbate tissue damage initiated by other processes. in the present work using multiplex assays to analyze protein levels of 24 cytokines in scrapie agent-infected c57bl/10 mouse brains, we observed elev ... | 2009 | 19710140 |
| the evaluation of bias in scrapie surveillance: a review. | evaluation of surveillance systems is a common practice in the context of human health, but only recently has been applied in the veterinary field. commonly, a series of attributes are monitored to assess the system. suboptimal performance of the surveillance in relation to any of these attributes may lead to bias in the surveillance results. the intensity of scrapie surveillance has increased considerably in recent years as a result of public health concerns. in this paper, a number of approach ... | 2010 | 19709907 |
| influence of prion strain on prion protein adsorption to soil in a competitive matrix. | it is likely that the soil environment serves as a stable reservoir of infectious chronic wasting disease (cwd) and scrapie prions, as well as a potential reservoir of bovine spongiform encephalopathy (bse, or "mad cow" disease). prion adsorption to soil may play an important role in prion mobility, proteolysis, and infectivity. differences in prp environmental fate are possible due to the strain- and species-dependent structure of prp(sc). kinetic and isothermal studies of prp adsorption to san ... | 2009 | 19708348 |
| scrapie genetics before the discovery of prions. | 2010 | 19707236 | |
| p.asn176lys and p.met137thr dimorphisms of the prnp gene significantly decrease the susceptibility to classical scrapie in arq/arq sheep. | in this study, we investigated the susceptibility to scrapie of sarda breed sheep carrying the genotype arq/arq with additional polymorphisms at the prnp gene. to do this, we examined 256 scrapie-affected sheep and 320 flock-mate negative controls from 24 flocks. logistic regression analysis demonstrated that sheep carrying the arq/arq genotype with additional dimorphisms had lower risk of becoming scrapie affected when compared with those with arq/arq(wildtype) genotype. arq/arq genotypes that ... | 2009 | 19706028 |
| quantitative reverse-transcription polymerase chain reaction analysis of alzheimer's-associated genes in mouse scrapie. | prion and alzheimer's diseases are two apparently distinct disorders; however, the two proteinaceous species implicated in disease progression share a number of common features. in prion diseases a beta-rich conformer of the prion protein is the key molecule in the pathogenesis of prion disease, whereas in alzheimer's disease neurotoxicity is associated with the amyloid-beta peptide. these two molecules share common structural features and post-translational processing events and both undergo st ... | 2009 | 19697242 |
| high prevalence of scrapie in a dairy goat herd: tissue distribution of disease-associated prp and effect of prnp genotype and age. | following a severe outbreak of clinical scrapie in 2006-2007, a large dairy goat herd was culled and 200 animals were selected for post-mortem examinations in order to ascertain the prevalence of infection, the effect of age, breed and prnp genotype on the susceptibility to scrapie, the tissue distribution of diseaseassociated prp (prp(d)), and the comparative efficiency of different diagnostic methods. as determined by immunohistochemical (ihc) examinations with bar224 prp antibody, the prevale ... | 2009 | 19686637 |
| st1859 reduces prion infectivity and increase survival in experimental scrapie. | on the basis of the structural homologies between st1859 (1[(2-hydroxy-1-naphtyl)methyl]-2-naphthol) and the anti-prion agents and its anti-amyloidogenic activity, we tested whether this molecule altered the biochemical properties of aggregates formed in vitro by synthetic prion peptides and affected prion infectivity in experimental scrapie. co-incubation of st1859 with the peptides prp 106-126 and prp 82-146 reduced their fibrillogenic capacity and their resistance to digestion with protease k ... | 2009 | 19685199 |
| the impact of sheep breed on the risk of classical scrapie. | the risk of classical scrapie in sheep is associated with polymorphisms in the prion protein (prp) gene. in recent years, large-scale selective breeding programmes for sheep at lower risk of disease have been undertaken across the european union. we analysed large-scale datasets on scrapie and sheep demography to investigate additional effects of sheep breed on scrapie risk. there was evidence for variation between certain breeds in the scrapie risk of some prp genotypes, which could be caused b ... | 2010 | 19678970 |
| altered electroretinogram b-wave in a suffolk sheep experimentally infected with scrapie. | 2009 | 19666917 | |
| journal club. a systems biologist ponders how disparate ideas can sometimes come together beautifully. | 2009 | 19661875 | |
| prion metal interaction: is prion pathogenesis a cause or a consequence of metal imbalance? | functional role of cellular prion protein (prpc) has been hypothesized to be in metal homeostasis and providing cells with a superoxide dismutase (sod)-like activity to escape damage by reactive oxygen species (ros). prpc interacts with a range of divalent metal ions and undergoes cu2+ as well as zn2+-associated endocytosis, thereby maintaining homeostasis of these and other metal ions. conformational change to a beta-sheet rich, protease resistant entity, reminiscent of the disease-associated s ... | 2009 | 19660443 |
| interplay between 20s proteasomes and prion proteins in scrapie disease. | scrapie is a transmissible spongiform encephalopathy affecting the central nervous system in sheep. the key event in such neurodegeneration is the conversion of the normal prion protein (prp(c)) into the pathological isoform (prp(sc)). misfolded prion proteins are normally degraded by the proteasome. this work, analyzing models of scrapie disease, describes the in vivo relationship between the proteasome and prions. we report that the disease is associated with an increase of proteasome function ... | 2010 | 19658198 |
| frequent missense and insertion/deletion polymorphisms in the ovine shadoo gene parallel species-specific variation in prp. | the cellular prion protein prp(c) is encoded by the prnp gene. this protein is expressed in the central nervous system (cns) and serves as a precursor to the misfolded prp(sc) isoform in prion diseases. the prototype prion disease is scrapie in sheep, and whereas prnp exhibits common missense polymorphisms for v136a, r154h and q171r in ovine populations, genetic variation in mouse prnp is limited. recently the cns glycoprotein shadoo (sho) has been shown to resemble prp(c) both in a central hydr ... | 2009 | 19657386 |
| the unfolding of the prion protein sheds light on the mechanisms of prion susceptibility and species barrier. | prion diseases are a group of fatal neurodegenerative disorders that manifest as infectious, sporadic, or familial and are all associated with the misfolding of the prion protein (prp). disease-modulating polymorphisms in the prp amino acid sequence can make an individual more or less susceptible to infection. one example is the presence of arginine in place of glutamine at position 171 in sheep, which confers resistance to scrapie. to investigate whether the physical folding properties of prp a ... | 2009 | 19655812 |
| bovine macrophage degradation of scrapie and bse prpsc. | transmissible spongiform encephalopathies (tses), such as bovine spongiform encephalopathy (bse) and scrapie, display long incubation periods before prp(sc) accumulates in the central neuronal system (cns). the precise role that phagocytic cells, such as macrophages, play in prion pathogenesis is uncertain. in this study, the involvement of bovine macrophages at the early stage of prion infection was studied. brain homogenates of mouse scrapie and bse were degraded sequentially in the bovine mac ... | 2010 | 19647878 |
| proteomic profiling of prp27-30-enriched preparations extracted from the brain of hamsters with experimental scrapie. | transmissible spongiform encephalopathies (tses) are neurodegenerative disorders characterized by the accumulation in the cns of a pathological conformer (prp(tse)) of the host-encoded cellular prion protein (prp(c)). prp(tse) has a central role in the pathogenesis of the disease but other factors are likely involved in the pathological process. in this work we employed a multi-step proteomic approach for the identification of proteins that co-purify with the protease-resistant core of prp(tse) ... | 2009 | 19637240 |
| evaluation of the possible transmission of bse and scrapie to gilthead sea bream (sparus aurata). | in transmissible spongiform encephalopathies (tses), a group of fatal neurodegenerative disorders affecting many species, the key event in disease pathogenesis is the accumulation of an abnormal conformational isoform (prp(sc)) of the host-encoded cellular prion protein (prp(c)). while the precise mechanism of the prp(c) to prp(sc) conversion is not understood, it is clear that host prp(c) expression is a prerequisite for effective infectious prion propagation. although there have been many stud ... | 2009 | 19636413 |
| discrepant epidemiological patterns between classical and atypical scrapie in sheep flocks under french tse control measures. | the occurrence of secondary cases of atypical and classical scrapie was examined in 340 outbreaks of atypical and 296 of classical sheep scrapie detected in france during active surveillance programmes between 2002 and 2007. the prevalence of atypical scrapie in these flocks was 0.05% under selective culling and 0.07% under intensified monitoring i.e. not significantly different from that detected during active surveillance of the general population (p>0.5), whereas these figures were much highe ... | 2010 | 19635675 |
| role of copper and manganese in prion disease progression. | the cellular prion protein (prp(c)), a copper binding protein has a primary role in the pathogenesis of in prion diseases. in these diseases alterations in the levels of copper and manganese have been described but how these alterations are involved in the pathogenesis is still unknown. here we analysed synaptosomes of scrapie infected mice and observed a significant reduction in the amount of copper and an increase of the manganese content at day 100 after infection. moreover a reduction of the ... | 2009 | 19635464 |
| [alternations of tau protein and its phosphorylated profiles in the experimental hamsters infected by scrapie agents 263k and 139a]. | in human prion diseases, phosphorylated-tau deposition has been described in a rare genetic form, gerstmann-straussler-scheinker disease, but is not considered part of the neuropathological picture of creutzfeldt-jakob disease. to investigate the possible changes of tau and phosphorylated tau (ser396/ser404) in transmissible spongiform encephalopathies (tses), the expressions and transcriptions of above biological factors in the brain tissues of 263k- and 139a-infected hamsters were evaluated by ... | 2009 | 19634763 |
| the kuru infectious agent is a unique geographic isolate distinct from creutzfeldt-jakob disease and scrapie agents. | human sporadic creutzfeldt-jakob disease (scjd), endemic sheep scrapie, and epidemic bovine spongiform encephalopathy (bse) are caused by a related group of infectious agents. the new u.k. bse agent spread to many species, including humans, and clarifying the origin, specificity, virulence, and diversity of these agents is critical, particularly because infected humans do not develop disease for many years. as with viruses, transmissible spongiform encephalopathy (tse) agents can adapt to new sp ... | 2009 | 19633190 |
| influence of adam10 on prion protein processing and scrapie infectiosity in vivo. | both the cellular prion protein (prp(c)) and the amyloid precursor protein (app) are physiologically subjected to complex proteolytic processing events. while for app the proteinases involved--alpha-, beta- and gamma-secretase--have been identified in vitro and in vivo, the cleavage of prp(c) by now has been linked only to the shedding activity of the metalloproteinase adam10 and/or adam17 in cell culture. here we show that neuronal overexpression of the alpha-secretase adam10 in mice reduces al ... | 2009 | 19632330 |
| antiprion action of new cyclodextrin analogues. | prion disorders are characterised by the accumulation of a misfolded isoform (prpsc) of the host encoded prion protein (prpc). this paper examines the antiprion potential of cyclodextrin (cd) analogues and it identifies sulphated-beta-cyclodextrin, with a half-maximal inhibitory concentration (ic50) of 2.4 microm, as having 31-fold greater antiprion activity than that previously reported for beta-cyclodextrin (betacd). | 2009 | 19631725 |
| differential display detects host nucleic acid motifs altered in scrapie-infected brain. | the transmissible spongiform encephalopathies (tses) including scrapie have been attributed to an infectious protein or prion. infectivity is allied to conversion of the endogenous nucleic-acid-binding protein prp to an infectious modified form known as prp(sc). the protein-only theory does not easily explain the enigmatic properties of the agent including strain variation. it was previously suggested that a short nucleic acid, perhaps host-encoded, might contribute to the pathoetiology of the t ... | 2009 | 19631225 |
| quantifying diversity losses due to selection for scrapie resistance in three endangered spanish sheep breeds using microsatellite information. | the effect of selection for scrapie resistance on genetic variability in three endangered spanish sheep breeds (colmenareña, mallorquina and rubia de el molar) was studied using two different criteria for quantifying contributions to genetic variability: (a) molecular coancestry or genetic identity; and (b) average number of alleles per locus or allelic richness. a total of 236 (81 colmenareña, 76 mallorquina and 79 rubia de el molar) individuals were genotyped for the prp gene and for 22 micros ... | 2009 | 19625092 |
| pathological phenotype of sheep scrapie after blood transfusion. | blood transfusion practices have resulted in iatrogenic cases of variant creutzfeldt-jakob disease (vcjd) and it is known that sheep blood is also infectious in the pre-clinical stages of natural scrapie and experimentally induced bovine spongiform encephalopathy (bse). further investigations have also shown that the pathological phenotype of sheep bse and human vcjd is maintained after blood transfusion. the present study describes the pathological phenotype, in terms of accumulation of the dis ... | 2010 | 19625026 |
| therapeutic interventions ameliorating prion disease. | of the many unresolved issues in relation to prion diseases, effective treatments remain an elusive exigency, although some progress has been made. this review describes disease-ameliorating therapeutic strategies reported to date in animal models of prion disease, as well as providing a brief overview of selected completed human treatment trials. included in vivo studies have been broadly dichotomized according to the time of introduction of the treatment in relation to animal inoculation and a ... | 2009 | 19622059 |
| [analysis of monoclonal antibody binding sites in ovine prion protein]. | binding sites of five monoclonal antibodies were obtained by reinforceable method of overlapping recombinant prion protein and synthetic peptide. overlapping peptides of prp core were expressed in escherichia coli by insertion of serial pcr amplicons of ovine prp gene fragments into pet32a. the expressed fusion peptides were then tested for the binding activity to prp monoclonal antibodies in western blotting. the binding sites of 5 monoclonal antibodies of ovine prp were located respectively as ... | 2009 | 19621573 |
| establishment of a stable prp(sc) panel from brain tissues of experimental hamsters with scrapie strain 263k. | to establish a stable prp(sc) panel from brain tissues of experimental hamsters infected with scrapie agent 263k for evaluating diagnostic techniques of human and animals' prion diseases. | 2009 | 19618693 |
| reflections on a half-century in the field of transmissible spongiform encephalopathy. | the subject of transmissible spongiform encephalopathy may properly be said to have begun with the experimental transmission of scrapie by cuillé and chelle in 1936, although creutzfeldt and jakob had described the disease that bears their names in 1920-21. thirty more years passed before the human disease was also shown to be transmissible, in 1966, and the following half century has seen the field move from classical biology to molecular biology and genetics, and from 'slow virus' to host-enco ... | 2009 | 19618333 |
| peptide nmhrypnq of the cellular prion protein (prp(c)) inhibits aggregation and is a potential key for understanding prion-prion interactions. | pathogenesis of transmissible spongiform encephalopathies is correlated with a conversion of the normal cellular form of the prion protein (prp(c)) into the abnormal isoform (scrapie form of prp). contact of the normal prp with its abnormal isoform, the scrapie form of prp, induces the transformation. knowledge of molecules that inhibit such contacts leads to an understanding of the mechanism of the aggregation, and these molecules may serve as leads for drugs against transmissible spongiform en ... | 2009 | 19607841 |
| spatial distribution of the active surveillance of sheep scrapie in great britain: an exploratory analysis. | this paper explores the spatial distribution of sampling within the active surveillance of sheep scrapie in great britain. we investigated the geographic distribution of the birth holdings of sheep sampled for scrapie during 2002 - 2005, including samples taken in abattoir surveys (c. 83,100) and from sheep that died in the field ("fallen stock", c. 14,600). we mapped the birth holdings by county and calculated the sampling rate, defined as the proportion of the holdings in each county sampled b ... | 2009 | 19607705 |
| reduction of prion infectivity and levels of scrapie prion protein by lithium aluminum hydride: implications for rna in prion diseases. | previous studies indicate that rna may be required for proteinase-resistant prion protein (prp) amplification and for infectious prion formation in vitro, suggesting that rna molecules may function as cellular cofactors for abnormal prp (prpsc) formation and become part of the structure of the infectious agent. to address this question, we used chemicals that can cleave phosphodiester bonds of rna and assessed their effects on the infectious agent. lithium aluminum hydride, a reducing agent that ... | 2009 | 19606066 |
| characterization of a us sheep scrapie isolate with short incubation time. | scrapie is a naturally occurring fatal neurodegenerative disease of sheep and goats. susceptibility to the disease is partly dependent upon the genetic makeup of the host. in a previous study it was shown that sheep intracerebrally inoculated with us scrapie inoculum (no. 13-7) developed terminal disease within an average of 19 months. we have since produced an inoculum, no. x124 from pooled brains of us-origin sheep scrapie, that results in incubations nearly threefold shorter. the present stud ... | 2009 | 19605918 |
| failure to transmit scrapie infection by transferring preimplantation embryos from naturally infected donor sheep. | the objective of the study was to examine whether or not the preimplantation embryo can act as a carrier of classic scrapie infection. the study was carried out on quarantined premises with sheep of highly susceptible scrapie genotypes. uninfected embryos, collected from new zealand-derived suffolk ewes, were surgically transferred into recipient ewes that were also of new zealand origin. seventeen negative control lambs were born on the study premises from these embryo transfers. thirty-nine ex ... | 2009 | 19604572 |
| doxorubicin and congo red effectiveness on prion infectivity in golden syrian hamster. | the effect of doxorubicin and congo red on prion protein (prp) infectivity in experimental scrapie was studied to better understand the effect of these compounds in prion diseases and to establish whether a dose-response correlation exists for congo red. this was performed in order to test the effectiveness of compounds that may easily be used in human prion diseases. brain homogenate containing membrane bound prpsc monomers was used as inoculum and was previously incubated with doxorubicin 10(- ... | 2009 | 19596920 |
| distinct structures of scrapie prion protein (prpsc)-seeded versus spontaneous recombinant prion protein fibrils revealed by hydrogen/deuterium exchange. | the detailed structures of prion disease-associated, partially protease-resistant forms of prion protein (e.g. prp(sc)) are largely unknown. prp(sc) appears to propagate itself by autocatalyzing the conformational conversion and oligomerization of normal prion protein (prp(c)). one manifestation of prp(sc) templating activity is its ability, in protein misfolding cyclic amplification reactions, to seed the conversion of recombinant prion protein (rprp) into aggregates that more closely resemble ... | 2009 | 19596861 |
| prion protein detection via direct immuno-quantitative real-time pcr. | we describe a simple and robust assay for the quantitative detection of prions using immuno-quantitative real-time pcr (iq-rt-pcr) made possible by a direct conjugate of a prion-specific antibody (icsm35) and a synthetic 99-bp dna tail. the dna tail was engineered to include a single scrfi restriction site, which enabled subsequent quantification of restricted dna tails using real-time pcr. the assay was tested with scrapie prions bound to polyvinylidene difluoride membranes and to 96-well plate ... | 2009 | 19596031 |
| phosphorylation of prion protein at serine 43 induces prion protein conformational change. | the cause of the conformational change of normal cellular prion protein (prp) into its disease-associated form is unknown. posttranslational modifications, such as glycosylation, acetylation, s-nitrosylation, and phosphorylation, are known to induce protein conformational changes. here, we investigated whether phosphorylation could induce the conformational change of prp because prp contains several kinase motifs and has been found recently in the cytosol, in which kinases generally reside. neur ... | 2009 | 19587281 |
| sequence analysis of the prion protein gene in mongolian gazelles (procapra gutturosa). | prion diseases are a group of human and animal neurodegenerative conditions, which are caused by the deposition of an abnormal isoform prion protein (prpsc) encoded by a single copy prion protein gene (prnp). in sheep, genetic variations of prnp were found to be associated with the incubation period, susceptibility, and species barrier to the scrapie disease. we investigated the sequence and polymorphisms of the prion protein gene of mongolian gazelles (gprnp). gprnp gene sequence analysis of bl ... | 2009 | 19579063 |
| evaluating different prp genotype selection strategies for expected severity of scrapie outbreaks and genetic progress in performance in commercial sheep. | stochastic computer simulations were used for quantifying the effect of selecting on prion protein (prp) genotype on the risk of major outbreaks of classical scrapie and the rate of genetic progress in performance in commercial sheep populations already undergoing selection on performance. the risk of a major outbreak on a flock was measured by the basic reproduction ratio (r(0)). the effectiveness of different prp selection strategies for reducing the population risk was assessed by the percent ... | 2009 | 19577317 |
| human variant creutzfeldt-jakob disease and sheep scrapie prp(res) detection using seeded conversion of recombinant prion protein. | the pathological isoform of the prion protein (prp(res)) can serve as a marker for prion diseases, but more practical tests are needed for preclinical diagnosis and sensitive detection of many prion infections. previously we showed that the quaking-induced conversion (quic) assay can detect sub-femtogram levels of prp(res) in scrapie-infected hamster brain tissue and distinguish cerebral spinal fluid (csf) samples from normal and scrapie-infected hamsters. we now report the adaptation of the qui ... | 2009 | 19570812 |
| prion protein (prp) knock-out mice show altered iron metabolism: a functional role for prp in iron uptake and transport. | despite overwhelming evidence implicating the prion protein (prp) in prion disease pathogenesis, the normal function of this cell surface glycoprotein remains unclear. in previous reports we demonstrated that prp mediates cellular iron uptake and transport, and aggregation of prp to the disease causing prp-scrapie (prp(sc)) form results in imbalance of iron homeostasis in prion disease affected human and animal brains. here, we show that selective deletion of prp in transgenic mice (prp(ko)) alt ... | 2009 | 19568430 |
| nor98 scrapie identified in the united states. | a distinct strain of scrapie identified in sheep of norway in 1998 has since been identified in numerous countries throughout europe. the disease is known as nor98 or nor98-like scrapie, among other names. distinctions between classic scrapie and nor98 scrapie are made based on histopathology and immunodiagnostic results. there are also differences in the epidemiology, typical signalment, and likelihood of clinical signs being observed. in addition, sheep that have genotypes associated with resi ... | 2009 | 19564493 |
| role of adams in the ectodomain shedding and conformational conversion of the prion protein. | the cellular prion protein (prp(c)) is essential for the pathogenesis and transmission of prion diseases. prp(c) is bound to the plasma membrane via a glycosylphosphatidylinositol anchor, although a secreted, soluble form has also been identified. previously we reported that prp(c) is subject to ectodomain shedding from the membrane by zinc metalloproteinases with a similar inhibition profile to those involved in shedding the amyloid precursor protein. here we have used gain-of-function (overexp ... | 2009 | 19564338 |
| elimination capacity of a tse-model agent in the manufacturing process of alphanate/fanhdi, a human factor viii/vwf complex concentrate. | the variant creutzfeldt-jakob disease (vcjd) is a transmissible spongiform encephalopathy (tse), mainly present in the uk and is associated with the ingestion of bovine products affected with bovine spongiform encephalopathy. manufacturers of biological products must investigate the ability of their production processes to remove tse agents. we studied the purification steps in the manufacturing process of two fviii/vwf concentrates (alphanate) and fanhdi in their ability to eliminate an experim ... | 2009 | 19563480 |
| design and validation of a high-throughput assay to detect codon 146 polymorphisms in the caprine prion protein gene. | in sheep, scrapie susceptibility is so strongly associated with single nucleotide polymorphisms (snps) in the gene encoding the prion protein (prp) that this linkage constitutes the basis for selective breeding strategies directed toward controlling the disease. for goats, in contrast, the association between scrapie susceptibility/resistance and variations in the prp gene is far weaker, with only a few identified snps showing an influence on scrapie susceptibility. a recent survey of prp genoty ... | 2009 | 19559665 |
| the cellular prion protein and its role in alzheimer disease. | the cellular prion protein (prp(c)) is a membrane-bound glycoprotein especially abundant in the central nervous system (cns). the scrapie prion protein (prp(sc,) also termed prions) is responsible of transmissible spongiform encephalopathies (tse), a group of neurodegenerative diseases which affect humans and other mammal species, although the presence of prp(c) is needed for the establishment and further evolution of prions. the present work compares the expression and localization of prp(c) be ... | 2009 | 19556894 |
| prion removal effect of a specific affinity ligand introduced into the manufacturing process of the pharmaceutical quality solvent/detergent (s/d)-treated plasma octaplaslg. | a new chromatographic step for the selective binding of abnormal prion protein (prp(sc)) was developed, and optimization for prp(sc) capture was achieved by binding to an affinity ligand attached to synthetic resin particles. this step was implemented into the manufacturing process of the solvent/detergent (s/d)-treated biopharmaceutical quality plasma octaplas to further improve the safety margin in terms of risk for variant creutzfeldt-jakob disease (vcjd) transmission. | 2009 | 19548963 |
| variable levels of 37-kda/67-kda laminin receptor (rpsa) mrna in ovine tissues: potential contribution to the regulatory processes of prpsc propagation? | the 37-kda laminin receptor precursor/67-kda laminin receptor (lrp/lr, also known as ribosomal protein sa, rpsa) has been reported to be involved in cancer development and prion internalization. previous studies have shown that the lrp/lr is expressed in a wide variety of tissues. in particular, expression of lrp/lr mrna may be closely related to the degree of prp(sc) propagation. this study presents a detailed investigation of the lrp/lr mrna expression levels in eleven normal ovine tissues. us ... | 2009 | 19544211 |
| comparative prion disease gene expression profiling using the prion disease mimetic, cuprizone. | identification of genes expressed in response to prion infection may elucidate biomarkers for disease, identify factors involved in agent replication, mechanisms of neuropathology and therapeutic targets. although several groups have sought to identify gene expression changes specific to prion disease, expression profiles rife with cell population changes have consistently been identified. cuprizone, a neurotoxicant, qualitatively mimics the cell population changes observed in prion disease, res ... | 2009 | 19535908 |
| genetic analysis of the sprn gene in ruminants reveals polymorphisms in the alanine-rich segment of shadoo protein. | prion diseases in ruminants, especially sheep scrapie, cannot be fully explained by prnp genetics, suggesting the influence of a second modulator gene. the sprn gene is a good candidate for this role. the sprn gene encodes the shadoo protein (sho) which has homology to the prnp gene encoding prion protein (prp). murine sho has a similar neuroprotective activity to prp and sprn gene variants are associated with human prion disease susceptibility. sprn gene sequences were obtained from 14 species ... | 2009 | 19515828 |
| immunohistochemical characterisation of classical scrapie neuropathology in sheep. | neuroinflammation elicited by prp(res) (resistant prion protein [prp]) deposits in the central nervous system (cns) has been shown to involve cellular and oxidative stress responses in bovine spongiform encephalopathy (bse) as well as in several murine models of transmissible spongiform encephalopathy (tse). additionally, deregulation of water homeostasis has been suggested to be a further component of the spongiform changes observed in tses. the aim of the present study was to characterize the ... | 2009 | 19515381 |
| shadoo (sprn) and prion disease incubation time in mice. | prion diseases are transmissible neurodegenerative disorders of mammalian species and include scrapie, bovine spongiform encephalopathy (bse), and variant creutzfeldt-jakob disease (vcjd). the prion protein (prp) plays a key role in the disease, with coding polymorphism in both human and mouse influencing disease susceptibility and incubation time, respectively. other genes are also thought to be important and a plausible candidate is sprn, which encodes the prp-like protein shadoo (sho). sho is ... | 2009 | 19513788 |
| state-of-the-art review of goat tse in the european union, with special emphasis on prnp genetics and epidemiology. | scrapie is a fatal, neurodegenerative disease of sheep and goats. it is also the earliest known member in the family of diseases classified as transmissible spongiform encephalopathies (tse) or prion diseases, which includes creutzfeldt-jakob disease in humans, bovine spongiform encephalopathy (bse), and chronic wasting disease in cervids. the recent revelation of naturally occurring bse in a goat has brought the issue of tse in goats to the attention of the public. in contrast to scrapie, bse p ... | 2009 | 19505422 |
| two unusual bovine spongiform encephalopathy cases detected in great britain. | bovine spongiform encephalopathy (bse) was first identified in great britain (gb) in 1986 and was subsequently detected in many other countries, worldwide. a decade after the start of the bovine epidemic, the first cases of new variant creutzfeldt-jakob disease (vcjd) in humans were linked to probable ingestion of bse infected tissue, highlighting a new zoonotic disease. an abnormal protease-resistant protein (prp(res)) in a diseased subject, derived from a post-translational change of a normal ... | 2009 | 19497088 |
| prions are secreted in milk from clinically normal scrapie-exposed sheep. | the potential spread of prion infectivity in secreta is a crucial concern for prion disease transmission. here, serial protein misfolding cyclic amplification (spmca) allowed the detection of prions in milk from clinically affected animals as well as scrapie-exposed sheep at least 20 months before clinical onset of disease, irrespective of the immunohistochemical detection of protease-resistant prp(sc) within lymphoreticular and central nervous system tissues. these data indicate the secretion o ... | 2009 | 19494004 |
| the effect of metal imbalances on scrapie neurodegeneration. | environmental exposure to metal appears to enhance susceptibility to transmissible spongiform encephalopathies (tses); however, published data are not conclusive. the current study focuses on assessing the effects of copper depletion and/or manganese enhancement in the diet on susceptibility to scrapie and this disease progression. the degree of spongiosis was the highest in the animals that received a copper- depleted diet. these observations suggest that this diet contributes to the scrapie le ... | 2010 | 19486493 |
| detection of classical and atypical/nor98 scrapie by the paraffin-embedded tissue blot method. | the paraffin-embedded tissue (pet) blot method was used to investigate sections of the central nervous system and lymphatic tissues from 24 cases of classical scrapie and 25 cases of atypical/nor98 scrapie in sheep and four healthy control sheep. the pet blot detected deposits of prp(sc) in the brain tissue of all 49 sheep with scrapie but no prp(sc) labelling could be detected in the control sheep. by contrast, not all the atypical/nor98 scrapie cases were detectable by immunohistochemistry. th ... | 2009 | 19483208 |
| abnormal prion protein is associated with changes of plasma membranes and endocytosis in bovine spongiform encephalopathy (bse)-affected cattle brains. | transmissible spongiform encephalopathies (tses) or prion diseases are fatal neurodegenerative diseases of man and animals characterized by vacuolation and gliosis of neuropil and the accumulation of abnormal isoforms of a host protein known as prion protein (prp). it is widely assumed that the abnormal isoforms of prp (prp(d), disease-specific form of prp) are the proximate cause of neurodegeneration. | 2009 | 19473293 |
| neuroinvasion in sheep transmissible spongiform encephalopathies: the role of the haematogenous route. | it is generally believed that after oral exposure to transmissible spongiform encephalopathy (tse) agents, neuroinvasion occurs via the enteric nervous system (ens) and the autonomic nervous system. as a result, the dorsal motor nucleus of the vagus nerve is the initial point of disease-associated prion protein (prp(d)) accumulation in the brain. hypothesis and aim: if direct ens invasion following oral infection results in an early and specific brain targeting for prp(d) accumulation, such topo ... | 2009 | 19473292 |
| [establishment of a prion disease prp(sc) panel from the brain tissues of experimental hamsters infected with scrapie agent 263k]. | to establish a prion disease prp(sc) panel from the brain tissues of experimental hamsters and to address the stability of the panel conserved under the specific condition, for evaluating the diagnostic techniques of human and animal's prion diseases. | 2008 | 19469162 |
| feasibility of infectious prion digestion using mild conditions and commercial subtilisin. | two serine protease enzymes, subtilisin 309 and subtilisin 309-v, were used to digest brain homogenates containing high levels of prion infectivity using mildly alkaline conditions to investigate prion decontamination methods. to establish that prp(res) infectivity was eliminated, we utilized the rocky mountain laboratory (rml) mouse-adapted scrapie model system for bioassay. only one digestion condition (subtilisin 309 at 138mau/ml, 55 degrees c and 14h digestion time ph 7.9) was considered to ... | 2009 | 19467265 |
| effects of clioquinol on memory impairment and the neurochemical modifications induced by scrapie infection in golden hamsters. | prion protein (prp) is a glycoprotein expressed on the surface of neurons and glial cells. its pathological isoform (prp(res)) is protease resistant, and involved in the pathogenesis of a number of transmissible encephalopathies (tses). one common feature of neurodegenerative diseases, including tses, is oxidative stress, which may be responsible not only for the dysfunction or death of neuronal cells, but also cognitive deficits. clioquinol (5-chloro-7-iodo-8-quinolinol) chelates zinc and coppe ... | 2009 | 19463795 |
| species and strain glycosylation patterns of prpsc. | a key event in transmissible spongiform encephalopathies (tses) is the conversion of the soluble, protease-sensitive glycosylated prion protein (prp(c)) to an abnormally structured, aggregated and partially protease-resistant isoform (prp(sc)). both prp isoforms bear two potential glycosylation sites and thus in a typical western blot with an anti-prp antibody three distinct bands appear, corresponding to the di-, mono- or unglycosylated forms of the protein. the relative intensity and electroph ... | 2009 | 19461968 |
| hyperefficient prp sc amplification of mouse-adapted bse and scrapie strain by protein misfolding cyclic amplification technique. | abnormal forms of prion protein (prp(sc)) accumulate via structural conversion of normal prp (prp(c)) in the progression of transmissible spongiform encephalopathy. under cell-free conditions, the process can be efficiently replicated using in vitro prp(sc) amplification methods, including protein misfolding cyclic amplification. these methods enable ultrasensitive detection of prp(sc); however, there remain difficulties in utilizing them in practice. for example, to date, several rounds of prot ... | 2009 | 19459939 |
| efficacy of phthalocyanine tetrasulfonate against mouse-adapted human prion strains. | in vitro and in vivo studies have shown that phthalocyanine tetrasulfonate (pcts), a cyclic tetrapyrrole compound, is an efficient antiscrapie drug. to investigate the spectrum of pcts against prion diseases, we tested the effect of pcts on two mouse-adapted human strains. we also tested pcts in rodents infected with two scrapie strains (139a and 263k). pcts treatment significantly prolonged mean survival times of all infected animals. these results show that pcts is effective on different prion ... | 2009 | 19458902 |
| frequency of genotypes in the prp prion protein gene locus in the polish sheep population. | scrapie is an invariably fatal transmissible neurodegenerative disease of sheep, goats and moufflons, characterised by ataxia, lower body weight and changes in behaviour. the aim of this study was to determine the genotype distribution at codons 136, 154 and 171 of the prp locus in sheep bred in poland. the genotypes of 801 sheep representing 10 different breeds and crossbreds were analysed using real-time pcr allele discrimination method. the combination of point mutations of the three codons ( ... | 2009 | 19457772 |
| interlaboratory trial on tse rapid tests for the control of the italian scrapie surveillance network. | scrapie, a neurodegenerative disease of sheep and goats and one of several transmissible spongiform encephalopathies (tses) has been subject to mandatory active surveillance in eu through rapid testing since 2002. regulation ec/999/2001 on tse surveillance requires that each member state's national reference laboratory for tse periodically verifies diagnostic standards and methods by comparative testing. in 2007 the italian reference centre carried out the first ring trial for classical scrapie ... | 2009 | 19457624 |
| surround optical fiber immunoassay (sofia): an ultra-sensitive assay for prion protein detection. | we describe the development of a new technology (sofia) and demonstrate its utility by establishing a sensitive and specific assay for prp(sc). sofia is a surround optical fiber immunoassay which is comprised of a set of specific monoclonal antibodies and comprehensive capture of high energy fluorescence emission. in its current format, this system is capable of detecting less than 10 attogram (ag) of hamster, sheep and deer recombinant prp. approximately 10 ag of prp(sc) from 263 k-infected ham ... | 2009 | 19442839 |
| prion disease development in slow wallerian degeneration (wld(s)) mice. | axon destruction represents one aspect of prion disease-associated neurodegeneration. we characterized here the scrapie infection of wld(s)-mice in comparison to wild-type c57bl/6 controls to determine whether mechanisms involved in wallerian degeneration contribute to disease development in this murine model system. the wld(s) mutation had neither an effect on survival times, nor on typical hallmarks of a prion infection like deposition of misfolded prp(sc) and glia activation. at the ultrastru ... | 2009 | 19429141 |
| identification of an intracellular site of prion conversion. | prion diseases are fatal, neurodegenerative disorders in humans and animals and are characterized by the accumulation of an abnormally folded isoform of the cellular prion protein (prp(c)), denoted prp(sc), which represents the major component of infectious scrapie prions. characterization of the mechanism of conversion of prp(c) into prp(sc) and identification of the intracellular site where it occurs are among the most important questions in prion biology. despite numerous efforts, both of the ... | 2009 | 19424437 |
| on the question of proportionality of the count of observed scrapie cases and the size of holding. | the present paper investigates the question of a suitable basic model for the number of scrapie cases in a holding and applications of this knowledge to the estimation of scrapie-affected holding population sizes and adequacy of control measures within holding. is the number of scrapie cases proportional to the size of the holding in which case it should be incorporated into the parameter of the error distribution for the scrapie counts? or, is there a different - potentially more complex - rela ... | 2009 | 19419538 |
| design of anti- and pro-aggregation variants to assess the effects of methionine oxidation in human prion protein. | prion disease is characterized by the alpha-->beta structural conversion of the cellular prion protein (prp(c)) into the misfolded and aggregated "scrapie" (prp(sc)) isoform. it has been speculated that methionine (met) oxidation in prp(c) may have a special role in this process, but has not been detailed and assigned individually to the 9 met residues of full-length, recombinant human prp(c) [rhprp(c)(23-231)]. to better understand this oxidative event in prp aggregation, the extent of periodat ... | 2009 | 19416900 |
| blood chimerism confounds genetic relative susceptibility testing for classical scrapie in sheep. | classical scrapie disease is a transmissible spongiform encephalopathy of sheep that is enzootic in the united states. susceptibility of sheep to classical scrapie is linked to single nucleotide polymorphisms in the prion protein gene (prnp), forming the basis for genetic testing strategies used by national efforts to eradicate scrapie. such efforts are occasionally hampered by inconclusive results stemming from the detection of "complex" genotypes. naturally occurring cases of ovine chimerism a ... | 2009 | 19407081 |
| comparison of strategies for substantiating freedom from scrapie in a sheep flock. | the public health threat represented by a potential circulation of bovine spongiform encephalopathy agent in sheep population has led european animal health authorities to launch large screening and genetic selection programmes. if demonstrated, such a circulation would have dramatic economic consequences for sheep breeding sector. in this context, it is important to evaluate the feasibility of qualification procedures that would allow sheep breeders demonstrating their flock is free from scrapi ... | 2009 | 19405956 |
| a case-control study on the origin of atypical scrapie in sheep, france. | a matched case-control study (95 cases and 220 controls) was designed to study risk factors for atypical scrapie in sheep in france. we analyzed contacts with animals from other flocks, lambing and feeding practices, and exposure to toxic substances. data on the prnp genotype were collected for some case and control animals and included in a complementary analysis. sheep dairy farms had a higher risk for scrapie (odds ratio [or] 15.1, 95% confidence interval [ci] 3.3-69.7). lower risk was associ ... | 2009 | 19402956 |
| distinct spatial activation of intrinsic and extrinsic apoptosis pathways in natural scrapie: association with prion-related lesions. | neurodegeneration and gliosis are the main neuropathological features of prion diseases. however, the molecular mechanisms involved in these processes remain unclear. several studies have demonstrated changes in the expression of apoptotic factors and inflammatory cytokines in animals with experimental infection. here we present the expression profiles of 15 genes implicated in the intrinsic and extrinsic apoptotic pathways in the central nervous systems of sheep naturally infected with scrapie. ... | 2009 | 19401142 |
| prnp haplotype distribution in moroccan goats. | susceptibility/resistance to scrapie in sheep and goats is influenced by host prion protein gene (prnp) genotype. in this study, we report the analysis of prion protein gene polymorphisms in 137 goats of two moroccan populations: d'man and chaouni. we found seven previously described amino acid polymorphisms at codons 37, 127, 137, 142, 154, 222 and 240, as well as three known silent mutations. in addition, we identified three new allelic variants: 101r and 139s in d'man goats and 145d in d'man ... | 2009 | 19397523 |
| prion protein nmr structure from tammar wallaby (macropus eugenii) shows that the beta2-alpha2 loop is modulated by long-range sequence effects. | nmr structures are presented for the recombinant construct of residues 121-230 from the tammar wallaby (macropus eugenii) prion protein (prp) twprp(121-230) and for the variant mouse prps mprp[y225a,y226a](121-231) and mprp[v166a](121-231) at 20 degrees c and ph 4.5. all three proteins exhibit the same global architecture as seen in other recombinant prp(c)s (cellular isoforms of prp) and shown to prevail in natural bovine prp(c). special interest was focused on a loop that connects the beta2-st ... | 2009 | 19393664 |
| pathologic prion protein infects cells by lipid-raft dependent macropinocytosis. | transmissible spongiform encephalopathies, including variant-creutzfeldt-jakob disease (vcjd) in humans and bovine spongiform encephalopathies in cattle, are fatal neurodegenerative disorders characterized by protein misfolding of the host cellular prion protein (prp(c)) to the infectious scrapie form (prp(sc)). however, the mechanism that exogenous prp(sc) infects cells and where pathologic conversion of prp(c) to the prp(sc) form occurs remains uncertain. here we report that similar to the mec ... | 2008 | 19390657 |
| glycosylation-related gene expression profiling in the brain and spleen of scrapie-affected mouse. | a central event in the formation of infectious prions is the conformational change of a host-encoded glycoprotein, prp(c), into a pathogenic isoform, prp(sc). the molecular requirements for efficient prp conversion remain unknown. altered glycosylation has been linked to various pathologies and the n-glycans harbored by two prion protein isoforms are different. in order to search for glycosylation-related genes that could mark prion infection, we used a glycosylation-dedicated microarray that al ... | 2009 | 19386898 |
| anti-prp mab 6d11 suppresses prp(sc) replication in prion infected myeloid precursor line fdc-p1/22l and in the lymphoreticular system in vivo. | the pathogenesis of prion diseases is related to conformational transformation of cellular prion protein (prp(c)) into a toxic, infectious, and self-replicating conformer termed prp(sc). following extracerebral inoculation, the replication of prp(sc) is confined for months to years to the lymporeticular system (lrs) before the secondary cns involvement results in occurrence of neurological symptoms. therefore, replication of prp(sc), in the early stage of infection can be targeted by therapeutic ... | 2009 | 19385058 |