Publications
| Title | Abstract | Year Filter | PMID(sorted descending) Filter |
|---|
| molecular typing of protease-resistant prion protein in transmissible spongiform encephalopathies of small ruminants, france, 2002-2009. | the agent that causes bovine spongiform encephalopathy (bse) may be infecting small ruminants, which could have serious implications for human health. to distinguish bse from scrapie and to examine the molecular characteristics of the protease-resistant prion protein (prp(res)), we used a specifically designed western blot method to test isolates from 648 sheep and 53 goats. during 2002-2009, classical non-nor98 transmissible spongiform encephalopathy had been confirmed among ≈1.7 million small ... | 2011 | 21192855 |
| isolation of proteinase k-sensitive prions using pronase e and phosphotungstic acid. | disease-related prion protein, prp(sc), is classically distinguished from its normal cellular precursor, prp(c), by its detergent insolubility and partial resistance to proteolysis. molecular diagnosis of prion disease typically relies upon detection of protease-resistant fragments of prp(sc) using proteinase k, however it is now apparent that the majority of disease-related prp and indeed prion infectivity may be destroyed by this treatment. here we report that digestion of rml prion-infected m ... | 2010 | 21187933 |
| [interaction between various 14-3-3beta segments and prp in vitro]. | objective to study the potential interaction between prp protein. | 2010 | 21186515 |
| nuclease resistant circular dnas copurify with infectivity in scrapie and cjd. | in transmissible encephalopathies (tses), it is commonly believed that the host prion protein transforms itself into an infectious form that encodes the many distinct tse agent strains without any nucleic acid. using a ф29 polymerase and chromatography strategy, highly infectious culture and brain preparations of three different geographic tse agents all contained novel circular dnas. two circular "sphinx" sequences, of 1.8 and 2.4 kb, copurified with infectious particles in sucrose gradients an ... | 2010 | 21165784 |
| effect of fixation on brain and lymphoreticular vcjd prions and bioassay of key positive specimens from a retrospective vcjd prevalence study. | anonymous screening of lymphoreticular tissues removed during routine surgery has been applied to estimate the uk population prevalence of asymptomatic vcjd prion infection. the retrospective study of hilton et al(j pathol 2004; 203: 733-739) found accumulation of abnormal prion protein in three formalin-fixed appendix specimens. this led to an estimated uk prevalence of vcjd infection of ∼1 in 4000, which remains the key evidence supporting current risk reduction measures to reduce iatrogenic t ... | 2010 | 21154694 |
| structure-activity relationship refinement and further assessment of indole-3-glyoxylamides as a lead series against prion disease. | structure-activity relationships within the indole-3-glyoxylamide series of antiprion agents have been explored further, resulting in discovery of several new compounds demonstrating excellent activity in a cell line model of prion disease (ec₅₀ <10 nm). after examining a range of substituents at the para-position of the n-phenylglyoxylamide moiety, five-membered heterocycles containing at least two heteroatoms were found to be optimal for the antiprion effect. a number of modifications were mad ... | 2011 | 21154498 |
| rapid end-point quantitation of prion seeding activity with sensitivity comparable to bioassays. | a major problem for the effective diagnosis and management of prion diseases is the lack of rapid high-throughput assays to measure low levels of prions. such measurements have typically required prolonged bioassays in animals. highly sensitive, but generally non-quantitative, prion detection methods have been developed based on prions' ability to seed the conversion of normally soluble protease-sensitive forms of prion protein to protease-resistant and/or amyloid fibrillar forms. here we descri ... | 2010 | 21152012 |
| molecular interactions between prions as seeds and recombinant prion proteins as substrates resemble the biological interspecies barrier in vitro. | prion diseases like creutzfeldt-jakob disease in humans, scrapie in sheep or bovine spongiform encephalopathy are fatal neurodegenerative diseases, which can be of sporadic, genetic, or infectious origin. prion diseases are transmissible between different species, however, with a variable species barrier. the key event of prion amplification is the conversion of the cellular isoform of the prion protein (prp(c)) into the pathogenic isoform (prp(sc)). we developed a sodiumdodecylsulfate-based prp ... | 2010 | 21151607 |
| alimentary prion infections: touchdown in the intestine. | neurodegenerative diseases are caused by proteinaceous aggregates, usually consisting of misfolded proteins which are often typified by a high proportion of β-sheets, which accumulate in the central nervous system. these diseases, including morbus alzheimer, parkinson disease and transmissible spongiform encephalopathies (tses)--also termed prion disorders--afflict a substantial proportion of the human population and as such the etiology and pathogenesis of these diseases has been the focus of m ... | 2011 | 21150306 |
| heparin binding by murine recombinant prion protein leads to transient aggregation and formation of rna-resistant species. | the conversion of cellular prion protein (prp(c)) into the pathological conformer prp(sc) requires contact between both isoforms and probably also requires a cellular factor, such as a nucleic acid or a glycosaminoglycan (gag). little is known about the structural features implicit in the gag-prp interaction. in the present work, light scattering, fluorescence, circular dichroism, and nuclear magnetic resonance (nmr) spectroscopy were used to describe the chemical and physical properties of the ... | 2010 | 21142149 |
| crucial role for prion protein membrane anchoring in the neuroinvasion and neural spread of prion infection. | in nature prion diseases are usually transmitted by extracerebral prion infection, but clinical disease results only after invasion of the central nervous system (cns). prion protein (prp), a host-encoded glycosylphosphatidylinositol (gpi)-anchored membrane glycoprotein, is necessary for prion infection and disease. here, we investigated the role of the anchoring of prp on prion neuroinvasion by studying various inoculation routes in mice expressing either anchored or anchorless prp. in control ... | 2010 | 21123371 |
| sex and prnp genotype determination in preimplantation caprine embryos. | the objective of this study was to test the accuracy of genotype diagnosis after whole amplification of dna extracted from biopsies obtained by trimming goat embryos and to evaluate the viability of biopsied embryos after vitrification/warming and transfer. whole genome amplification (wga) was performed using multiple displacement amplification (mda). sex and prion protein (prnp) genotypes were determined. sex diagnosis was carried out by pcr amplification of zfx/zfy and y chromosome-specific se ... | 2010 | 21121967 |
| neuropathological changes correlate temporally but not spatially with selected neuromodulatory responses in natural scrapie. | aim: neuropathological changes classically associated with sheep scrapie do not always correlate with clinical disease. we aimed to determine if selected neuromodulatory responses were altered during the course of the infection as it has been described in creutzfeldt-jakob disease and experimental bovine spongiform encephalopathy. methods: hemibrains from healthy sheep and natural scrapie cases at two stages of infection were examined for biochemical alterations related to the expression of type ... | 2010 | 21114681 |
| monitoring immune cells trafficking fluorescent prion rods hours after intraperitoneal infection. | presence of an abnormal form a host-encoded prion protein (prpc) that is protease resistant, pathologic and infectious characterizes prion diseases such as chronic wasting disease (cwd) of cervids and scrapie in sheep. the prion hypothesis asserts that this abnormal conformer constitutes most or all of the infectious prion. the role of the immune system in early events in peripheral prion pathogenesis has been convincingly demonstrated for cwd and scrapie. transgenic and pharmacologic studies in ... | 2010 | 21113122 |
| antigen retrieval using sodium hydroxide for prion immunohistochemistry in bovine spongiform encephalopathy and scrapie. | formalin-fixed and paraffin wax-embedded (ffpe) tissue sections are usually used for histopathological and immunohistochemical analyses in prion diseases in animals and man. however, formalin fixation cross-links proteins, reducing disease-associated prion protein (prp(sc)) immunolabelling. to detect prp(sc) in animals naturally affected with bovine spongiform encephalopathy (bse) and scrapie, we applied minimal pretreatment with sodium hydroxide (naoh). this simple pretreatment, combined with e ... | 2010 | 21112058 |
| generalized cerebral atrophy seen on mri in a naturally exposed animal model for creutzfeldt-jakob disease. | magnetic resonance imaging has been used in the diagnosis of human prion diseases such as scjd and vcjd, but patients are scanned only when clinical signs appear, often at the late stage of disease. this study attempts to answer the questions "could mri detect prion diseases before clinical symptoms appear?, and if so, with what confidence?" | 2010 | 21108848 |
| immunomodulation for prion and prion-related diseases. | prion diseases are a unique category of illness, affecting both animals and humans, where the underlying pathogenesis is related to a conformational change of a normal self protein called cellular prion protein to a pathological and infectious conformer known as scrapie prion protein (prp(sc)). currently, all prion diseases lack effective treatment and are universally fatal. past experiences with bovine spongiform encephalopathy and variant creutzfeldt-jakob disease mainly in europe, as well as ... | 2010 | 21105779 |
| intraspecies prion transmission results in selection of sheep scrapie strains. | sheep scrapie is caused by multiple prion strains, which have been classified on the basis of their biological characteristics in inbred mice. the heterogeneity of natural scrapie prions in individual sheep and in sheep flocks has not been clearly defined. | 2010 | 21103326 |
| high hydrophobic amino acid exposure is responsible of the neurotoxic effects induced by e200k or d202n disease-related mutations of the human prion protein. | mutations in prion protein are thought to be causative of inherited prion diseases favoring the spontaneous conversion of the normal prion protein into the scrapie-like pathological prion protein. we previously reported that, by controlled thermal denaturation, human prion protein fragment 90-231 acquires neurotoxic properties when transformed in a β-rich conformation, resembling the scrapie-like conformation. in this study we generated prion protein fragment 90-231 bearing mutations identified ... | 2010 | 21094273 |
| atypical scrapie/nor98 in a sheep from new zealand. | in a consignment of sheep brains from new zealand, to be used in europe as negative control material in scrapie rapid screening test evaluations, brain samples from 1 sheep (no. 1512) gave the following initially confusing results in various screening tests: the brainstem repeatedly produced negative results in 2 very similar screening kits (enzyme-linked immunosorbent assay [elisa]-1, elisa-2), a macerate made from brainstem and cerebellum returned a clearly positive result in elisa-2, and the ... | 2010 | 21088169 |
| sheep with scrapie and mastitis transmit infectious prions through the milk. | prions are misfolded proteins that are infectious and naturally transmitted, causing a fatal neurological disease in humans and animals. prion shedding routes have been shown to be modified by inflammation in excretory organs, such as the kidney. here, we show that sheep with scrapie and lentiviral mastitis secrete prions into the milk and infect nearly 90% of naïve suckling lambs. thus, lentiviruses may enhance prion transmission, conceivably sustaining prion infections in flocks for generation ... | 2010 | 21084475 |
| increased susceptibility of human-prp transgenic mice to bovine spongiform encephalopathy infection following passage in sheep. | the risk of the transmission of ruminant transmissible spongiform encephalopathy (tse) to humans was thought to be low due to the lack of association between sheep scrapie and the incidence of human tse. however, a single tse agent strain has been shown to cause both bovine spongiform encephalopathy (bse) and human vcjd, indicating that some ruminant tses are transmissible to humans. while the transmission of cattle bse to humans in transgenic mouse models has been inefficient, indicating the pr ... | 2010 | 21084466 |
| polymorphism of prion protein gene in sheep of inner mongolian, china. | susceptibility to natural scrapie in sheep is associated with polymorphisms at codons 136, 154 and 171 of the prion protein (prp) gene. to assess the risk of scrapie in sheep raised in china, dna from 30 sheep of two breeds was isolated, amplified and sequenced for the prp gene. the ovine prp gene was found to be highly homogenous. the genotype associated with high susceptibility to scrapie (vrq) was absent, whereas that associated with the resistance (arr) was present in 6.7% of sheep examined. ... | 2011 | 21063762 |
| ovine serum biomarkers of early and late phase scrapie. | transmissible spongiform encephalopathies are fatal neurodegenerative disease occurring in animals and humans for which no ante-mortem diagnostic test in biological fluids is available. in such pathologies, detection of the pathological form of the prion protein (i.e., the causative factor) in blood is difficult and therefore identification of new biomarkers implicated in the pathway of prion infection is relevant. | 2010 | 21044301 |
| enhanced enteric invasion of scrapie agents into the villous columnar epithelium via maternal immunoglobulin. | transmissible spongiform encephalopathies (tse) are caused by dietary oral exposure to infectious prion proteins (prpsc); however, the mechanism behind the uptake of prpsc in the intestines is poorly understood. in addition, epidemiological studies of bse showed that most cattle are exposed to the agents in the first 6 months of life, during the suckling and weaning periods. in the present study, to elucidate the enteric invasion mechanism of prions and to investigate the age-dependent transmiss ... | 2010 | 21042778 |
| early embryonic gene expression profiling of zebrafish prion protein (prp2) morphants. | the prion protein (prnp/prp) plays a crucial role in transmissible spongiform encephalopathies (tses) like creutzfeldt-jakob disease (cjd), scrapie and mad cow disease. notwithstanding the importance in human and animal disease, fundamental aspects of prnp/prp function and transmission remains unaccounted for. | 2010 | 21042590 |
| a bayesian hierarchical analysis to compare classical and atypical scrapie surveillance data; wales 2002-2006. | we describe the application of bayesian hierarchical models (bhm) to the analysis of risk of sheep scrapie using data from multiple surveillance sources. more specifically, we analysed data from the test results of three surveillance sources on classical and atypical scrapie in wales for the period 2002-2006. for each form of scrapie, a bhm was fitted to assess the occurrence of spatial patterns of risk shared by the multiple surveillance sources and the association between covariates and diseas ... | 2010 | 21040987 |
| scrapie; a disease of sheep; a review of the literature. | 1946 | 21015590 | |
| comparison studies of the structural stability of rabbit prion protein with human and mouse prion proteins. | prion diseases are fatal and infectious neurodegenerative diseases affecting humans and animals. rabbits are one of the few mammalian species reported to be resistant to infection from prion diseases isolated from other species (i. vorberg et al., journal of virology 77 (3) (2003) 2003-2009). thus the study of rabbit prion protein structure to obtain insight into the immunity of rabbits to prion diseases is very important. | 2010 | 20970434 |
| the interaction of ruminant prp(sc) with soils is influenced by prion source and soil type. | the persistence of prions within the environment is implicated in the horizontal transmission of ovine scrapie and cervid chronic wasting disease. description of the interaction of prion strains derived from their natural hosts with a range of soil types is imperative in understanding how prions persist in the environment and, therefore, the characteristics of prion transmission. here, we demonstrate that all detectable ovine scrapie and bovine bse prp(sc) bind to a range of soil types within 24 ... | 2010 | 20968294 |
| hsp70 binds to prpc in the process of prpc release via exosomes from thp-1 monocytes. | prpc (cellular prion protein) is a gpi (glycophosphatidylinositol)-anchored protein present on the surface of a number of peripheral blood cells. prpc must be present for the generation and propagation of pathogenic conformer [prpsc (scrapie prion protein)], which is a conformational conversion form of prpc and has a central role in transmissible spongiform encephalopathies. it is important to determine the transportation mechanism of normal prpc between cells. exosomes are membrane vesicles rel ... | 2011 | 20964628 |
| identification and structural analysis of c-terminally truncated collapsin response mediator protein-2 in a murine model of prion diseases. | abstract: | 2010 | 20961402 |
| prion replication in the hematopoietic compartment is not required for neuroinvasion in scrapie mouse model. | fatal neurodegenerative prion diseases are caused by the transmissible prp(sc) prion agent whose initial replication after peripheral inoculation takes place in follicular dendritic cells present in germinal centers of lymphoid organs. however, prion replication also occurs in lymphoid cells. to assess the role of the hematopoietic compartment in neuroinvasion and prion replication, we generated chimeric mice, on a uniform congenic c57/bl6j background, by bone marrow replacement with hematopoiet ... | 2010 | 20957200 |
| sulfated dextrans enhance in vitro amplification of bovine spongiform encephalopathy prp(sc) and enable ultrasensitive detection of bovine prp(sc). | prions, infectious agents associated with prion diseases such as creutzfeldt-jakob disease in humans, bovine spongiform encephalopathy (bse) in cattle, and scrapie in sheep and goats, are primarily comprised of prp(sc), a protease-resistant misfolded isoform of the cellular prion protein prp(c). protein misfolding cyclic amplification (pmca) is a highly sensitive technique used to detect minute amounts of scrapie prp(sc). however, the current pmca technique has been unsuccessful in achieving goo ... | 2010 | 20957174 |
| solution structure and dynamics of the i214v mutant of the rabbit prion protein. | the conformational conversion of the host-derived cellular prion protein (prp(c)) into the disease-associated scrapie isoform (prp(sc)) is responsible for the pathogenesis of transmissible spongiform encephalopathies (tses). various single-point mutations in prp(c)s could cause structural changes and thereby distinctly influence the conformational conversion. elucidation of the differences between the wild-type rabbit prp(c) (raprp(c)) and various mutants would be of great help to understand the ... | 2010 | 20949107 |
| prion transmission: prion excretion and occurrence in the environment. | prion diseases range from being highly infectious, for example scrapie and cwd, which show facile transmission between susceptible individuals, to showing negligible horizontal transmission, such as bse and cjd, which are spread via food or iatrogenically, respectively. scrapie and cwd display considerable in vivo dissemination, with prp(sc) and infectivity being found in a range of peripheral tissues. this in vivo dissemination appears to facilitate the recently reported excretion of prion thro ... | 2010 | 20948292 |
| a novel class of potential prion drugs: preliminary in vitro and in vivo data for multilayer coated gold nanoparticles. | gold nanoparticles coated with oppositely charged polyelectrolytes, such as polyallylamine hydrochloride and polystyrenesulfonate, were examined for potential inhibition of prion protein aggregation and prion (prpsc) conversion and replication. different coatings, finishing with a positive or negative layer, were tested, and different numbers of layers were investigated for their ability to interact and reduce the accumulation of prpsc in scrapie prion infected scgt1 and scn2a cells. the particl ... | 2010 | 20944860 |
| differentiation of ruminant transmissible spongiform encephalopathy isolate types, including bovine spongiform encephalopathy and ch1641 scrapie. | with increased awareness of the diversity of transmissible spongiform encephalopathy (tse) strains in the ruminant population, comes an appreciation of the need for improved methods of differential diagnosis. exposure to bovine spongiform encephalopathy (bse) has been associated with the human tse, variant creutzfeldt-jakob disease, emphasizing the necessity in distinguishing low-risk tse types from bse. tse type discrimination in ruminants such as cattle, sheep, goats and deer, requires the app ... | 2010 | 20943889 |
| bse infectivity in the absence of detectable prp(sc) accumulation in the tongue and nasal mucosa of terminally diseased cattle. | the pathogenesis of bovine spongiform encephalopathy (bse) infections in cattle has been studied in recent years by using highly sensitive transgenic-mouse bioassays. it has been shown that in this species, the bse agent amplifies almost exclusively in the central and peripheral nervous system. even in animals that were killed in the clinical end stage of the disease, the lymphoreticular system was shown to be free of the infectious agent. no other animal species investigated to date exhibits su ... | 2010 | 20943888 |
| membrane interactions and conformational preferences of human and avian prion n-terminal tandem repeats: the role of copper(ii) ions, ph, and membrane mimicking environments. | the flexible n-terminal domain of the prion protein (prp(c)) is believed to play a pivotal role in both trafficking of the protein through the cell membrane and its pathogenic conversion into the β sheet-rich scrapie isoform (prp(sc)). unlike mammalian prp(c), avian prion proteins are not known to undergo any pathogenic conformational conversions. consequently, some critical advances in our understanding of the molecular mechanisms underlying prion pathogenesis are expected from comparative stud ... | 2010 | 20936829 |
| prion protein self-interactions: a gateway to novel therapeutic strategies? | transmissible spongiform encephalopathies (tses) or prion diseases are fatal neurodegenerative disorders and include among others creutzfeldt-jakob disease in humans, bovine spongiform encephalopathy (bse) in cattle, and scrapie in sheep. the central event in disease development in tses is the refolding of the normal host-encoded cellular prion protein (prp) into abnormal and disease associated prion protein. the agent is thought to consist mainly or exclusively of these pathologically folded pr ... | 2010 | 20932496 |
| expression and knockdown of cellular prion protein (prpc) in differentiating mouse embryonic stem cells. | the mammalian cellular prion protein (prp(c)) is a highly conserved glycoprotein that may undergo conversion into a conformationally altered isoform (scrapie prion protein or prp(sc)), widely believed to be the pathogenic agent of transmissible spongiform encephalopathies (tses). although much is known about pathogenic prp conversion and its role in tses, the normal function of prp(c) is poorly understood. given the abundant expression of prp(c) in the developing mammalian cns and the spatial as ... | 2011 | 20926176 |
| prion genotypes of scrapie-infected canadian sheep 1998-2008. | this report describes the genetics of the prion protein gene (prnp) at codons 136, 154, and 171 for sheep diagnosed with naturally acquired classical scrapie in canada between 1998 and 2008. genotyping analysis was performed on 249 sheep with confirmed classical scrapie infection representing 98 flocks from 6 provinces. a further case-control analysis of 3 of these flocks compared the genotypes between infected sheep (n = 72) and those of their healthy flockmates (n = 1990). the incidence of cla ... | 2010 | 20885849 |
| marked influence of the route of infection on prion strain apparent phenotype in a scrapie transgenic mouse model. | prion strains yield specific neuropathological features including spongiform degeneration and deposition patterns of pathological prion protein. their invariant regional distribution, following variations in the infection route, has led to the proposal that prions replicate preferentially in defined neuro-anatomical areas. the molecular mechanisms underlying this apparent strain-specific neuronal tropism are currently unknown. however, a possible explanation may be that prion replication is rela ... | 2010 | 20875860 |
| amyloid structure and assembly: insights from scanning transmission electron microscopy. | amyloid fibrils are filamentous protein aggregates implicated in several common diseases such as alzheimer's disease and type ii diabetes. similar structures are also the molecular principle of the infectious spongiform encephalopathies such as creutzfeldt-jakob disease in humans, scrapie in sheep, and of the so-called yeast prions, inherited non-chromosomal elements found in yeast and fungi. scanning transmission electron microscopy (stem) is often used to delineate the assembly mechanism and s ... | 2010 | 20868754 |
| capacity of the manufacturing process of flebogamma(®) dif, a new human high purity intravenous immunoglobulin, to remove a tse model-agent. | the variant creutfeldt-jakob disease (vcjd) is a transmissible spongiform encephalopathy (tse) associated with the ingestion of cattle derived products affected with bovine spongiform encephalopathy. vcjd emerged in the uk, where most of the cases occurred (170 of 217 cases worldwide). manufacturers of biological products must investigate the ability of their production processes to remove tse agents. two manufacturing steps (polyethylene glycol-peg precipitation and nanofiltration down to 20 nm ... | 2010 | 20863716 |
| cartilaginous metaplasia in the sclera of suffolk sheep. | scleral cartilaginous metaplasia was detected by routine histologic examination of globes from 5 suffolk sheep from a scrapie pathogenesis study. the extent of the metaplasia varied among the sheep but was always posterior to the tapetal fundus. the matrix surrounding chondrocytes stained intensely with alcian blue and was immunopositive for type ii collagen. retrospective evaluation of additional eyes from suffolk and cheviot sheep used in various scrapie pathogenesis studies at the authors' fa ... | 2010 | 20861498 |
| transcytosis of murine-adapted bovine spongiform encephalopathy agents in an in vitro bovine m cell model. | transmissible spongiform encephalopathies (tse), including bovine spongiform encephalopathy (bse), are fatal neurodegenerative disorders in humans and animals. bse appears to have spread to cattle through the consumption of feed contaminated with bse/scrapie agents. in the case of an oral infection, the agents have to cross the gut-epithelial barrier. we recently established a bovine intestinal epithelial cell line (bie cells) that can differentiate into the m cell type in vitro after lymphocyti ... | 2010 | 20861256 |
| a new method for the characterization of strain-specific conformational stability of protease-sensitive and protease-resistant prp. | although proteinacious in nature, prions exist as strains with specific self-perpetuating biological properties. prion strains are thought to be associated with different conformers of prp(sc), a disease-associated isoform of the host-encoded cellular protein (prp(c)). molecular strain typing approaches have been developed which rely on the characterization of protease-resistant prp(sc). however, prp(sc) is composed not only of protease-resistant but also of protease-sensitive isoforms. the aim ... | 2010 | 20856860 |
| molecular characterization of the full-length coding sequence of the caprine laminin receptor gene (rpsa). | scrapie is a prion disease in sheep and goats. ribosomal protein sa (rpsa), also called 37 kda laminin receptor precursor/67 kda laminin receptor has been demonstrated to be a putative cell surface receptor for prion. to investigate the caprine rpsa, we cloned the full-length coding sequence of the gene of goat and submitted it to genbank. the length of the open reading frame is 888 bp, encoding 295 amino acids. the putative amino acid sequence is highly similar to that of other mammals. the cap ... | 2010 | 20839046 |
| cytosolic prp induces apoptosis of cell by disrupting microtubule assembly. | prion protein (prp) is able to bind with tubulin and to interfere with the formation of microtubule. to investigate the influence of accumulation of cytosolic prp in cytoplasm on microtubule, plasmid pcdna3.1-prp23-230 expressing human prp23-230 was introduced into hela cells. immunoprecipitation assays identified the molecular interaction between cytosolic prp and cellular tubulin. confocal microscopy showed the co-localization of the expressed cytosolic prp with tubulin in cytoplasm. immunoflu ... | 2011 | 20838930 |
| early noninvasive diagnosis of neurodegenerative diseases. | this paper reviews the contemporary trends in the pathobiochemistry of neurodegenerative disorders with respect to their early predictive diagnosis and possible treatment interventions. if we consider the current epidemiological data related to neurodegenerative disorders, medicine is going to face in the near future latent pandemic situations. the introduction puts an emphasis on the emerging importance of one major cluster of neurodegenerative disorders: diseases of the abnormal protein beta-c ... | 2010 | 20836391 |
| transport of the pathogenic prion protein through soils. | transmissible spongiform encephalopathies (tses) are progressive neurodegenerative diseases and include bovine spongiform encephalopathy of cattle, chronic wasting disease (cwd) of deer and elk, scrapie in sheep and goats, and creutzfeldt-jakob disease in humans. an abnormally folded form of the prion protein (designated prp(tse)) is typically associated with tse infectivity and may constitute the major, if not sole, component of the infectious agent. transmission of cwd and scrapie is mediated ... | 2010 | 20830901 |
| a drosophila model of gss syndrome suggests defects in active zones are responsible for pathogenesis of gss syndrome. | we have established a drosophila model of gerstmann-sträussler-scheinker (gss) syndrome by expressing mouse prion protein (prp) having leucine substitution at residue 101 (moprp(p101l)). flies expressing moprp(p101l), but not wild-type moprp (moprp(3f4)), showed severe defects in climbing ability and early death. expressed moprp(p101l) in drosophila was differentially glycosylated, localized at the synaptic terminals and mainly present as deposits in adult brains. we found that behavioral defect ... | 2010 | 20829230 |
| prion strain interactions are highly selective. | various misfolded and aggregated neuronal proteins commonly coexist in neurodegenerative disease, but whether the proteins coaggregate and alter the disease pathogenesis is unclear. here, we used mixtures of distinct prion strains, which are believed to differ in conformation, to test the hypothesis that two different aggregates interact and change the disease in vivo. we tracked two prion strains in mice histopathologically and biochemically, as well as by spectral analysis of plaque-bound ptaa ... | 2010 | 20826672 |
| digestion and transportation of bovine spongiform encephalopathy-derived prion protein in the sheep intestine. | bovine spongiform encephalopathy (bse) is acquired orally and the mechanisms involved in the absorption and transportation of infectivity across the gut wall are therefore critical. isolated gut loops were created in lambs, massaged to remove intestinal contents (flushed) or left non-flushed, inoculated with cattle bse homogenate and excised at different time-points. gut loops were examined by immunohistochemistry (ihc) for disease-associated prion protein (prp(d)), and the contents were analyse ... | 2010 | 20826616 |
| sequence-dependent prion protein misfolding and neurotoxicity. | prion diseases are neurodegenerative disorders caused by misfolding of the normal prion protein (prp) into a pathogenic "scrapie" conformation. to better understand the cellular and molecular mechanisms that govern the conformational changes (conversion) of prp, we compared the dynamics of prp from mammals susceptible (hamster and mouse) and resistant (rabbit) to prion diseases in transgenic flies. we recently showed that hamster prp induces spongiform degeneration and accumulates into highly ag ... | 2010 | 20817727 |
| detection of prp(sc) in formalin-fixed, paraffin-embedded tissue by western blot differentiates classical scrapie, nor98 scrapie, and bovine spongiform encephalopathy. | transmissible, spongiform encephalopathies including bovine spongiform encephalopathy (bse) and scrapie are fatal neurodegenerative disorders associated with the presence of an infectious abnormal isoform of normal mammalian proteins called prions. identification of the prion protein associated with scrapie (prp(sc)) in the central nervous system is typically based upon immunoassays including immunohistochemistry (ihc) using formalin-fixed tissues or western blot (wb) assays using fresh and/or f ... | 2010 | 20807921 |
| synthesis and anti-prion activity evaluation of aminoquinoline analogues. | transmissible spongiform encephalopathies form a group of neurodegenerative diseases that affect humans and other mammals. they occur when the native prion protein is converted into an infectious isoform, the scrapie prp, which aggregates, leading to neurodegeneration. although several compounds were evaluated for their ability to inhibit this conversion, there is no effective therapy for such diseases. previous studies have shown that antimalarial compounds, such as quinolines, possess anti-scr ... | 2010 | 20797807 |
| environmental sources of scrapie prions. | ovine scrapie and cervine chronic wasting disease show considerable horizontal transmission. here we report that a scrapie-affected sheep farm has a widespread environmental contamination with prions. prions were amplified by protein-misfolding cyclic amplification (spmca) from seven of nine environmental swab samples taken, including those from metal, plastic, and wooden surfaces. sheep had been removed from the areas from which the swabs were taken up to 20 days prior to sampling, indicating t ... | 2010 | 20739536 |
| plasminogen stimulates propagation of protease-resistant prion protein in vitro. | to clarify the role of plasminogen as a cofactor for prion propagation, we conducted functional assays using a cell-free prion protein (prp) conversion assay termed protein misfolding cyclic amplification (pmca) and prion-infected cell lines. here, we report that plasminogen stimulates propagation of the protease-resistant scrapie prp (prp(sc)). compared to control pmca conducted without plasminogen, addition of plasminogen in pmca using wild-type brain material significantly increased prp conve ... | 2010 | 20732953 |
| pruritus in familial creutzfeldt-jakob disease: a common symptom associated with central nervous system pathology. | pruritus, a common feature of animal prion diseases such as scrapie, is rarely reported in humans with creutzfeldt-jakob disease (cjd), and its anatomical background is not well defined. the present study was undertaken to carry out a methodical prospective search for the prevalence of pruritus in cjd patients and investigate its anatomical substrate by mri. the study group included consecutive familial and sporadic cjd patients carrying the e200k prnp mutation followed up in a longitudinal pros ... | 2011 | 20725737 |
| peg-interspersed nitrilotriacetic acid-functionalized quantum dots for site-specific labeling of prion proteins expressed on cell surfaces. | a strategy has been put forward to fabricate peg-interspersed nitrilotriacetic acid (nta)-functionalized qds by one-step self-assembly using a mixture of self-synthesized nta-terminated amphiphilic polymer and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-n-[carboxy(polyethylene glycol)2000] (dspe-peg-cooh). the process was highly reproducible for facile functionalization of qds via simultaneous self-assembly of biocompatible peg molecules onto their surface. an optimized molar ratio of nta-te ... | 2010 | 20723972 |
| the h187r mutation of the human prion protein induces conversion of recombinant prion protein to the prp(sc)-like form. | prion diseases are associated with a conformational switch in the prion protein (prp) from its normal cellular form (denoted prp(c)) to a disease-associated "scrapie" form (prp(sc)). a number of prp(sc)-like conformations can be generated by incubating recombinant prp(c) at low ph, indicating that protonation of key residues is likely to destabilize prp(c), facilitating its conversion to prp(sc). here, we examine the stability of human prp(c) with ph and find that prp(c) fold stability is signif ... | 2010 | 20718410 |
| a partially folded state of ovalbumin at low ph tends to aggregate. | at ph 2, ovalbumin retains native-like secondary structure as seen by far-uv cd and ftir, but lacks well-defined tertiary structure as seen by the fluorescence and near-uv cd spectra. addition of 20 mm trifluoroacetic acid (tfa) or 30 mm trichloroacetic acid (tca) on acid-induced state results in protein aggregation. this aggregated state possesses extensive β-sheet structure as revealed by far-uv cd and ftir spectroscopy. furthermore, the aggregates exhibit decreased ans fluorescence and increa ... | 2011 | 20703954 |
| aberrant erk 1/2 complex activation and localization in scrapie-infected gt1-1 cells. | abstract: | 2010 | 20696038 |
| a "shotgun" method for tracing the birth locations of sheep from flock tags, applied to scrapie surveillance in great britain. | movement records are often used to identify animal sample provenance by retracing the movements of individuals. here we present an alternative method, which uses the same identity tags and movement records as are used to retrace movements, but ignores individual movement paths. the first step uses a simple query to identify the most likely birth holding for every identity tag included in a database recording departures from agricultural holdings. the second step rejects a proportion of the birth ... | 2010 | 20692059 |
| an assessment of the efficiency of prpsc detection in rectal mucosa and third-eyelid biopsies from animals infected with scrapie. | in classical scrapie, detection of prpsc on lymphoreticular system is used for the in vivo and post mortem diagnosis of the disease. however, the sensitivity of this methodology is not well characterised because the magnitude and duration of lymphoid tissue involvement can vary considerably. the aim of the present study was to evaluate the efficiency of detecting prpsc in rectal mucosa and third-eyelid biopsies. a total of 474 genetically susceptible sheep and 24 goats from three scrapie infecte ... | 2011 | 20685048 |
| glypican-1 facilitates prion conversion in lipid rafts. | the conformational conversion of the cellular prion protein (prp(c)) to the infectious form (prp(sc)) is the critical step in the pathogenesis of prion diseases such as creutzfeldt-jakob disease in humans and scrapie in sheep. cholesterol-rich lipid rafts play a key role in the conversion of prp(c) to prp(sc) and other cellular components have been identified as important cofactors to trigger, enhance, or accelerate prion formation. amongst these heparan sulphate proteoglycans (hspgs) and their ... | 2011 | 20681952 |
| nmr structure of the human prion protein with the pathological q212p mutation reveals unique structural features. | prion diseases are fatal neurodegenerative disorders caused by an aberrant accumulation of the misfolded cellular prion protein (prp(c)) conformer, denoted as infectious scrapie isoform or prp(sc). in inherited human prion diseases, mutations in the open reading frame of the prp gene (prnp) are hypothesized to favor spontaneous generation of prp(sc) in specific brain regions leading to neuronal cell degeneration and death. here, we describe the nmr solution structure of the truncated recombinant ... | 2010 | 20661422 |
| spontaneous generation of mammalian prions. | prions are transmissible agents that cause lethal neurodegeneration in humans and other mammals. prions bind avidly to metal surfaces such as steel wires and, when surface-bound, can initiate infection of brain or cultured cells with remarkable efficiency. while investigating the properties of metal-bound prions by using the scrapie cell assay to measure infectivity, we observed, at low frequency, positive assay results in control groups in which metal wires had been coated with uninfected mouse ... | 2010 | 20660771 |
| biochemical and immunohistochemical characterization of feline spongiform encephalopathy in a german captive cheetah. | feline spongiform encephalopathy (fse) is a transmissible spongiform encephalopathy that affects domestic cats (felis catus) and captive wild members of the family felidae. in this report we describe a case of fse in a captive cheetah from the zoological garden of nuremberg. the biochemical examination revealed a bse-like pattern. disease-associated scrapie prion protein (prp(sc)) was widely distributed in the central and peripheral nervous system, as well as in the lymphoreticular system and in ... | 2010 | 20660146 |
| neuroinvasion in prion diseases: the roles of ascending neural infection and blood dissemination. | prion disorders are infectious, neurodegenerative diseases that affect humans and animals. susceptibility to some prion diseases such as kuru or the new variant of creutzfeldt-jakob disease in humans and scrapie in sheep and goats is influenced by polymorphisms of the coding region of the prion protein gene, while other prion disorders such as fatal familial insomnia, familial creutzfeldt-jakob disease, or gerstmann-straussler-scheinker disease in humans have an underlying inherited genetic basi ... | 2010 | 20652006 |
| prp(sc) is associated with b cells in the blood of scrapie-infected sheep. | recently, we reported that prp(sc), a surrogate marker for prion disease, is associated with the cellular fraction of blood from scrapie-infected sheep using a ligand-based immunoassay. in the study reported here, we found that a subset of peripheral blood mononuclear cells is most likely to sequester prp(sc) during both the preclinical phase of disease and at clinical end point. these cells had a cell surface phenotype of mhc class ii dq(+), surface immunoglobulin(+), cd11b(+), cd11c(+), cd21(+ ... | 2010 | 20646730 |
| paradoxical role of prion protein aggregates in redox-iron induced toxicity. | imbalance of iron homeostasis has been reported in sporadic creutzfeldt-jakob-disease (scjd) affected human and scrapie infected animal brains, but the contribution of this phenotype to disease associated neurotoxicity is unclear. | 2010 | 20625431 |
| a case-control study of atypical scrapie in gb sheep flocks. | wide-scale scrapie surveillance started in 2002 in the eu. as a result, a new form of scrapie was detected which has been referred to as atypical scrapie. here we present a case-control study conducted on british sheep farms to increase our understanding of the disease and potential risk factors at holding level. forty case and 120 control holdings were traced from the confirmed atypical results in the scrapie surveillance programme in great britain during the period 2002-2007. a detailed questi ... | 2010 | 20615563 |
| [cellular prion protein in the central nervous system of mammals. anatomoclinical associations]. | the scrapie prion protein (prpsc) requires the cellular prion protein (prpc) for its propagation and replication. in this work we studied the expression and localization of the prpc in the central nervous system (snc) of the rat, mouse, cat, cow and human, using immunohistochemistry and western blot techniques to understand more about prionopathies and alzheimer's disease (ea). | 2010 | 20609300 |
| risk of escape of prions in gaseous emissions from on-farm digestion vessels. | 2010 | 20605957 | |
| prion interaction with the 37-kda/67-kda laminin receptor on enterocytes as a cellular model for intestinal uptake of prions. | enterocytes, a major cell population of the intestinal epithelium, represent one possible barrier to the entry of prions after oral exposure. we established a cell culture system employing enterocytes from different species to study alimentary prion interaction with the 37-kda/67-kda laminin receptor lrp/lr. human, bovine, porcine, ovine, and cervid enterocytes were cocultured with brain homogenates from cervid, sheep, and cattle suffering from chronic wasting disease (cwd), scrapie, and bovine ... | 2010 | 20603132 |
| the discovery of misfolded prions as an infectious agent. | 2010 | 20594190 | |
| sex effect in mouse and human prion disease. | sex effect on the incubation period of variant creutzfeldt-jakob disease (vcjd) disease in human and me-7 murine models was investigated. in the 167 vcjd cases reported in the united kingdom as of january 2009, age at onset was significantly lower in female patients (by 2 years) than in male patients after stratification on birth cohort. in c57/bl6n mice infected with me-7 scrapie strain, incubation was shorter in female than in male mice. the incubation period increased in castrated male mice a ... | 2010 | 20594106 |
| gene expression analysis in distinct regions of the central nervous system during the development of ssbp/1 sheep scrapie. | rodent scrapie models have been exploited to define the molecular basis for the progression of neuropathological changes in tse diseases. we aim to assess whether cns gene expression changes consistently observed in mouse models are of generic relevance, for example to natural tse diseases, or are tse strain, host species or brain region specific. six genes, representing distinct physiological pathways and showing consistent changes in expression levels with disease progression in murine scrapie ... | 2011 | 20576367 |
| use of a preclinical test in the control of classical scrapie. | scrapie control in great britain (gb) was originally based on the national scrapie plan's ram genotyping scheme aimed at reducing the susceptibility of the national flock. the current official strategy to control scrapie in the national flock involves culling susceptible genotypes in individual, known affected flocks (compulsory scrapie flock scheme or csfs). however, the recent development of preclinical test candidates means that a strategy based on disease detection may now be feasible. here, ... | 2010 | 20573855 |
| sensitive detection of scrapie prion protein in soil. | prion diseases are fatal neurodegenerative disorders that are caused by infectious agents known as prions. prions are composed primarily of the pathogenic prion protein isoform, prp(sc). because significant levels of infectivity have been detected in excrement from animals infected with scrapie and chronic wasting disease, studies on the dynamics of prp(sc) levels in contaminated soil are needed to assess the possible horizontal transmission of prion diseases. using protein misfolding cyclic amp ... | 2010 | 20570651 |
| immunohistochemical study of macrophage and cytokine dynamics in the gut of scrapie-infected mice. | to study numerical changes in intestinal macrophages and variations in cytokine production by immune cells in the intestine, conventional c57bl/6j mice were orally infected with the rocky mountain laboratory strain of scrapie. animals were sacrificed at different timepoints, and samples were taken and processed by routine methods for morphological and immunohistochemical analysis. the results point to a possible role for macrophages in the uptake and transport of the infective agent to peyer's p ... | 2010 | 20552553 |
| variability in disease phenotypes within a single prnp genotype suggests the existence of multiple natural sheep scrapie strains within europe. | variability of pathological phenotypes within classical sheep scrapie cases has been reported for some time, but in many instances it has been attributed to differences in the prnp genotype of the host. to address this issue we have examined by immunohistochemistry (ihc) and western blotting (wb) for the disease-associated form of the prion protein (prp(d)), the brains of 23 sheep from five european countries, all of which were of the same arq/arq genotype. as a result of ihc examinations, sheep ... | 2010 | 20538906 |
| cellular and sub-cellular pathology of animal prion diseases: relationship between morphological changes, accumulation of abnormal prion protein and clinical disease. | the transmissible spongiform encephalopathies (tses) or prion diseases of animals are characterised by cns spongiform change, gliosis and the accumulation of disease-associated forms of prion protein (prp(d)). particularly in ruminant prion diseases, a wide range of morphological types of prp(d) depositions are found in association with neurons and glia. when light microscopic patterns of prp(d) accumulations are correlated with sub-cellular structure, intracellular prp(d) co-localises with lyso ... | 2011 | 20532540 |
| cell-based quantification of chronic wasting disease prions. | cell-based measurement of prion infectivity is currently restricted to experimental strains of mouse-adapted scrapie. having isolated cell cultures with susceptibility to prions from diseased elk, we describe a modification of the scrapie cell assay allowing evaluation of prions causing chronic wasting disease, a naturally occurring transmissible spongiform encephalopathy. we compare this cervid prion cell assay to bioassays in transgenic mice, the only other existing method for quantification, ... | 2010 | 20519392 |
| comparative profiling of highly enriched 22l and chandler mouse scrapie prion protein preparations. | transmissible spongiform encephalopathies (tses) or prion diseases are characterized by the accumulation of an aggregated isoform of the prion protein (prp). this pathological isoform, termed prp(sc), appears to be the primary component of the tse infectious agent or prion. however, it is not clear to what extent other protein cofactors may be involved in tse pathogenesis or whether there are prp(sc)-associated proteins which help to determine tse strain-specific disease phenotypes. we enriched ... | 2010 | 20518029 |
| estimating prion concentration in fluids and tissues by quantitative pmca. | prions, the proteinaceous infectious agent responsible for prion diseases, can be detected with high sensitivity by protein misfolding cyclic amplification (pmca) technology. here we describe a quantitative pmca procedure to calculate the concentration of very low levels of prions in biological samples. using this procedure, we determined the quantities of misfolded prion protein (prp(sc)) in brain, spleen, blood and urine of scrapie-affected hamsters. | 2010 | 20512142 |
| calnexin inhibits thermal aggregation and neurotoxicity of prion protein. | prion diseases are fatal neurodegenerative disorder associated with the conversion of the cellular isoform of the prion protein (prp(c)) into the infectious scrapie isoform (prp(sc)). deposition of misfolded prion proteins (prp) on certain regions of brain can result in prion diseases. as a membrane-bound chaperone of the endoplasmic reticulum (er), calnexin ensures the proper folding and quality control of newly synthesized proteins. using purified components in vitro, calnexin associated with ... | 2010 | 20506117 |
| the distribution of four trace elements (fe, mn, cu, zn) in forage and the relation to scrapie in iceland. | previous studies indicated that the iron (fe)/manganese (mn) ratio in forage of sheep was significantly higher on scrapie-afflicted farms than on farms in other scrapie categories. this study was conducted to examine whether fe and mn in forage of sheep varied in general according to the scrapie status of different areas in the country. copper (cu) and zinc (zn) were also included because of a possible relation to scrapie. | 2010 | 20492671 |
| quantitative estimation of genetic risk for atypical scrapie in french sheep and potential consequences of the current breeding programme for resistance to scrapie on the risk of atypical scrapie. | since 2002, active surveillance programmes have detected numerous atypical scrapie (as) and classical scrapie cases (cs) in french sheep with almost all the prp genotypes. the aim of this study was 1) to quantify the genetic risk of as in french sheep and to compare it with the risk of cs, 2) to quantify the risk of as associated with the increase of the arr allele frequency as a result of the current genetic breeding programme against cs. | 2010 | 20482755 |
| scrapie prevalence in sheep of susceptible genotype is declining in a population subject to breeding for resistance. | susceptibility of sheep to scrapie infection is known to be modulated by the prp genotype of the animal. in the netherlands an ambitious scrapie control programme was started in 1998, based on genetic selection of animals for breeding. from 2002 onwards eu regulations required intensive active scrapie surveillance as well as certain control measures in affected flocks.here we analyze the data on genotype frequencies and scrapie prevalence in the dutch sheep population obtained from both surveill ... | 2010 | 20470415 |
| association of n176k and l141f dimorphisms of the prnp gene with lack of pathological prion protein deposition in placentas of naturally and experimentally scrapie-affected arq/arq sheep. | the placenta is important in the horizontal transmission of the aetiological agent in scrapie-affected sheep. it has been demonstrated that the placentas of fetuses carrying the dimorphism q171r of the prnp gene is resistant to pathological prion protein (prp(sc)) accumulation in the placenta. to test whether other prnp polymorphisms are associated with a lack of placental prp(sc) deposition, we carried out a study on 26 naturally and 11 experimentally scrapie-affected ewes with or without clini ... | 2010 | 20463148 |
| horse prion protein nmr structure and comparisons with related variants of the mouse prion protein. | the nmr structure of the horse (equus caballus) cellular prion protein at 25 degrees c exhibits the typical prp(c) [cellular form of prion protein (prp)] global architecture, but in contrast to most other mammalian prp(c)s, it contains a well-structured loop connecting the beta2 strand with the alpha2 helix. comparison with designed variants of the mouse prion protein resulted in the identification of a single amino acid exchange within the loop, d167s, which correlates with the high structural ... | 2010 | 20460128 |
| identification of atypical scrapie in canadian sheep. | scrapie, a transmissible spongiform encephalopathy of sheep and goats, exists in most small ruminant-producing countries of the world. a novel form of this disease was recently recognized and is known by various names, including nor98, nor98-like, and atypical scrapie. differing from classic scrapie in epidemiology, histopathology, and biochemical characteristics, atypical scrapie cases have been identified throughout europe and in the united states. enhanced scrapie surveillance efforts recentl ... | 2010 | 20453215 |
| enzymatic digestion of chronic wasting disease prions bound to soil. | chronic wasting disease (cwd) and sheep scrapie can be transmitted via indirect environmental routes, and it is known that soil can serve as a reservoir of prion infectivity. given the strong interaction between the prion protein (prp) and soil, we hypothesized that binding to soil enhances prion resistance to enzymatic digestion, thereby facilitating prion longevity in the environment and providing protection from host degradation. we characterized the performance of a commercially available su ... | 2010 | 20450190 |
| relevance of oral experimental challenge with classical scrapie in sheep. | oral inoculation is currently considered as the best approach to mimic natural tse contamination in ruminants. in this study, we compared the timing of abnormal prion protein (prp(sc)) dissemination and accumulation in the organism of susceptible sheep either orally inoculated or naturally infected with classical scrapie. both animal groups shared a similar prp(sc) dissemination scheme and accumulation dynamics in lymphoid tissues. however, orally challenged animals displayed an earlier neuro-in ... | 2010 | 20444991 |
| eradication of scrapie with selective breeding: are we nearly there? | following eu decision 2003/100/ec member states have recently implemented sheep breeding programmes to reduce the prevalence of sheep with tse susceptible prion genotypes. the present paper investigates the progress of the breeding programme in the netherlands. the prp genotype frequencies were monitored through time using two sets of random samples: one set covers the years 2005 to 2008 and is taken from national surveillance programme; the other is taken from 168 random sheep farms in 2007. th ... | 2010 | 20441587 |