Publications
| Title | Abstract | Year Filter | PMID(sorted descending) Filter |
|---|
| gene expression profile of quinacrine-cured prion-infected mouse neuronal cells. | prion diseases are transmissible fatal neurodegenerative diseases of humans and animals, characterised by the presence of an abnormal isoform (scrapie prion protein; prp(sc)) of the endogenous cellular prion protein (prp(c)). the pathological mechanisms at the basis of prion diseases remain elusive, although the accumulation of prp(sc) has been linked to neurodegeneration. different genomic approaches have been applied to carry out large-scale expression analysis in prion-infected brains and cel ... | 2008 | 18036195 |
| prion strain discrimination using luminescent conjugated polymers. | the occurrence of multiple strains of prions may reflect conformational variability of prp(sc), a disease-associated, aggregated variant of the cellular prion protein, prp(c). here we used luminescent conjugated polymers (lcps), which emit conformation-dependent fluorescence spectra, for characterizing prion strains. lcp reactivity and emission spectra of brain sections discriminated among four immunohistochemically indistinguishable, serially mouse-passaged prion strains derived from sheep scra ... | 2007 | 18026110 |
| in vivo depletion of cd11c+ cells impairs scrapie agent neuroinvasion from the intestine. | following oral exposure, some transmissible spongiform encephalopathy (tse) agents accumulate first upon follicular dendritic cells (dcs) in the galt. studies in mice have shown that tse agent accumulation in the galt, in particular the peyer's patches, is obligatory for the efficient transmission of disease to the brain. however, the mechanism through which tse agents are initially conveyed from the gut lumen to the galt is not known. studies have implicated migratory hemopoietic dcs in this pr ... | 2007 | 18025222 |
| demographic risk factors for classical and atypical scrapie in great britain. | following the bovine spongiform encephalopathy (bse) crisis, the european union has introduced policies for eradicating transmissible spongiform encephalopathies (tses), including scrapie, from large ruminants. however, recent european union surveillance has identified a novel prion disease, 'atypical' scrapie, substantially different from classical scrapie. it is unknown whether atypical scrapie is naturally transmissible or zoonotic, like bse. furthermore, cases have occurred in scrapie-resist ... | 2007 | 18024920 |
| prion propagation in a nerve conduit model containing segments devoid of axons. | prions, the putative causative agents of transmissible spongiform encephalopathies, are neurotropic pathogens that spread to the central nervous system via synaptically linked neural conduits upon peripheral infection. axons and their transport processes have been suggested as mediators of nerve-associated prion dissemination. however, the exact cellular components and molecular mechanisms underlying neural spread are unknown. this study used an established hamster scrapie model to pursue a nove ... | 2007 | 18024919 |
| anti-prion activity generated by a novel vaccine formulation. | chronic wasting disease (cwd) is a transmissible spongiform encephalopathy (tse) of domestic and wild cervids in north america. to address possible prevention regimens for cwd, we have used a mouse model system and the rocky mountain laboratory (rml) mouse-adapted scrapie prion strain to screen efficacy of potential vaccine candidates. three peptides derived from the primary amino acid sequence of the prion protein were conjugated to blue carrier protein (bcp) and formulated in an adjuvant conta ... | 2007 | 18023980 |
| the role of parvalbumin and calbindin d28k in experimental scrapie. | prion diseases are generally characterized by pronounced neuronal loss. in particular, a subpopulation of inhibitory neurones, characterized by the expression of the calcium-binding protein parvalbumin (pv), is selectively destroyed early in the course of human and experimental prion diseases. by contrast, nerve cells expressing calbindin d28 k (cb), another calcium-binding protein, as well as pv/cb coexpressing purkinje cells, are well preserved. | 2008 | 18005331 |
| prp n-terminal domain triggers prp(sc)-like aggregation of dpl. | transmissible spongiform encephalopathies are fatal neurodegenerative disorders thought to be transmitted by self-perpetuating conformational conversion of a neuronal membrane glycoprotein (prp(c), for "cellular prion protein") into an abnormal state (prp(sc), for "scrapie prion protein"). doppel (dpl) is a protein that shares significant biochemical and structural homology with prp(c). in contrast to its homologue prp(c), dpl is unable to participate in prion disease progression or to achieve a ... | 2008 | 17997980 |
| cell division modulates prion accumulation in cultured cells. | the phenotypic effect of prions on host cells is influenced by the physical properties of the prion strain and its level of accumulation. in mammalian cell cultures, prion accumulation is determined by the interplay between de novo prion formation, catabolism, cell division, and horizontal cell-to-cell transmission. understanding this dynamic enables the analytical modeling of protein-based heritability and infectivity. here, we quantitatively measured these competing effects in a subline of neu ... | 2007 | 17989223 |
| [interaction between various prp segments and gfap in vitro]. | to study the potential interaction between prp protein and glial fibrillary acidic protein (gfap) and identify the binding region within prp with gfap. | 2007 | 17971924 |
| [establishment of a protein misfolding cyclic amplification for prpsc]. | to establish a methodology of protein misfolding cyclic amplification (pmca) and utilize in the detection of prp(sc) in brain tissues from prion diseases. | 2007 | 17971920 |
| sodium valproate does not augment prpsc in murine neuroblastoma cells. | sodium valproate (vpa) has been reported to increase the accumulation of the pathologic isoform of prion protein (prpsc) in scrapie-infected murine neuroblastoma cells. in this study, the effect of vpa on prpsc accumulation was investigated in murine n2a neuroblastoma cells chronically infected with scrapie strain 22l (n2a-22l). no accumulation of prpsc was detected after short-term (3 days) or long-term (21 days) treatment of n2a-22l cells with 4.8, 12, 18 or 24 microm vpa. higher vpa concentra ... | 2007 | 17967743 |
| prion protein alpha-to-beta transition monitored by time-resolved fourier transform infrared spectroscopy. | the conformational change of the recombinant, murine prion protein (prp) from an alpha-helical to a beta-sheet enriched state was monitored by time-resolved fourier transform infrared (ft-ir) spectroscopy. the alpha-to-beta transition is induced by reduction of the single disulfide bond in prp. this transition is believed to generate the scrapie form prp(sc), the supposed infectious agent of transmissible spongiform encephalopathies. we followed the kinetics of this conformational change using a ... | 2007 | 17958950 |
| direct detection of soil-bound prions. | scrapie and chronic wasting disease are contagious prion diseases affecting sheep and cervids, respectively. studies have indicated that horizontal transmission is important in sustaining these epidemics, and that environmental contamination plays an important role in this. in the perspective of detecting prions in soil samples from the field by more direct methods than animal-based bioassays, we have developed a novel immuno-based approach that visualises in situ the major component (prp(sc)) o ... | 2007 | 17957252 |
| disease-associated prion protein is not detectable in human systemic amyloid deposits. | cerebral and cardiac amyloid deposits have been reported after scrapie infection in transgenic mice expressing variant prion protein (prp(c)) lacking the glycophosphatidylinositol anchor. the amyloid fibril protein in the systemic amyloid deposits was not characterized, and there is no clinical or pathological association between prion diseases and systemic amyloidosis in humans. nevertheless, in view of the potential clinical significance of these murine observations, we tested both human amylo ... | 2007 | 17955450 |
| classic scrapie in sheep with the arr/arr prion genotype in germany and france. | in the past, natural scrapie and bovine spongiform encephalopathy (bse) infections have essentially not been diagnosed in sheep homozygous for the a136r154r171 haplotype of the prion protein. this genotype was therefore assumed to confer resistance to bse and classic scrapie under natural exposure conditions. hence, to exclude prions from the human food chain, massive breeding efforts have been undertaken in the european union to amplify this gene. we report the identification of 2 natural scrap ... | 2007 | 17953092 |
| differential expression of erythroid genes in prion disease. | we previously reported reduced expression of erythroid-associated factor (eraf) within haematopoietic tissues of rodent scrapie models, suggesting an unrecognized role for the erythroid lineage in prion disease. in the present study, we compared the expression of a panel of erythroid genes within four murine scrapie models and five virus infection models with parallels to prion disease pathogenesis. we report that differential expression of erythroid genes is not limited to eraf, and is a common ... | 2007 | 17950692 |
| differential expression and protein distribution of bax in natural scrapie. | bax is a pro-apoptotic member of the bcl-2 family that plays an important role in neuronal apoptosis. however, the results are controversial, especially regarding its function in the apoptosis involved in prion diseases. this work analyzes the gene expression and protein distribution of bax in the central nervous systems of sheep naturally infected with scrapie. gene expression profiling, obtained by means of real-time rt-pcr analysis, has shown a significant over-expression of this pro-apoptoti ... | 2007 | 17949698 |
| selective incorporation of polyanionic molecules into hamster prions. | the central pathogenic event of prion disease is the conformational conversion of a host protein, prpc, into a pathogenic isoform, prpsc. we previously showed that the protein misfolding cyclic amplification (pmca) technique can be used to form infectious prion molecules de novo from purified native prpc molecules in an autocatalytic process requiring accessory polyanions (deleault, n. r., harris, b. t., rees, j. r., and supattapone, s. (2007) proc. natl. acad. sci. u. s. a. 104, 9741-9746). her ... | 2007 | 17940287 |
| polymorphisms of the prnp gene in moroccan sheep breeds. | 2007 | 17938411 | |
| electron crystallography of the scrapie prion protein complexed with heavy metals. | the insolubility of the disease-causing isoform of the prion protein (prp(sc)) has prevented studies of its three-dimensional structure at atomic resolution. electron crystallography of two-dimensional crystals of n-terminally truncated prp(sc) (prp 27-30) and a miniprion (prp(sc)106) provided the first insights at intermediate resolution on the molecular architecture of the prion. here, we report on the structure of prp 27-30 and prp(sc)106 negatively stained with heavy metals. the interactions ... | 2007 | 17935686 |
| prion protein gene polymorphisms in four goat breeds of pakistan. | four different goat breeds (pak-angora, dera din panah, naachi and teddy) of pakistan were selected to investigate polymorphism in the prion protein gene (prp gene) responsible for scrapie disease resistance in goats. initially, genotyping of 187 animals of these four breeds by restriction fragment length polymorphism (rflp) was done to see the genotype for codon 136 and 154. all the animals were monomorphic with a genotype of aarr except one animal of teddy breed having the genotype of aarh. se ... | 2009 | 17934795 |
| the stability and aggregation of ovine prion protein associated with classical and atypical scrapie correlates with the ease of unwinding of helix-2. | susceptibility to scrapie disease in sheep, the archetypal prion disease, correlates with polymorphisms within the ovine prp (prion-related protein) gene. the vrq (val136arg154gln171) and al141rq (ala136leu141arg154gln171) allelic variants are associated with classical scrapie, whereas the arr (ala136arg154arg171), af141rq (ala136phe141arg154gln171) and ahq (ala136his154gln171) allelic variants are associated with atypical scrapie. recent studies have suggested that there are differences in the ... | 2008 | 17931166 |
| distribution of prion protein genotypes in breeds of sheep in new zealand. | to use an established high through-put genotyping procedure to gain an estimate of the frequency of alleles of the prion protein (prp) gene in some common sheep breeds in new zealand. | 2007 | 17928898 |
| assessment of prion inactivation by combined use of bacillus-derived protease and sds. | prions, infectious agents causing transmissible spongiform encephalopathy, retain infectivity even after undergoing routine sterilization processes. we found that msk103 protease, identified in our previous study, effectively reduces infectivity and the level of misfolded isoform of the prion protein in scrapie-infected brain homogenates in the presence of sds. the treatment therefore can be applied to the decontamination of thermolabile instruments. | 2007 | 17928684 |
| removal of the glycosylation of prion protein provokes apoptosis in sf126. | although the function of cellular prion protein (prpc) and the pathogenesis of prion diseases have been widely described, the mechanisms are not fully clarified. in this study, increases of the portion of non-glycosylated prion protein deposited in the hamster brains infected with scrapie strain 263k were described. to elucidate the pathological role of glycosylation profile of prp, wild type human prp (huprp) and two genetic engineering generated non-glycosylated prp mutants (n181q/n197q and t1 ... | 2007 | 17927898 |
| hemin interactions and alterations of the subcellular localization of prion protein. | hemin (iron protoporphyrin ix) is a crucial component of many physiological processes acting either as a prosthetic group or as an intracellular messenger. some unnatural, synthetic porphyrins have potent anti-scrapie activity and can interact with normal prion protein (prpc). these observations raised the possibility that hemin, as a natural porphyrin, is a physiological ligand for prpc. accordingly, we evaluated prpc interactions with hemin. when hemin (3-10 microm) was added to the medium of ... | 2007 | 17925394 |
| different structural stability and toxicity of prp(arr) and prp(arq) sheep prion protein variants. | the polymorphisms at amino acid residues 136, 154, and 171 in ovine prion protein (prp) have been associated with different susceptibility to scrapie: animals expressing prp(arq) [prp(ala136/arg154/gln171)] show vulnerability, whereas those that express prp(arr) [prp(ala136/arg154/arg171)] are resistant to scrapie. the aim of this study was to evaluate the in vitro toxic effects of prp(arr) and prp(arq) variants in relation with their structural characteristics. we show that both peptides cause ... | 2007 | 17919292 |
| associations between genotypes at codon 171 and 136 of the prion protein gene and production traits in market lambs. | to determine whether selection for the homozygous a136 r171 genotype that confers resistance to classic scrapie infection negatively affects production traits in sheep. | 2007 | 17916013 |
| prion strain- and species-dependent effects of antiprion molecules in primary neuronal cultures. | transmissible spongiform encephalopathies (tse) arise as a consequence of infection of the central nervous system by prions and are incurable. to date, most antiprion compounds identified by in vitro screening failed to exhibit therapeutic activity in animals, thus calling for new assays that could more accurately predict their in vivo potency. primary nerve cell cultures are routinely used to assess neurotoxicity of chemical compounds. here, we report that prion strains from different species c ... | 2007 | 17913812 |
| viruses as an etiology of obesity. | obesity is a serious chronic disease that has numerous etiologies. the prevalence of obesity has increased dramatically since about 1980 in the united states and worldwide in both developed and developing countries. this rapid spread is compatible with an infectious origin. this review discusses the 5 animal viruses and 3 human viruses that have been shown to cause obesity and examines the evidence to date for virus-induced obesity. the obesogenic animal viruses include canine distemper virus, r ... | 2007 | 17908526 |
| jak-stat signaling pathway mediates astrogliosis in brains of scrapie-infected mice. | scrapie is characterized histologically, in part, by astrogliosis in brain and spinal cord. however, the mechanisms of astrogliosis in brain injury occurring during prion infection are not well understood. in this study, we investigated the expression levels and cellular localization of janus kinase (jak) -signal transducers and activators of transcription (stat) signaling molecules and growth factors such as leukemia inhibitory factor (lif) and ciliary neurotropic factor (cntf) by western blot ... | 2007 | 17897356 |
| protective effect of prion protein via the n-terminal region in mediating a protective effect on paraquat-induced oxidative injury in neuronal cells. | transmissible spongiform encephalopathies are a group of neurodegenerative disorders caused by a posttranslational, conformational change in the cellular isoform of the prion protein (prp(c)) into an infectious, disease-associated form (prp(sc)). increasing evidence supports a role for prp(c) in the cellular response to oxidative stress. we investigated the effect of oxidative stress mediated by paraquat exposure on sh-sy5y neuroblastoma cells. a loss of mitochondrial membrane potential and subs ... | 2008 | 17896796 |
| atypical status of bovine spongiform encephalopathy in poland: a molecular typing study. | the aim of this study was to analyze molecular features of protease-resistant prion protein (prp(res)) in western blots of bse cases diagnosed in poland with respect to a possible atypical status. confirmed cases were analyzed by western blotting with several monoclonal antibodies directed at n-terminal and core epitopes of prion protein (prp). most cases showed the classical glycoprofile characterized by the dominance of the di- over the monoglycosylated prp(res) band, yielding di-/mono- ratios ... | 2008 | 17896076 |
| relevance of the regional lymph node in scrapie pathogenesis after peripheral infection of hamsters. | the exact role of the lymphoreticular system in the spread of peripheral prion infections to the central nervous system still needs further elucidation. against this background, the influence of the regional lymph node (ln. popliteus) on the pathogenesis of scrapie was monitored in a hamster model of prion infection via the footpad. | 2007 | 17894852 |
| prion removal by nanofiltration under different experimental conditions. | manufacturing processes used in the production of biopharmaceutical or biological products should be evaluated for their ability to remove potential contaminants, including tse agents. in the present study, we have evaluated scrapie prion protein (prp sc) removal in the presence of different starting materials, using virus removal filters of different pore sizes. following 75 nm filtration, prp sc was detected in the filtrate by western blot (wb) analysis when a "super-sonicated" microsomal frac ... | 2008 | 17890100 |
| [functions of prion protein prpc]. | it is now well established that both normal and pathological (or scrapie) isoforms of prion protein, prpc and prpsc respectively, are involved in the development and progression of various forms of neurodegenerative diseases, including scrapie in sheep, bovine spongiform encephalopathy (or "mad cow disease") and creutzfeldt-jakob disease in human, collectively known as prion diseases. the protein prpc is highly expressed in the central nervous system in neurons and glial cells, and also present ... | 2007 | 17875293 |
| mutant prion protein d202n associated with familial prion disease is retained in the endoplasmic reticulum and forms 'curly' intracellular aggregates. | transmissible spongiform encephalopathies are fatal neurodegenerative disorders of humans and animals that are familial, sporadic, and infectious in nature. familial disorders of humans include gerstmann-straussler-scheinker disease (gss), familial creutzfeldt-jakob disease (cjd), and fatal familial insomnia, and result from point mutations in the prion protein gene. although neurotoxicity in familial cases is believed to result from a spontaneous change in conformation of mutant prion protein ( ... | 2007 | 17873292 |
| scrapie in goats. | 2007 | 17873273 | |
| enteroglial and neuronal involvement without apparent neuron loss in ileal enteric nervous system plexuses from scrapie-affected sheep. | the enteric nervous system (ens) probably plays a dominant role in sheep scrapie pathogenesis, but little is known about the cell types involved. we investigated the ileal myenteric and submucosal plexuses of four naturally and four orally experimentally scrapie-affected arq/arq sarda sheep, as well as those of 12 healthy-control sarda sheep carrying different prp genotypes. all scrapie-affected animals, euthanized at clinical-disease end stage, showed prpd deposition within enteric glial cells ... | 2007 | 17872545 |
| urinary excretion and blood level of prions in scrapie-infected hamsters. | prions, infectious agents causing transmissible spongiform encephalopathy (tse), are composed primarily of the pathogenic form (prp(sc)) of the host-encoded prion protein. although very low levels of infectivity have been detected in urine from scrapie-infected rodents, no reports of urinary prp(sc) have been substantiated. studies on the dynamics of urinary prp(sc) during infection are needed to ensure the safety of urine-derived biopharmaceuticals and to assess the possible horizontal transmis ... | 2007 | 17872544 |
| the neurochemical nature of prp(c)-containing cells in the rat brain. | the cellular prion protein (prp(c)) is a membrane-bound glycoprotein abundantly expressed in neurons and glial cells within the cns. the scrapie prion protein (prp(sc)) is a conformationally altered isoform of prp(c) that is responsible for prion diseases, also termed transmissible spongiform encephalopathies (tse), a group of neurodegenerative diseases that affect a wide variety of mammal species, including humans. the presence of the cellular isoform of prp is necessary for the establishment a ... | 2007 | 17854776 |
| the tyrosine kinase inhibitor imatinib mesylate delays prion neuroinvasion by inhibiting prion propagation in the periphery. | prion diseases are fatal neurodegenerative disorders with no effective therapy. a hallmark of prion disease is the conversion of the normal cellular form of prion protein prp(c) into a disease-associated isoform prp(sc). the authors recently have shown that a tyrosine kinase inhibitor, imatinib mesylate, induces clearance of prp(sc) via specific inhibition of c-abl in prion-infected cell culture models. in this study, the authors assessed the in vivo effects of imatinib mesylate on prion disease ... | 2007 | 17849316 |
| intraepithelial and interstitial deposition of pathological prion protein in kidneys of scrapie-affected sheep. | prions have been documented in extra-neuronal and extra-lymphatic tissues of humans and various ruminants affected by transmissible spongiform encephalopathy (tse). the presence of prion infectivity detected in cervid and ovine blood tempted us to reason that kidney, the organ filtrating blood derived proteins, may accumulate disease associated prp(sc). we collected and screened kidneys of experimentally, naturally scrapie-affected and control sheep for renal deposition of prp(sc) from distinct, ... | 2007 | 17848990 |
| interaction between dendritic cells and nerve fibres in lymphoid organs after oral scrapie exposure. | in transmissible spongiform encephalopathies (tses), the infectious agent, called prpsc, an abnormal isoform of the cellular prion protein, accumulates and replicates in lymphoid organs before affecting the nervous system. to clarify the cellular requirements for the neuroinvasion of the scrapie agent from the lymphoid organs to the central nervous system, we have studied, by confocal microscopy, the innervations within peyer's patches, mesenteric lymph nodes and the spleen of mice in physiologi ... | 2007 | 17823814 |
| effectiveness of capillary electrophoresis fluoroimmunoassay of blood prpsc for evaluation of scrapie pathogenesis in sheep. | management of prion diseases in livestock would benefit greatly from availability of a validated blood test. a promising immunocapillary electrophoresis technique (also known as capillary electrophoresis fluoroimmunoassay) to detect abnormal prion protein in blood from live sheep is evaluated here. capillary electrophoresis fluoroimmunoassay was applied to analysis of extracted blood from scrapie-exposed sheep (n = 87; 347 samples) at various stages of incubation, and to control sheep (n = 194; ... | 2007 | 17823402 |
| detection of the disease-associated isoform of the prion protein in formalin-fixed tissues by western blot. | clinical signs of prion disease are not specific and include a variety of differential diagnoses. serological tests and nucleic acid-based detection methods are not applicable to prion-disease-agent detection because of the unusual nature of the infectious agent. prion-disease diagnosis is primarily conducted by means of immunodetection of the infectious agent, typically by at least 2 distinct procedures with immunohistochemistry and western blot being the most informative. these approaches diff ... | 2007 | 17823401 |
| nonpsychoactive cannabidiol prevents prion accumulation and protects neurons against prion toxicity. | prion diseases are transmissible neurodegenerative disorders characterized by the accumulation in the cns of the protease-resistant prion protein (prpres), a structurally misfolded isoform of its physiological counterpart prpsen. both neuropathogenesis and prion infectivity are related to prpres formation. here, we report that the nonpsychoactive cannabis constituent cannabidiol (cbd) inhibited prpres accumulation in both mouse and sheep scrapie-infected cells, whereas other structurally related ... | 2007 | 17804615 |
| spiroplasma spp. from transmissible spongiform encephalopathy brains or ticks induce spongiform encephalopathy in ruminants. | spiroplasma, small motile wall-less bacteria, are linked by molecular and serological studies to the transmissible spongiform encephalopathies (tses), which include scrapie in sheep, chronic wasting disease (cwd) in deer and creutzfeldt-jakob disease in humans. in this study, two experiments were undertaken to determine the role of spiroplasma in the pathogenesis of tse. in experiment 1, spiroplasma mirum, a rabbit tick isolate that had previously been shown to experimentally induce spongiform e ... | 2007 | 17761489 |
| mouse-adapted ovine scrapie prion strains are characterized by different conformers of prpsc. | the agent responsible for prion disease may exist in different forms, commonly referred to as strains, with each carrying the specific information that determines its own distinct biological properties, such as incubation period and lesion profile. biological strain typing of ovine scrapie isolates by serial passage in conventional mice has shown some diversity in ovine prion strains. however, this biological diversity remains poorly supported by biochemical prion strain typing. the protein-only ... | 2007 | 17728226 |
| experimental transmission of atypical scrapie to sheep. | active surveillance for transmissible spongiform encephalopathies in small ruminants has been an eu regulatory requirement since 2002. a number of european countries have subsequently reported cases of atypical scrapie, similar to previously published cases from norway, which have pathological and molecular features distinct from classical scrapie. most cases have occurred singly in flocks, associated with genotypes considered to be more resistant to classical disease. experimental transmissibil ... | 2007 | 17725818 |
| polymorphisms of the prion gene promoter region that influence classical bovine spongiform encephalopathy susceptibility are not applicable to other transmissible spongiform encephalopathies in cattle. | two regulatory region polymorphisms in the prion gene of cattle have been reported to have an association with resistance to classical bovine spongiform encephalopathy (bse). however, it is not known if this association also applies to other transmissible spongiform encephalopathies (tse) in cattle. in this report, we compare the relationship between these 2 polymorphisms and resistance in cattle affected with naturally occurring atypical bse as well as in cattle experimentally inoculated with e ... | 2007 | 17709775 |
| antiprion activity of cholesterol esterification modulators: a comparative study using ex vivo sheep fibroblasts and lymphocytes and mouse neuroblastoma cell lines. | our studies on the role of cholesterol homeostasis in the pathogenesis of scrapie revealed abnormal accumulation of cholesterol esters in ex vivo peripheral blood mononuclear cells (pbmcs) and skin fibroblasts from healthy and scrapie-affected sheep carrying a scrapie-susceptible genotype compared to sheep with a resistant genotype. similar alterations were observed in mouse neuroblastoma n2a cell lines persistently infected with mouse-adapted 22l and rml strains of scrapie that showed up to thr ... | 2007 | 17709472 |
| cyclic tetrapyrrole sulfonation, metals, and oligomerization in antiprion activity. | cyclic tetrapyrroles are among the most potent compounds with activity against transmissible spongiform encephalopathies (tses; or prion diseases). here the effects of differential sulfonation and metal binding to cyclic tetrapyrroles were investigated. their potencies in inhibiting disease-associated protease-resistant prion protein were compared in several types of tse-infected cell cultures. in addition, prophylactic antiscrapie activities were determined in scrapie-infected mice. the activit ... | 2007 | 17709470 |
| prion protein and the transmissible spongiform encephalopathies. | transmissible spongiform encephalopathies (tses) are fatal neurodegenerative diseases that occur in a wide variety of mammals. in humans, tse diseases include kuru, sporadic and iatrogenic creutzfeldt-jakob disease (cjd), gerstmann-sträussler-scheinker syndrome (gss), and fatal familial insomnia (ffi). so far, tse diseases occur only rarely in humans; however, scrapie is a widespread problem in sheep, and the recent epidemic of bovine spongiform encephalopathy (bse or mad cow disease) has seriou ... | 1997 | 17708907 |
| prion proteins: physiological functions and role in neurological disorders. | stanley prusiner was the first to promote the concept of misfolded proteins as a cause for neurological disease. it has since been shown by him and other investigators that the scrapie isoform of prion protein (prp(sc)) functions as an infectious agent in numerous human and non-human disorders of the central nervous system (cns). interestingly, other organ systems appear to be less affected, and do not appear to lead to major co-morbidities. the physiological function of the endogenous cellular ... | 2008 | 17707411 |
| cyclodextrins inhibit replication of scrapie prion protein in cell culture. | prion diseases are fatal neurodegenerative disorders that are caused by the conversion of a normal host-encoded protein, prp(c), to an abnormal, disease-causing form, prp(sc). this paper reports that cyclodextrins have the ability to reduce the pathogenic isoform of the prion protein prp(sc) to undetectable levels in scrapie-infected neuroblastoma cells. beta-cyclodextrin removed prp(sc) from the cells at a concentration of 500 microm following 2 weeks of treatment. structure activity studies re ... | 2007 | 17699584 |
| disease dynamics over very different time-scales: foot-and-mouth disease and scrapie on the network of livestock movements in the uk. | we analyse the relationship between the network of livestock movements in the uk and the dynamics of two diseases: foot-and-mouth disease (fmd), which has an incubation period of days, and scrapie, which incubates over years. for fmd, the time-scale of expected epidemics is similar to the time-scale of the evolution of the network. we argue that, under appropriate conditions, a static network analysis can be an appropriate tool for gaining insights into disease dynamics even when the relevant ti ... | 2007 | 17698478 |
| [establishment of the concept of prion diseases]. | the history of prion diseases is derived from descriptions of scrapie of sheep and goats in the eighteenth century. in 1920, creutzfeldt-jakob disease was reported as the first case of human prion diseases, which was recognized as subacute spongiform encephalopathy, one of neurodegenerative diseases. afterwards, many transmission experiments were performed, which lead to the establishment of the fundamental concept, transmissible spongiform encephalopathy(tse). the infectious agent was supposed ... | 2007 | 17695271 |
| [disease concept of the slow virus infection]. | this article gives a brief history of the terminology of slow virus infection, the conceptual change that occurred in it, the features common to slow infection and the current concept of slow virus infection. björn sigurdsson from the field of veterinary medicine proposed slow virus infection as unique mode of infection in 1954. its initial concept was remodeled along with the general acceptance of prion theory of sheep scrapie that was proposed in 1982. the features common to slow infection inc ... | 2007 | 17695269 |
| assessment of prion inactivation by fenton reaction using protein misfolding cyclic amplification and bioassay. | an abnormal isoform of the prion protein, associated with transmissible spongiform encephalopathies, retains infectivity even after undergoing routine sterilization processes. we found that a formulation of iron ions combined with hydrogen peroxide effectively reduced infectivity and the level of abnormal isoforms of the prion protein in scrapie-infected brain homogenates. therefore, the fenton reaction has potential for prion decontamination. | 2007 | 17690456 |
| analysis of multiple single nucleotide polymorphisms closely positioned in the ovine prnp gene using linear fluorescent probes and melting curve analysis. | resistance and susceptibility to scrapie has been associated with single nucleotide polymorphisms located within codons 136, 154 and 171 of the ovine prion protein gene (prnp). dual-labelled hybeacon probes were developed to analyse single and clustered polymorphisms within these and neighbouring codons. | 2007 | 17683552 |
| decrease in neuroinflammation after immunisation with synthetic prion peptides in an animal model of scrapie. | 2007 | 17682891 | |
| modeling of a propagation mechanism of infectious prion protein; a hexamer as the minimum infectious unit. | to construct a new model of the propagation mechanism of infectious scrapie-type prion protein (prp(sc)), here we conducted a disruption simulation of a prp(sc) nonamer using structure-based molecular dynamics simulation method based on a hypothetical prp(sc) model structure. the simulation results showed that the nonamer disrupted in cooperative manners into monomers via two significant intermediate states: (1) a nonamer with a partially unfolded surface trimer and (2) a hexamer and three monom ... | 2007 | 17678874 |
| treatment of scrapie pathogen 263k with tetracycline partially abolishes protease-resistant activity in vitro and reduces infectivity in vivo. | to study the possible effect of tetracycline on protease-resistant activity in vitro and infectivity in vivo of a scrapie strain 263k. | 2007 | 17672209 |
| copaxone interferes with the prp sc-gag interaction. | the hallmark of prion disease-induced neurodegeneration is the accumulation of prp(sc), a misfolded form of prp(c). in addition, several lines of evidence indicate a role for the immune system and, in particular, inflammation in prion disease pathogenesis. in this work, we tested whether copaxone, an immunomodulatory agent currently used for the treatment of multiple sclerosis, can affect prion disease manifestation in scrapie-infected hamsters. we show here that copaxone exerted no effect on pr ... | 2007 | 17662008 |
| prion proteins: a biological role beyond prion diseases. | the biological role of the scrapie isoform of prion protein (prp(sc)) as an infectious agent in numerous human and non-human disorders of the central nervous system is well established. in contrast, and despite decades of intensive research, the physiological function of the endogenous cellular form of the prion protein (prp(c)) remains elusive. in mammals, the ubiquitous expression of prp(c) suggests biological functions other than its pathological role in propagating the accumulation of its mi ... | 2007 | 17661791 |
| a novel real-time ultrasonic method for prion protein detection using plasminogen as a capture molecule. | high resolution ultrasonography (hr-us) can monitor the molecular changes and biochemical interactions between proteins in real-time. the aim of this study was to use hr-us to characterize the real-time interactions between plasminogen coated beads and prpsc and to determine if this approach could be applied to the identification of animals affected by prion diseases. plasminogen, immobilized to beads, was used as a capturing tool for prpsc in brain homogenates from scrapie affected sheep and th ... | 2007 | 17659071 |
| mechanistic insights into the cure of prion disease by novel antiprion compounds. | prion diseases are fatal neurodegenerative disorders. identification of possible therapeutic tools is important in the search for a potential treatment for these diseases. congo red is an azo dye that has been used for many years to detect abnormal prion protein in the brains of diseased patients or animals. congo red has little therapeutic potential for the treatment of these diseases due to toxicity and poor permeation of the blood-brain barrier. we have prepared two congo red derivatives, des ... | 2007 | 17652397 |
| prion protein expression differences in microglia and astroglia influence scrapie-induced neurodegeneration in the retina and brain of transgenic mice. | activated microglia and astroglia are known to be involved in a variety of neurodegenerative diseases, including prion diseases. in the present experiments, we studied activation of astroglia and microglia after intraocular scrapie infection in transgenic mice expressing prion protein (prp) in multiple cell types (tg7 mice) or in neurons only (tgnse mice). in this model, scrapie infection and protease-resistant prp deposition occurs in the retinas of both strains of mice, but retinal degeneratio ... | 2007 | 17652390 |
| molecular profiling of ovine prion diseases by using thermolysin-resistant prpsc and endogenous c2 prp fragments. | disease-associated prp fragments produced upon in vitro or in vivo proteolysis can provide significant insight into the causal strain of prion disease. here we describe a novel molecular strain typing assay that used thermolysin digestion of caudal medulla samples to produce prpres signatures on western blots that readily distinguished experimental sheep bovine spongiform encephalopathy (bse) from classical scrapie. furthermore, the accumulation of such prpres species within the cerebellum also ... | 2007 | 17652380 |
| testing the equivalence of different ovine prp genotypes for estimated breeding values. | in this study we applied equivalence testing methods to prove the absence of differences in genetic values of ewes with different prp genotypes. in particular, the milk production genetic value equivalence of arr ovine prion protein (prp) genotypes was analysed. there is no scientific evidence implying that the performances and genetic values of different prp genotypes will be different, but it is interesting to confirm that the performance of one genotype is indistinguishable from another befor ... | 2007 | 17651323 |
| scrapie i. transmission and pathogenesis. | homogenized brain, extracts, and residues of brain from normal and scrapie sheep were inoculated into 116 sheep. of 72 sheep inoculated with scrapie material 27 developed the disease, whereas four of 44 inoculated with ;normal' brain material showed symptoms similar to those of scrapie. the scrapie agent survived extraction for 18 hours with diethyl ether followed by water for 24 hours. similarly the agent survived extraction in a soxhlet apparatus with 95 per cent ethanol containing 2.0 per cen ... | 1963 | 17649434 |
| a note on serum proteins in normal and scrapie infected sheep. | 1960 | 17649244 | |
| potassium and hemoglobin types in sheep with special reference to the transmission of scrapie. | 1960 | 17649201 | |
| scrapie-a disease of sheep: a review of the literature. | 1946 | 17648176 | |
| ultrasensitive detection of scrapie prion protein using seeded conversion of recombinant prion protein. | the scrapie prion protein isoform, prpsc, is a prion-associated marker that seeds the conformational conversion and polymerization of normal protease-sensitive prion protein (prp-sen). this seeding activity allows ultrasensitive detection of prpsc using cyclical sonicated amplification (pmca) reactions and brain homogenate as a source of prp-sen. here we describe a much faster seeded polymerization method (rprp-pmca) which detects >or=50 ag of hamster prpsc (approximately 0.003 lethal dose) with ... | 2007 | 17643109 |
| investigations of a prion infectivity assay to evaluate methods of decontamination. | prions are unique infectious agents which have been shown to be transmitted iatrogenically through contaminated surfaces. surface contamination is a concern on reusable medical devices and various industrial surfaces, but there is currently no standard, accepted model to evaluate surface prion decontamination. in this report, a set of both in vitro and in vivo methods were investigated based on the contamination of surface through artificial exposure to infected brain. an in vitro surface contam ... | 2007 | 17640752 |
| cellular prion protein (prpc) protects neuronal cells from the effect of huntingtin aggregation. | the effect of normal cellular prion protein (prp(c)) on abnormal protein aggregation was examined by transfecting huntingtin fragments (htt) into sn56 neuronal-derived cells depleted of prp(c) by rna interference. prp(c) depletion caused an increase in both the number of cells containing granules and the number of apoptotic cells. consistent with the increase in htt aggregation, prp(c) depletion caused an decrease in proteasome activity and a decrease in the activities of cellular defense enzyme ... | 2007 | 17635996 |
| is vaccination against transmissible spongiform encephalopathy feasible? | prion diseases are a unique category of illness, affecting both animals and humans, where the underlying pathogenesis is related to a conformation change of the cellular form of a normal, self-protein called a prion protein (prp(c) [c for cellular]) to a pathological and infectious conformation known as scrapie form (prpsc [sc for scrapie]). currently, all prion diseases are without effective treatment and are universally fatal. the emergence of bovine spongiform encephalopathy and variant creut ... | 2007 | 17633306 |
| prpc does not mediate internalization of prpsc but is required at an early stage for de novo prion infection of rov cells. | we have studied the interactions of exogenous prions with an epithelial cell line inducibly expressing prpc protein and permissive to infection by a sheep scrapie agent. we demonstrate that abnormal prp (prpsc) and prion infectivity are efficiently internalized in rov cells, whether or not prpc is expressed. at odds with earlier studies implicating cellular heparan sulfates in prpsc internalization, we failed to find any involvement of such molecules in rov cells, indicating that prions can ente ... | 2007 | 17626095 |
| fatal neurological disease in scrapie-infected mice induced for experimental autoimmune encephalomyelitis. | during the years or decades of prion disease incubation, at-risk individuals are certain to encounter diverse pathological insults, such as viral and bacterial infections, autoimmune diseases, or inflammatory processes. whether prion disease incubation time and clinical signs or otherwise the pathology of intercurrent diseases can be affected by the coinfection process is unknown. to investigate this possibility, mice infected with the scrapie agent at both high and low titers were subsequently ... | 2007 | 17626090 |
| experimental scrapie in 'plt' mice: an assessment of the role of dendritic-cell migration in the pathogenesis of prion diseases. | peripherally acquired transmissible spongiform encephalopathies display strikingly long incubation periods, during which increasing amounts of prions can be detected in lymphoid tissues. while precise sites of peripheral accumulation have been described, the mechanisms of prion transport from mucosa and skin to lymphoid and nervous tissues remain unknown. because of unique functional abilities, dendritic cells (dcs) have been suspected to participate in prion pathogenesis. in mice inoculated sub ... | 2007 | 17622642 |
| oral scrapie infection modifies the homeostasis of peyer's patches' dendritic cells. | in transmitted prion diseases the immune system supports the replication and the propagation of the pathogenic agent (prpsc). dcs, which are mobile cells present in large numbers within lymph organs, are suspected to carry prions through the lymphoid system and to transfer them towards the peripheral nervous system. in this study, c57bl/6 mice were orally inoculated with prpsc (scrapie strain 139a) and sacrificed at the preclinical stages of the disease. immunolabelled cryosections of peyer's pa ... | 2007 | 17622551 |
| immunohistochemistry for prpsc in natural scrapie reveals patterns which are associated with the prp genotype. | immunohistochemistry for prpsc is used widely in scrapie diagnosis. in natural scrapie cases the use of immunohistochemistry (ihc) has revealed the existence of up to 12 different morphological types of immunostained deposits. the significance of this pattern variability in relation to genotype has not been studied extensively in natural disease. in this study we recorded in detail prpsc patterns at the obex level of the medulla oblongata from 163 animals derived from 55 flocks which presented t ... | 2007 | 17617872 |
| disease-specific particles without prion protein in prion diseases - phenomenon or epiphenomenon? | the search for the cause of transmissible spongiform encephalopathies (tses) has a long and tortuous history. in a recent paper, 25-nm virus-like particles were identified that were consistently observed in cell cultures infected with creutzfeldt-jakob disease (cjd) and scrapie; they are similar to, or even identical with, the virus-like tubulovesicular structures (tvs) found in experimental scrapie as early as in 1968, and subsequently in all naturally occurring and experimentally induced tses. ... | 2007 | 17617871 |
| classical sheep transmissible spongiform encephalopathies: pathogenesis, pathological phenotypes and clinical disease. | scrapie is a prion disease or transmissible spongiform encephalopathy (tse) of sheep, goats and moufflon. as with its human counterparts, pathology consists of vacuolation, gliosis and accumulations of abnormal forms of a host prion protein (prpd) in the brain of affected individuals. immunohistochemical methods can be used to identify both the intracellular truncation sites of prpd in different cell types (prpd epitope mapping) and the different morphological patterns of accumulation (prpd prof ... | 2007 | 17617870 |
| hot spots in prion protein for pathogenic conversion. | prion proteins are key molecules in transmissible spongiform encephalopathies (tses), but the precise mechanism of the conversion from the cellular form (prp(c)) to the scrapie form (prp(sc)) is still unknown. here we discovered a chemical chaperone to stabilize the prp(c) conformation and identified the hot spots to stop the pathogenic conversion. we conducted in silico screening to find compounds that fitted into a "pocket" created by residues undergoing the conformational rearrangements betwe ... | 2007 | 17616582 |
| alteration of iron regulatory proteins (irp1 and irp2) and ferritin in the brains of scrapie-infected mice. | considerable evidence suggests that oxidative stress may be involved in the pathogenesis of transmissible spongiform encephalopathies (tses). to investigate the involvement of iron metabolism in tses, we examined the expression levels of iron regulatory proteins (irps), ferritins, and binding activities of irps to iron-responsive element (ire) in scrapie-infected mice. we found that the irps-ire-binding activities and ferritins were increased in the astrocytes of hippocampus and cerebral cortex ... | 2007 | 17614197 |
| discrimination of sheep susceptible and resistant to transmissible spongiform encephalopathies by an haplotype specific monoclonal antibody. | in the present report, the selective detection of sheep prp haplotypes by monoclonal antibody 2a11 is described. it is showed that the substitution of glutamine by arginine but not by histidine at ovine prp position 171 abolishes completely the recognition of either prp(c) or prp(d) by mab 2a11, in such a way that the application of this antibody allows the unambiguous discrimination of r(171) homozygotes. on the basis of the high resistance to classical scrapie and bovine spongiform encephaloph ... | 2007 | 17614145 |
| susceptibility of cattle to first-passage intracerebral inoculation with chronic wasting disease agent from white-tailed deer. | fourteen, 3-month-old calves were intracerebrally inoculated with the agent of chronic wasting disease (cwd) from white-tailed deer (cwdwtd) to compare the clinical signs and neuropathologic findings with those of certain other transmissible spongiform encephalopathies (tse, prion diseases) that have been shown to be experimentally transmissible to cattle (sheep scrapie, cwd of mule deer [cwdmd], bovine spongiform encephalopathy [bse], and transmissible mink encephalopathy). two uninoculated cal ... | 2007 | 17606510 |
| expression of the prion protein gene (prnp) and cellular prion protein (prpc) in cattle and sheep fetuses and maternal tissues during pregnancy. | we investigated the expression of prion protein gene both on mrna and protein levels in bovine and ovine female reproductive organs during gestation and various tissues of their fetuses. the fetal tissues of both species included brain, cotyledon, heart, intestine, kidney, liver, lung, and muscle. in cattle, prion protein gene (prnp) transcripts were detected by semiquantitative rt-pcr in reproductive tissues such as ovary, oviduct, endometrium, myometrium, follicles, and granulosa cells. in var ... | 2007 | 17605301 |
| explaining the heterogeneous scrapie surveillance figures across europe: a meta-regression approach. | two annual surveys, the abattoir and the fallen stock, monitor the presence of scrapie across europe. a simple comparison between the prevalence estimates in different countries reveals that, in 2003, the abattoir survey appears to detect more scrapie in some countries. this is contrary to evidence suggesting the greater ability of the fallen stock survey to detect the disease. we applied meta-analysis techniques to study this apparent heterogeneity in the behaviour of the surveys across europe. ... | 2007 | 17598881 |
| canadian association of neurosciences review: prion protein and prion diseases: the good and the bad. | in the 1700's a strange new disease affecting sheep was recognized in europe. the disease later became known as "scrapie" and was the first of a family of similar diseases affecting a number of species that are now known as the transmissible spongiform encephalopathies (tses). the appearance of a new disease in humans linked to the consumption of meat products from infected cattle has stimulated widespread public concern and scientific interest in the prion protein and related diseases. nearly 3 ... | 2007 | 17598589 |
| simultaneous detection of eight single nucleotide polymorphisms in the ovine prion protein gene. | amino acid polymorphisms in the prion protein gene (prp) affect the susceptibility of sheep to scrapie, a transmissible spongiform encephalopathy (tse). in particular, amino acid substitutions at codons 136, 154 and 171 of the ovine prp gene are associated with different degrees of susceptibility to the classical form of scrapie, caused by 'typical' scrapie strains. existing genotyping tests for scrapie susceptibility normally interrogate only the single nucleotide polymorphisms (snps) most rele ... | 2007 | 17590312 |
| the importance of the prp genotype in active surveillance for ovine scrapie. | surveillance activities for ovine scrapie have expanded in the 21st century, following concerns about the potential for a hidden epidemic of bovine spongiform encephalopathy in european sheep populations. large-scale surveys have been used to estimate the prevalence of scrapie infection. in this study we analyse data from the surveys in great britain between 2002 and 2004. when we estimate genotype-specific prevalences for each of the two screening tests used a difference is observed. one test u ... | 2008 | 17588284 |
| insights into prion strains and neurotoxicity. | transmissible spongiform encephalopathies (tses) are neurodegenerative diseases that are caused by prions and affect humans and many animal species. it is now widely accepted that the infectious agent that causes tses is prp(sc), an aggregated moiety of the host-derived membrane glycolipoprotein prp(c). although prp(c) is encoded by the host genome, prions themselves encipher many phenotypic tse variants, known as prion strains. prion strains are tse isolates that, after inoculation into distinc ... | 2007 | 17585315 |
| exposure of sheep scrapie brain homogenate to rumen-simulating conditions does not result in a reduction of prp(sc) levels. | experiments were designed to evaluate the potential of rumen-simulating conditions to reduce prp(sc) levels. | 2007 | 17576225 |
| single chain fv antibodies directed against the 37 kda/67 kda laminin receptor as therapeutic tools in prion diseases. | transmissible spongiform encephalopathies are a group of neurological disorders associated with the deposition of prp(sc), an abnormal form of the cellular prion protein prp(c). the 37 kda/67 kda laminin receptor (lrp/lr) has been identified as a prion receptor and several lines of evidence strongly suggest that this protein plays a role during prion pathogenesis. here we report the selection of recombinant single chain antibodies (scfvs) directed against lrp from naïve and synthetic phage scfv ... | 2008 | 17576014 |
| lack of prp(sc) immunostaining in intracranial ectopic lymphoid follicles in a sheep with concomitant non-suppurative encephalitis and nor98-like atypical scrapie: a case report. | during active surveillance for transmissible spongiform encephalopathies (tses) in sheep, an initial reactor was detected using a rapid test on a brain sample. immunohistochemistry confirmed an atypical tse presentation that closely resembled the previously described nor98 cases. sequencing of the prnp gene confirmed the arq/ahq genotype with the l141f mutation at codon 141 associated with this phenotype. the head, including the brain and cranial lymphoid tissues, was sampled and examined thorou ... | 2008 | 17574883 |