Publications

histopathological studies of "ch1641-like" scrapie sources versus classical scrapie and bse transmitted to ovine transgenic mice (tgovprp4).	the possibility of the agent causing bovine spongiform encephalopathy (bse) infecting small ruminants is of serious concern for human health. among scrapie cases, the ch1641 source in particular appears to have certain biochemical properties similar to the bse strain. in france, several natural scrapie cases were identified as "ch1641-like" natural scrapie isolates in sheep and goats. the tg(ovprp4) mouse line expressing the ovine prion protein is a sensitive model for studying and identifying s ...	2011	21765939
amyloid: little proteins, big clues.		2011	21760575
from high-throughput cell culture screening to mouse model: identification of new inhibitor classes against prion disease.	transmissible spongiform encephalopathies (tse) or prion diseases belong to a category of fatal and so far untreatable neurodegenerative conditions. all prion diseases are characterized by both degeneration in the central nervous system (cns) in humans and animals and the deposition and accumulation of proteinase k-resistant prion protein (prp(res) ). until now, no pharmaceutical product has been available to cure these diseases or to alleviate their associated symptoms. here, a cell-culture scr ...	2011	21755599
characterization of the prnp gene locus in chios dairy sheep and its association with milk production and reproduction traits.	the objective of this study was to examine the prion protein gene locus (prnp) in chios sheep. prnp is linked with scrapie resistance in small ruminants. here, its impact on milk production (test-day and total lactation yield) and reproduction (age at first lambing, conception rate at first service, and prolificacy) was assessed. genotyping at codons 136, 154 and 171 (classical scrapie) and 141 (atypical scrapie) was performed using dna from milk somatic cells and pcr-rflp analysis. a total of 1 ...	2011	21749423
steric zipper formed by hydrophobic peptide fragment of syrian hamster prion protein.	steric zippers, where the residues of two neighboring ß-sheet layers are tightly interdigitated, have been proposed as fundamental structural units of amyloid fibrils by eisenberg and co-workers. the steric zipper formed by polypeptides containing the palindromic sequence agaaaaga has a distinctive feature that the distance between two interdigitated ß-sheet layers is comparable to the interstrand distance of the individual ß-sheet. this structural motif is of great interest in the study of prio ...	2011	21749158
diphenyl-pyrazole derived compounds increase survival time of mice after prion infection.	transmissible spongiform encephalopathies (tses) represent a group of fatal neurodegenerative disorders which can be transmitted by natural infection or inoculation. tses include scrapie in sheep, bse in cattle, and creutzfeldt-jakob disease (cjd) in humans. the emergence of a variant form of cjd (vcjd) which has been associated to bse, produced strong pressure to search for effective treatments with new drugs. up to now, however, tses are incurable, although many efforts have been made in vitro ...	2011	21746938
analysis of nucleic acid chaperoning by the prion protein and its inhibition by oligonucleotides.	prion diseases are unique neurodegenerative illnesses associated with the conversion of the cellular prion protein (prp(c)) into the aggregated misfolded scrapie isoform, named prp(sc). recent studies on the physiological role of prp(c) revealed that this protein has probably multiple functions, notably in cell-cell adhesion and signal transduction, and in assisting nucleic acid folding. in fact, in vitro findings indicated that the human prp (huprp) possesses nucleic acid binding and annealing ...	2011	21737432
conserved properties of human and bovine prion strains on transmission to guinea pigs.	the first transmissions of human prion diseases to rodents used guinea pigs (gps, cavia porcellus). later, transgenic mice expressing human or chimeric human/mouse prp replaced gps, but the small size of the mouse limits some investigations. to investigate the fidelity of strain-specific prion transmission to gps, we inoculated 'type 1' and 'type 2' prion strains into gps, and we measured the incubation times and determined the strain-specified size of the unglycosylated, protease-resistant (r) ...	2011	21727894
Molecular cloning and polymorphism analysis of the prion protein gene in Tan sheep of Ningxia, China.	The resistance or susceptibility of sheep to scrapie is associated with polymorphisms of the prion protein gene (PRNP), particularly, single nucleotide polymorphisms (SNPs) in amino acid positions 136, 154 and 171. The prion protein (PrP) gene sequence and the deduced amino acid alignment of prion protein in Tan sheep, a local Chinese sheep breed traditionally raised in Ningxia, northwestern China, were determined and variability of the PrP amino acids sequence was analyzed in this study. The Pr ...	2011	21722718
enhancement of immunohistochemical staining of scrapie proteins and immune cells within lymph nodes of early scrapie-infected sheep.	transmissible spongiform encephalopathies (tse) are a group of fatal neurodegenerative diseases that affect animals as well as humans. the oldest of these diseases is scrapie seen in sheep. scrapie is caused by an altered form (prp(sc)), capable of inducing "self-replication" of the normal host prion protein(prp(c)). there is currently no universal standard for antigen retrieval when using immunohistochemistry to simultaneously stain the prp(c) protein and other cellular markers. the use of form ...	2011	21722647
prion disease detection, pmca kinetics, and igg in urine from sheep naturally/experimentally infected with scrapie and deer with preclinical/clinical chronic wasting disease.	prion diseases, also known as transmissible spongiform encephalopathies, are fatal neurodegenerative disorders. low levels of infectious agent and limited, infrequent success of disease transmissibility and prp(sc) detection have been reported with urine from experimentally infected clinical cervids and rodents. we report the detection of prion disease-associated seeding activity (pasa) in urine from naturally and orally infected sheep with clinical scrapie agent and orally infected preclinical ...	2011	21715495
survival of infectious prions in water.	the objective of this study was to evaluate the fate of infectious prions in water. known concentrations of infectious prions were added to deionized water, tap water, and wastewater. samples were incubated at 25-¦c, 37-¦c, and 50-¦c for 1 to 8 weeks. the standard scrapie cell assay (ssca) which includes the elispot (enzyme linked immuno-spot) reaction was performed to determine prion infectivity and quantity as a function of time. a reduction of infectious prions was observed at 25-¦c, 37-¦c, a ...	2011	21707419
Bee venom phospholipase A2 prevents prion peptide induced-cell death in neuronal cells.	Bee venom phospholipase A2 (bvPLA2) is a prototypic group-áIII enzyme which consists of unique N-terminal and C-terminal domains and a central secretory PLA2 (sPLA2) domain. This sPLA2 domain is highly homologous with human group-áIII sPLA2. Current evidence suggests that group-áIII sPLA2 may affect some neuronal functions, such as neuritogenesis, neurotransmitter release and neuronal survival. The prion diseases are neurodegenerative disorders characterized by the conversion of the normal cellu ...	2011	21701769
common structural traits across pathogenic mutants of the human prion protein and their implications for familial prion diseases.	human (hu) familial prion diseases are associated with about 40 point mutations of the gene coding for the prion protein (prp). most of the variants associated with these mutations are located in the globular domain of the protein. we performed 50-áns of molecular dynamics for each of these mutants to investigate their structure in aqueous solution. overall, 1.6-á++s of molecular dynamics data is presented. the calculations are based on the amber(parm99) force field, which has been shown to repr ...	2011	21689662
transcriptional profiling of peripheral lymphoid tissue reveals genes and networks linked to ssbp/1 scrapie pathology in sheep.	transmissible spongiform encephalopathies (tses) are slow and progressive neurodegenerative diseases of humans and animals. the major target organ for all tses is the brain but some tse agents are associated with prior accumulation within the peripheral lymphoid system. many studies have examined the effects of scrapie infection on the expression of central nervous system (cns) genes, but this study examines the progression of scrapie pathology in the peripheral lymphoid system and how scrapie i ...	2011	21684093
assessment of the genetic susceptibility of sheep to scrapie by protein misfolding cyclic amplification and comparison with experimental scrapie transmission studies.	the susceptibility of sheep to scrapie is influenced mainly by the prion protein polymorphisms a136v, r154h, and q171r/h. here we analyzed the ability of protein misfolding cyclic amplification (pmca) to model the genetic susceptibility of sheep to scrapie. for this purpose, we studied the efficiency of brain homogenates from sheep with different prp genotypes to support prp(sc) amplification by pmca using an arq/arq scrapie inoculum. the results were then compared with those obtained in vivo us ...	2011	21680531
mutation directional selection sheds light on prion pathogenesis.	as mutations in the prnp gene account for human hereditary prion diseases (prds), it is crucial to elucidating how these mutations affect the central pathogenic conformational transition of normal cellular prion protein (prp(c)) to abnormal scrapie isoform (prp(sc)). many studies proposed that these pathogenic mutations may make prp more susceptible to conformational change through altering its structure stability. by evaluating the most recent observations regarding pathogenic mutations, it was ...	2011	21679685
characterization of prnp and sprn coding regions from atypical scrapie cases diagnosed in poland.	scrapie, a fatal transmissible spongiform encephalopathy (tse) occurs in two phenotypes: classical and atypical. many authors point out that the polymorphism of three codons (136, 154, 171) of the prnp (prp gene) is associated with a sheep susceptibility to classical scrapie. until now, only one prnp gene variant coding phenylalanine at codon 141 has been found to be associated with atypical scrapie. another recently identified and interesting candidate gene for scrapie susceptibility in sheep i ...	2011	21674189
uptake dynamics of scrapie agent in the intestinal villous epithelium of suckling and weanling syrian hamsters.	in mice, the number of intestinal villous columnar epithelium cells that incorporate abnormal prion protein (prp(sc) ) decreases significantly after weaning. in this study, to investigate the dynamics of prp(sc) uptake during the growth of hamsters, scrapie 263k agent was inoculated orally into suckling and weanling syrian hamsters and the number of prp(sc) -positive villous epithelium cells was estimated immunohistochemically. the number of prp(sc) -positive cells declined significantly as the ...	2011	21668484
quantitative detection and biological propagation of scrapie seeding activity in vitro facilitate use of prions as model pathogens for disinfection.	prions are pathogens with an unusually high tolerance to inactivation and constitute a complex challenge to the re-processing of surgical instruments. on the other hand, however, they provide an informative paradigm which has been exploited successfully for the development of novel broad-range disinfectants simultaneously active also against bacteria, viruses and fungi. here we report on the development of a methodological platform that further facilitates the use of scrapie prions as model path ...	2011	21647368
photodegradation illuminates the role of polyanions in prion infectivity.	understanding the mechanism by which prion infectivity is encoded by the misfolded protein prp (sc ) remains a high priority within the prion field. work from several groups has indicated cellular cofactors may be necessary to form infectious prions in vitro. the identity of endogenous prion conversion cofactors is currently unknown, but may include polyanions and/or lipid molecules. in a recent study, we manufactured infectious hamster prions containing purified prp (sc) , co-purified lipid, an ...	2011	21646861
mechanism of prp-amyloid formation in mice without transmissible spongiform encephalopathy.	gerstmann-sträussler-scheinker (gss) p102l disease is a familial form of a transmissible spongiform encephalopathy (tse) that can present with or without vacuolation of neuropil. inefficient disease transmission into 101ll transgenic mice was previously observed from gss p102l without vacuolation. however several aged, healthy mice had large plaques composed of abnormal prion protein (prp(d) ). here we perform the ultrastructural characterisation of such plaques and compare them with prp(d ) agg ...	2011	21645162
estimation of variant creutzfeldt-jakob disease infectivity titers in human blood.	background: blood of individuals with variant creutzfeldt-jakob disease (vcjd) is infectious but the titer is unknown. current estimates of possible vcjd infectivity titers in blood have largely relied on an assumption that the titers of vcjd agent in human blood are likely to be similar to those in blood of rodents infected with model transmissible spongiform encephalopathy agents, assayed by intracerebral inoculations of rodents of the same species. study design and methods: we analyzed publis ...	2011	21645006
clinical, electroretinographic and histomorphometric evaluation of the retina in sheep with natural scrapie.	abstract: background: the retina is part of the diencephalon in a peripheral location and may be involved in prion diseases. retinal function and structural changes were assessed in naturally scrapie-affected red face manech ewes presenting the classical signs of the disease, and clinically healthy age-matched subjects for controls. ophthalmic examination was done prior to electroretinography (erg), which was carried out under conditions that allowed photopic and scotopic activities to be assess ...	2011	21639947
gene expression profiling and association with prion-related lesions in the medulla oblongata of symptomatic natural scrapie animals.	the pathogenesis of natural scrapie and other prion diseases remains unclear. examining transcriptome variations in infected versus control animals may highlight new genes potentially involved in some of the molecular mechanisms of prion-induced pathology. the aim of this work was to identify disease-associated alterations in the gene expression profiles of the caudal medulla oblongata (mo) in sheep presenting the symptomatic phase of natural scrapie. the gene expression patterns in the mo from ...	2011	21629698
lack of a-disintegrin-and-metalloproteinase adam10 leads to intracellular accumulation and loss of shedding of the cellular prion protein in vivo.	abstract: background: the cellular prion protein (prpc) fulfils several yet not completely understood physiological functions. apart from these functions, it has the ability to misfold into a pathogenic scrapie form (prpsc) leading to fatal transmissible spongiform encephalopathies. proteolytic processing of prpc generates n- and c-terminal fragments which play crucial roles both in the pathophysiology of prion diseases and in transducing physiological functions of prpc. a-disintegrin-and-metall ...	2011	21619641
atypical prion diseases in humans and animals.	although prion diseases, such as creutzfeldt-jakob disease (cjd) in humans and scrapie in sheep, have long been recognized, our understanding of their epidemiology and pathogenesis is still in its early stages. progress is hampered by the lengthy incubation periods and the lack of effective ways of monitoring and characterizing these agents. protease-resistant conformers of the prion protein (prp), known as the "scrapie form" (prp(sc)), are used as disease markers, and for taxonomic purposes, in ...	2011	21598097
detection of four novel polymorphisms in prp gene of pakistani sheep (damani and hashtnagri) and goats (kamori and local hairy) breeds.	abstract: scrapie is a fatal neurodegenerative disorder of sheep and goats caused by post-translational conformational change in the host-encoded prion protein (prpc). susceptibility or resistance to scrapie has been associated with the presence of polymorphisms in the prion protein (prp) gene. in the present study, we analyzed the prp gene sequence to determine the frequency of polymorphisms in 56 sheep (28 each from damani and hashtnagri breeds) and 56 goats (28 each from kamori and local hair ...	2011	21595993
detection of prions in the faeces of sheep naturally infected with classical scrapie.	abstract: classical scrapie is a naturally transmitted prion disease of sheep and goats. contaminated environments may contribute to the spread of disease and evidence from animal models has implicated urine, blood, saliva, placenta and faeces as possible sources of the infection. here we sought to determine whether sheep naturally infected with classical scrapie shed prions in their faeces. we used serial protein misfolding cyclic amplification (spmca) along with two extraction methods to exami ...	2011	21592355
detection and localisation of prp in the liver of sheep infected with scrapie and bovine spongiform encephalopathy.	prions are largely contained within the nervous and lymphoid tissue of transmissible spongiform encephalopathy (tse) infected animals. however, following advances in diagnostic sensitivity, prp(sc), a marker for prion disease, can now be located in a wide range of viscera and body fluids including muscle, saliva, blood, urine and milk, raising concerns that exposure to these materials could contribute to the spread of disease in humans and animals. previously we demonstrated low levels of infect ...	2011	21589864
an enzymatic treatment of soil-bound prions effectively inhibits replication.	chronic wasting disease (cwd) and scrapie can be transmitted through indirect environmental routes, possibly via soil, and a practical decontamination strategy for prion-contaminated soil is currently unavailable. in the laboratory, an enzymatic treatment under environmentally-relevant conditions (22°c, ph 7.4) can degrade soil-bound prp(sc) below the limits of western blot detection. we developed and used a quantitative serial protein misfolding cyclic amplification (pmca) protocol to character ...	2011	21571886
heparin enhances the cell-protein misfolding cyclic amplification efficiency of variant creutzfeldt-jakob disease.	highly sensitive in vitro screening tests are required to prevent the iatrogenic spread of variant creutzfeldt-jakob disease (vcjd). protein misfolding cyclic amplification (pmca) is a candidate for such a test, but the sensitivity of this method is insufficient. polyanions were reported to enhance pmca efficiency, but their effects on vcjd are unclear. we developed a cell-pmca of vcjd, wherein cell lysate containing exogenously expressed human prp was used as substrates, to investigate the effe ...	2011	21565253
prion disease blood test using immunoprecipitation and improved quaking-induced conversion.	abstract a key challenge in managing transmissible spongiform encephalopathies (tses) or prion diseases in medicine, agriculture, and wildlife biology is the development of practical tests for prions that are at or below infectious levels. of particular interest are tests capable of detecting prions in blood components such as plasma, but blood typically has extremely low prion concentrations and contains inhibitors of the most sensitive prion tests. one of the latter tests is quaking-induced co ...	2011	21558432
polymorphisms of the prion protein gene and their effects on litter size and risk evaluation for scrapie in chinese hu sheep.	it is well known that scrapie is a fatal, neurodegenerative disease in sheep and goat, which belongs to the group of transmissible spongiform encephalopathies (tses) or prion diseases. it has been confirmed that the polymorphisms of prion protein gene (prnp) at codons 136, 154, and 171 have strong relationship with scrapie in sheep. in the present study, nine polymorphisms of prnp at codons 136, 154, and 171 and other six loci (at codons 101, 112, 127, 137, 138, and 152) were detected in 180 chi ...	2011	21556743
initial fate of prions upon peripheral infection: half-life, distribution, clearance, and tissue uptake.	prion diseases are infectious neurodegenerative disorders associated with the misfolded prion protein (prp(sc)), which appears to be the sole component of the infectious agent (termed prion). to produce disease, prions have to be absorbed into the body and reach sufficient quantities in the brain. very little is known about the biological mechanisms controlling the initial fate of prions. here, we studied the systemic pharmacokinetics and biodistribution of prp(sc) in vivo. after an intravenous ...	2011	21555356
iatrogenic concerns of the twentieth century: post-vaccinal encephalitis and spongiform encephalopathy.	throughout the twentieth century, iatrogenic disease constituted an enduring problem in western medical discourse and practice. a survey of the medical literature, investigative reports, and archival material indicates that iatrogenic concerns persisted throughout the century. two groups of case studies are presented: one associated with post-vaccinal encephalitis; the other, with the iatrogenically transmitted spongiform encephalopathies, scrapie and creutzfeldt-jakob disease. kuru, a similar d ...	2010	21553697
effect of glycans and the glycophosphatidylinositol anchor on strain dependent conformations of scrapie prion protein: improved purifications and infrared spectra.	mammalian prion diseases involve conversion of normal prion protein, prp(c), to a pathological aggregated state (prp(res)). the three-dimensional structure of prp(res) is not known, but infrared (ir) spectroscopy has indicated high, strain-dependent β-sheet content. prp(res) molecules usually contain a glycophosphatidylinositol (gpi) anchor and large asn-linked glycans, which can also vary with strain. using ir spectroscopy, we tested the conformational effects of these post-translational modifi ...	2011	21539311
genetic predisposition of some bulgarian sheep breeds to the scrapie disease.	the aim of this study is to investigate the profile of ovine prp gene by amino acid polymorphism at codons 136, 141, 154, and 171 for determining the genetic predisposition to the scrapie disease for the tribal sheep and rams, with different numbers and distribution in bulgaria. three hundred twenty four animals originating from 41 tribal herds comprising eight breeds were included in the study. dna was isolated from blood samples specifically amplified by pcr and sequenced. the alignments of co ...	2011	21533749
experimental oral transmission of atypical scrapie to sheep.	to investigate the possibility of oral transmission of atypical scrapie in sheep and determine the distribution of infectivity in the animals' peripheral tissues, we challenged neonatal lambs orally with atypical scrapie; they were then killed at 12 or 24 months. screening test results were negative for disease-specific prion protein in all but 2 recipients; they had positive results for examination of brain, but negative for peripheral tissues. infectivity of brain, distal ileum, and spleen fro ...	2011	21529394
genetics of prion disease.	prion diseases or transmissible spongiform encephalopathies (tses) are neurodegenerative disorders of humans and animals for which there are no effective treatments or cure. they include creutzfeldt-jakob disease (cjd) in humans and sheep scrapie, bovine spongiform encephalopathy (bse) and chronic wasting disease (cwd) in cervids. the prion protein (prp) is central to the disease process. an abnormal form of prp is generally considered to be the sole or principal component of the infectious agen ...	2011	21528440
replication and spread of cjd, kuru and scrapie agents in vivo and in cell culture.	transmissible spongiform encephalopathy (tse) agents are defined by their virulence for particular species, their spread in the population, their incubation time to cause disease, and their neuropathological sequelae. murine adapted human agents, including sporadic cjd (scjd), new guinea kuru, and japanese cjd agents, display particularly distinct incubation times and maximal infectious brain titers. they also induce agent-specific patterns of neurodegeneration. when these tse agents are transmi ...	2011	21527829
probing structural differences between prp(c) and prp(sc) by surface nitration and acetylation: evidence of conformational change in the c-terminus.	we used two chemical modifiers, tetranitromethane (tnm) and acetic anhydride (ac(2)o), which specifically target accessible tyrosine and lysine residues, respectively, to modify recombinant syrian hamster prp(90-231) [rshaprp(90-231)] and shaprp 27-30, the proteinase k-resistant core of prp(sc) isolated from brain of scrapie-infected syrian hamsters. our aim was to find locations of conformational change. modified proteins were subjected to in-gel proteolytic digestion with trypsin or chymotryps ...	2011	21526750
effects of solution chemistry and aging time on prion protein adsorption and replication of soil-bound prions.	prion interactions with soil may play an important role in the transmission of chronic wasting disease (cwd) and scrapie. prions are known to bind to a wide range of soil surfaces, but the effects of adsorption solution chemistry and long-term soil binding on prion fate and transmission risk are unknown. we investigated hy tme prion protein (prp(sc)) adsorption to soil minerals in aqueous solutions of phosphate buffered saline (pbs), sodium chloride, calcium chloride, and deionized water using w ...	2011	21526178
fate of prions in soil: a review.	prions are the etiological agents of transmissible spongiform encephalopathies (tsses), a class of fatal neurodegenerative diseases affecting humans and other mammals. the pathogenic prion protein is a misfolded form of the host-encoded prion protein and represents the predominant, if not sole, component of the infectious agent. environmental routes of tse transmission areimplicated in epizootics of sheep scrapie and chronic wasting disease (cwd) of deer, elk, and moose. soil represents a plausi ...	2011	21520752
effects of a brain-engraftable microglial cell line expressing anti-prion scfv antibodies on survival times of mice infected with scrapie prions.	we first verified that a single chain fv fragment against prion protein (anti-prp scfv) was secreted by hek293t cells and prevented prion replication in infected cells. we then stably expressed anti-prp scfv in brain-engraftable murine microglial cells and intracerebrally injected these cells into mice before or after infection with prions. interestingly, the injection before or at an early time point after infection attenuated the infection marginally but significantly prolonged survival times ...	2011	21516351
[polymorphism at codons 136, 141 and 154 in the ovine prion protein gene in the state of xinjiang].	scrapie is a fatal and infectious neurodegenerating disease. the polymorphism in the prion protein (prnp) gene is linked to the development of clinical signs of scrapie. the most important polymorphism appears to be at codons at 136(v/a), 154(h/r), and 171(h/q/r). in this study, we investigated the polymorphisms at these codons in 746 individuals among ten sheep breeds (i.e., aletai, bashibai, bayinbuluke, celehei, duolang, he tian, chinese merino, german merino, texel, and suffolk sheep) in xin ...	2010	21513168
aromatase expression in cultured fetal sheep astrocytes after nitrosative/oxidative damage.	aromatase, the enzyme converting androgens into estrogens, is involved in many brain processes such as neural differentiation and plasticity or the prevention of cell death. we have previously observed an increase in aromatase immunoreactivity in sheep neurons exposed in vitro to the oxidant 3-nitro-l: -tyrosine. however, little is known regarding the way that sheep astrocytes cope with nitrosative stress, a condition occurring in sheep in the pathogenesis of neurodegenerative disorders such as ...	2011	21509460
palladium complexes affect the aggregation of human prion protein prp106-126.	many neurodegenerative disorders are induced by protein conformational change. prion diseases are characterized by protein conformational conversion from a normal cellular form (prp(c)) to an abnormal scrapie isoform (prp(sc)). prp106-126 is an accepted model for studying the characteristics of prp(sc) because they share many biological and physiochemical properties. to understand how metal complexes affect the property of the prion peptide, the present work investigated interactions between pd ...	2011	21504185
transmission of prion strains in a transgenic mouse model overexpressing human a53t mutated α-synuclein.	there is a growing interest in the potential roles of misfolded protein interactions in neurodegeneration. to investigate this issue, we inoculated 3 prion strains intracerebrally into transgenic (tgm83) mice that overexpress human a53t α-synuclein. in comparison to nontransgenic controls, there was a striking decrease in the incubation periods of scrapie, classic and h-type bovine spongiform encephalopathies(c-bse and h-bse), with conservation of the histopathologic and biochemical features cha ...	2011	21487306
prions and protein-folding diseases.	abstract. norrby e (royal swedish academy of sciences, stockholm, sweden). prions and protein-folding diseases (review). j intern med 2011; doi: 10.1111/j.1365-2796.2011.02387.x prions represent a group of proteins with a unique capacity to fold into different conformations. one isoform is rich in beta-pleated sheets and can aggregate into amyloid that may be pathogenic. this abnormal form propagates itself by imposing its confirmation on the homologous normal host cell protein. pathogenic prio ...	2011	21481020
molecular discrimination of sheep bovine spongiform encephalopathy from scrapie.	sheep ch1641-like transmissible spongiform encephalopathy isolates have shown molecular similarities to bovine spongiform encephalopathy (bse) isolates. we report that the prion protein prpsc from sheep bse is extremely resistant to denaturation. this feature, combined with the n-terminal prpsc cleavage, allowed differentiation of classical scrapie, including ch1641-like, from natural goat bse and experimental sheep bse.	2011	21470463
molecular dynamics studies on the structural stability of wild-type dog prion protein.	prion diseases such as creutzfeldt-jakob disease, variant creutzfeldt-jakob diseases, gerstmann-sträussler-scheinker syndrome, fatal familial insomnia, kuru in humans, scrapie in sheep, bovine spongiform encephalopathy (or 'mad-cow' disease) and chronic wasting disease in cattle are invariably fatal and highly infectious neurodegenerative diseases affecting humans and animals. however, by now there have not been some effective therapeutic approaches to treat all these prion diseases. in 2008, ca ...	2011	21469747
investigation of the effects of experimental autolysis on the detection of abnormal prion protein in lymphoid and central nervous system tissues from elk and sheep using the western blotting method.	tissues unsuitable for standard immunohistochemical and histopathological examinations for chronic wasting disease (cwd) in cervids and for scrapie in sheep are frequently submitted for testing. this study investigated the effects of experimental autolysis on the detection of abnormal prion protein (prpsc) in lymphoid and central nervous system (cns) tissues from elk and sheep. the prpsc was detected using a western blotting (wb) test following prpsc enrichment using sodium phosphotungstic acid ...	2011	21461199
overexpression of shadoo protein in transgenic mice does not impact the pathogenesis of scrapie.	shadoo is a glycoprotein expressed in the adult brain that is an interacting protein of prion protein; however, its function remains to be determined. to elucidate its role in prion pathogenesis, we generated transgenic mice overexpressing wild-type (wt) shadoo driven by the murine prp promoter. expression of the murine sprn transgene significantly increased brain shadoo protein levels in all three mouse lines generated. following infection with mouse-adapted scrapie strain 22l, all transgenic m ...	2011	21458534
distinct proteinase k-resistant prion protein fragment in goats with no signs of disease in a classical scrapie outbreak.	considerable efforts have been directed toward the identification of small-ruminant prion diseases, i.e., classical and atypical scrapie as well as bovine spongiform encephalopathy (bse). here we report the in-depth molecular analysis of the proteinase k-resistant prion protein core fragment (prp(res)) in a highly scrapie-affected goat flock in greece. the prp(res) profile by western immunoblotting in most animals was that of classical scrapie in sheep. however, in a series of clinically healthy ...	2011	21450953
deduction of the evaluation limit and termination timing of multi-round protein misfolding cyclic amplification from a titration curve.	in this study, the efficacy of disinfectants in reducing the partially protease-resistant isoform of prion protein was evaluated by a multi-round protein misfolding cyclic amplification (pmca) technique. hamster brains infected with scrapie-derived strain 263k were homogenized, treated under inactivating or mock conditions, and subjected to multi-round pmca. four sets of serial 10-fold dilutions of mock-treated samples were analyzed. although considerable variability was observed in the signal p ...	2011	21443616
the cellular prion protein mediates neurotoxic signalling of ß-sheet-rich conformers independent of prion replication.	formation of aberrant protein conformers is a common pathological denominator of different neurodegenerative disorders, such as alzheimer's disease or prion diseases. moreover, increasing evidence indicates that soluble oligomers are associated with early pathological alterations and that oligomeric assemblies of different disease-associated proteins may share common structural features. previous studies revealed that toxic effects of the scrapie prion protein (prp(sc)), a ß-sheet-rich isoform o ...	2011	21441896
blocking of fcr suppresses the intestinal invasion of scrapie agents.	prion diseases are a family of neurodegenerative zoonotic foodborne disorders. although prions can be transmitted orally, the mechanism by which prions are incorporated into the intestine remains unclear. our previous studies have shown that an abnormal isoform of prion protein (prp(sc)), which is the main component of prions, was efficiently incorporated into the intestine in suckling mice but not in weaned mice. furthermore, suckling scid mice lacking maternal antibodies showed decreased uptak ...	2011	21437246
replication efficiency of soil-bound prions varies with soil type.	prion sorption to soil is thought to play an important role in the transmission of scrapie and chronic wasting disease (cwd) via the environment. sorption of prp to soil and soil minerals is influenced by the strain and species of prp(sc) and by soil characteristics. however, the ability of soil-bound prions to convert prp(c) to prp(sc) under these wide-ranging conditions remains poorly understood. we developed a semiquantitative protein misfolding cyclic amplification (pmca) protocol to evaluat ...	2011	21430062
synthesis, structural characterization, formation constants and in vitro cytotoxicity of phenanthroline and imidazolidine-2-thione copper(ii) complexes.	the synthesis, crystal structures, physicochemical properties and complex formation constants of [cu(phen)(2)(l)](clo(4))(2) complexes, where phen is 1,10-ortho-phenanthroline and l is a series of substituted imidazolidine-2-thione, have been studied. single crystal x-ray diffraction revealed a distorted trigonal-bipyramidal geometry for all the molecules. the complex formation constants were determined in nonaqueous media by spectrophotometric measurements. testing copper(ii) complexes in mouse ...	2011	21421120
medical microbiology	subacute progressive degenerative diseases of the nervous system are important because they appear to be caused by infectious agents that are smaller than conventional viruses and composed mainly of protein related to a cell protein. few, if any, of these diseases are curable. although some are genetically determined, most occur sporadically, and a history of the disease does not appear in close relatives. therefore, ...	1996	21413288
hybrid lipoic acid derivatives to attack prion disease on multiple fronts.		2011	21412985
a study on the analytical sensitivity of 6 bse tests used by the canadian bse reference laboratory.	bovine spongiform encephalopathy (bse) surveillance programs have been employed in numerous countries to monitor bse prevalence and to protect animal and human health. since 1999, the european commission (ec) authorized the evaluation and approval of 20 molecular based tests for the rapid detection of the pathological prion protein (prp(sc)) in bse infection. the diagnostic sensitivity, convenience, and speed of these tests have made molecular diagnostics the preferred method for bse surveillanc ...	2011	21412419
[active surveillance for scrapie in the netherlands: effect of a breeding programme on the prevalence of scrapie in sheep (2002-2010)?].	the susceptibility of sheep to scrapie is modulated by the prion protein (prp) genotype of the animal. an ambitious voluntary scrapie control programme was started in the netherlands in 1998, based on selection of rams with thearr/arr genotype for breeding. this programme was followed by an obligatory programme in 2004; the programme has been voluntary since 2007. we monitored the prevalence of prp genotype frequencies and the prevalence of scrapie in the dutch sheep population between 2002 and ...	2011	21404540
survival of infectious prions in class b biosolids.	this study developed a method for extracting infectious prions from class b biosolids and subsequently evaluated the survival of infectious prions under the influence of mesophilic (37-¦c) and thermophilic (60-¦c) temperatures in class b biosolids. unlike other studies, this study utilized a scrapie cell assay to determine infectivity and quantity of infectious prions. the best method for extraction was exposing the biosolids to 4 m urea at 80-¦c for 10 minutes followed by a membrane centrifugat ...	2011	21391030
differential targeting of neurons by prion strains.	a basic principle of microbiology that applies to all conventional infectious pathogens is that the disease phenotype is a function of both the infecting agent and the host's response to it. all evidence indicates that this principle is also true for diseases acquired by infection with prions, given that inoculation of different scrapie prion strains into inbred mouse strains shows that reproducible differences in the disease phenotype are determined by both the strain of scrapie prion and a hos ...	2001	21374500
characterization of bovine spongiform encephalopathy and scrapie strains/isolates by immunochemical analysis of prpsc.	in the past two decades, thoroughly standardized mouse incubation time and brain lesion profile scoring assays have been developed to discriminate between prion strains. however, in these mouse infection experiments, large numbers of animals (about 20 mice/line) from three different highly inbred mouse lines (c57bl, vm95, riii), plus their intercrosses, need to be infected, and their brain tissues subsequently examined (1-8). although results obtained are highly reliable, the effort and time nee ...	2001	21374499
prion protein peptide : agents of death for neurons.	the fundamental problem in addressing prion diseases, or the transmissible spongiform encephalopathies, is finding an explanation for the massive neuronal death that occurs. although some understanding of the mechanism by which neuronal death occurs comes from studies with scrapie-infected mice, most of the insights regarding a possible mechanism have come from cell culture models in which a synthetic peptide (prp106-126), based on the sequence of the prion protein, has been applied to neuronal ...	2001	21374498
sc237 hamster prpsc and sc237-derived mouse prpsc generated by interspecies in vitro amplification exhibit distinct pathological and biochemical properties in tga20 transgenic mice.	prions are the infectious agents responsible for transmissible spongiform encephalopathy, and are primarily composed of the pathogenic form (prp(sc)) of the host-encoded prion protein (prp(c)). recent studies have revealed that protein misfolding cyclic amplification (pmca), a highly sensitive method for prp(sc) detection, can overcome the species barrier in several xenogeneic combinations of prp(sc) seed and prp(c) substrate. although these findings provide valuable insight into the origin and ...	2011	21362027
features of follicular dendritic cells in ovine pharyngeal tonsil: an in vivo and in vitro study in the context of scrapie pathogenesis.	although the alimentary tract has been suggested as the most likely portal of entry in natural scrapie, a growing amount of data indicates that the respiratory system and more specifically the pharyngeal tonsils serve as a natural portal of entry for scrapie. this study describes for the first time the broad cell populations in the lymphoid compartment of pharyngeal tonsils and more specifically inside the lymphoid follicles where the scrapie agent accumulates during the period of latency. folli ...	2011	21353313
prion propagation and toxicity in vivo occur in two distinct mechanistic phases.	mammalian prions cause fatal neurodegenerative conditions including creutzfeldt-jakob disease in humans and scrapie and bovine spongiform encephalopathy in animals. prion infections are typically associated with remarkably prolonged but highly consistent incubation periods followed by a rapid clinical phase. the relationship between prion propagation, generation of neurotoxic species and clinical onset has remained obscure. prion incubation periods in experimental animals are known to vary inver ...	2011	21350487
highly efficient protein misfolding cyclic amplification.	protein misfolding cyclic amplification (pmca) provides faithful replication of mammalian prions in vitro and has numerous applications in prion research. however, the low efficiency of conversion of prp(c) into prp(sc) in pmca limits the applicability of pmca for many uses including structural studies of infectious prions. it also implies that only a small sub-fraction of prp(c) may be available for conversion. here we show that the yield, rate, and robustness of prion conversion and the sensit ...	2011	21347353
atypical/nor98 scrapie infectivity in sheep peripheral tissues.	atypical/nor98 scrapie was first identified in 1998 in norway. it is now considered as a worldwide disease of small ruminants and currently represents a significant part of the detected transmissible spongiform encephalopathies (tse) cases in europe. atypical/nor98 scrapie cases were reported in arr/arr sheep, which are highly resistant to bse and other small ruminants tse agents. the biology and pathogenesis of the atypical/nor98 scrapie agent in its natural host is still poorly understood. how ...	2011	21347349
biological effects and use of prpsc- and prp-specific antibodies generated by immunization with purified full-length native mouse prions.	the prion agent is the infectious particle causing spongiform encephalopathies in animals and humans and is thought to consist of an altered conformation (prp(sc)) of the normal and ubiquitous prion protein prp(c). the interaction of the prion agent with the immune system, particularly the humoral immune response, has remained unresolved. here we investigated the immunogenicity of full-length native and infectious prions, as well as the specific biological effects of the resulting monoclonal ant ...	2011	21345946
prion diseases of yeast: amyloid structure and biology.	prion "variants" or "strains" are prions with the identical protein sequence, but different characteristics of the prion infection: e.g. different incubation periods for scrapie strains or different phenotype intensities for yeast prion variants. we have shown that infectious amyloids of the yeast prions [psi+], [ure3] and [pin+] each have an in-register parallel ß-sheet architecture. moreover, we have pointed out that this amyloid architecture can explain how one protein can faithfully transmit ...	2011	21345375
subcellular localization of peptidylarginine deiminase 2 and citrullinated proteins in brains of scrapie-infected mice: nuclear localization of pad2 and membrane fraction-enriched citrullinated proteins.	peptidylarginine deiminase (pad) and citrullinated proteins have emerged as key molecules in various human diseases, but detailed subcellular localizations of pad2 and citrullinated proteins are poorly mapped in brain under normal and pathologic conditions. we performed subcellular fractionation and electron microscopic analysis using brains of normal and scrapie-infected mice. peptidylarginine deiminase 2 was abundantly present in cytosol and weakly in microsomal and mitochondrial fractions and ...	2011	21343880
normal modes of prion proteins: from native to infectious particle.	prion proteins (prp) are the infectious agent in transmissible spongiform encephalopathies (i.e., mad cow disease). to be infectious, prion proteins must undergo a conformational change involving a decrease in a-helical content along with an increase in ß-strand content. this conformational change was evaluated by means of elastic normal modes. elastic normal modes show a diminution of two a-helices by one and two residues, as well as an extension of two ß-strands by three residues each, which c ...	2011	21338080
prpsc spreading patterns in the brain of sheep linked to different prion types.	abstract: scrapie in sheep and goats has been known for more than 250 years and belongs nowadays to the so-called prion diseases that also include e.g. bovine spongiform encephalopathy in cattle (bse) and creutzfeldt-jakob disease in humans. according to the prion hypothesis, the pathological isoform (prpsc) of the cellular prion protein (prpc) comprises the essential, if not exclusive, component of the transmissible agent. currently, two types of scrapie disease are known - classical and atypic ...	2011	21324114
the impact of the genotype on the prevalence of classical scrapie at population level.	abstract: total number and genotypes of animals in holdings selected for the genotype & cull option in the compulsory scrapie flock scheme (csfs) in great britain were extracted from the national scrapie plan data warehouse. the association between various genotype-related measures and scrapie prevalence infection was tested using zero-inflated negative binomial models with the counts of positive cases as dependent variable, and country, number of flocks in the scheme, flock size, surveillance s ...	2011	21324113
effects of polymorphisms in ovine and caprine prion protein alleles on cell-free conversion.	abstract: in sheep polymorphisms of the prion gene (prnp) at the codons 136, 154 and 171 strongly influence the susceptibility to scrapie and bovine spongiform encephalopathy (bse) infections. in goats a number of other gene polymorphisms were found which are suspected to trigger similar effects. however, no strong correlation between polymorphisms and tse susceptibility in goats has yet been obtained from epidemiological studies and only a low number of experimental challenge data are available ...	2011	21324112
expression patterns of prion protein gene in differential genotypes sheep: quantification using molecular beacon real-time rt-pcr.	determination of the transcription level of cellular prion protein (prp(c)) is essential for understanding its role in organisms and revealing mechanism of susceptibility and resistance to scrapie. however, the expression of prion protein (prp) mrna in sheep has not been quantified in great detail in digestive tract which is important during scrapie spread through oral route. herein, we report on measurement of sheep prp mrna using absolute quantitative real-time rt-pcr. total rna was isolated f ...	2011	21318242
changes in hsp gene and protein expression in natural scrapie with brain damage.	abstract: heat shock proteins (hsp) perform cytoprotective functions such as apoptosis regulation and inflammatory response control. these proteins can also be secreted to the extracellular medium, acting as inflammatory mediators, and their chaperone activity permits correct folding of proteins and avoids the aggregation of anomalous isoforms. several studies have proposed the implication of hsp in prion diseases. we analysed the gene expression and protein distribution of different members of ...	2011	21314976
breeding with resistant rams leads to rapid control of classical scrapie in affected sheep flocks.	abstract: susceptibility to scrapie, a transmissible spongiform encephalopathy in sheep, is modulated by the genetic make-up of the sheep. scrapie control policies, based on selecting animals of resistant genotype for breeding, have recently been adopted by the netherlands and other european countries. here we assess the effectiveness of a breeding programme based on selecting rams of resistant genotype to obtain outbreak control in classical scrapie-affected sheep flocks under field conditions. ...	2011	21314971
in situ photodegradation of incorporated polyanion does not alter prion infectivity.	single-stranded polyanions =40 bases in length facilitate the formation of hamster scrapie prions in vitro, and polyanions co-localize with prp(sc) aggregates in vivo. to test the hypothesis that intact polyanionic molecules might serve as a structural backbone essential for maintaining the infectious conformation(s) of prp(sc), we produced synthetic prions using a photocleavable, 100-base oligonucleotide (pc-oligo). in serial protein misfolding cyclic amplification (spmca) reactions using purif ...	2011	21304885
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 ...	2010	21294124
transmission of classical scrapie to wild-type mice: the influence of the ovine prp sequence on lesion profiles.	susceptibility of sheep to classical scrapie is determined by polymorphisms in the coding region of the prion protein gene (prnp), mainly at codons 136, 154 and 171. it has recently been shown that lesion profiles from classical field scrapie isolates that transmitted to riii mice can be classified into different groups. there was also strong, but not absolute, association between the different groups and codon 136. here, we examine the hypothesis that additional polymorphisms in the open readin ...	2011	21293966
utility of mass spectrometry in the diagnosis of prion diseases.	we developed a sensitive mass spectrometry-based method of quantitating the prions present in a variety of mammalian species. calibration curves relating the area ratios of the integrated mrm signals from selected analyte peptides and their oxidized analogues to their homologous stable isotope labeled internal standards were prepared. the limit of detection (lod) and limit of quantitation (loq) for the synthetic peptides from human, sheep, deer, cow, and mouse prp were determined to be below 100 ...	2011	21288014
sparse prp(sc) accumulation in the placentas of goats with naturally acquired scrapie.	domestic goats (capra hircus) are a natural and experimental host of scrapie and bovine spongiform encephalopathy, the transmissible spongiform encephalopathies (tse) of sheep and cattle. goats are also susceptible to experimental infection with the agents of tses of deer and elk (chronic wasting disease) and humans (creutzfeldt jakob disease). distribution of prpsc, the abnormal prion protein, is similar in the tissues of scrapie-infected sheep and goats but no data are available on the potenti ...	2011	21284878
fundamentals of prions and their inactivation (review).	prion is an infectious particle composed of an abnormal isoform of the prion protein (prpsc) and causes prion diseases such as bovine spongiform encephalopathy (bse), creutzfeldt-jakob disease (cjd) and scrapie. host cells express cellular prion protein (prpc), which plays roles in normal functions such as anti-oxidative stress. prpsc is derived from prpc and produced by conformational conversion. prion is notorious as a resistant pathogen, being difficult to inactivate with conventional sterili ...	2011	21271212
emergence of multiple prion strains from single isolates of ovine scrapie.	the infectious agent associated with prion diseases such as ovine scrapie shows strain diversity. ovine prion strains have typically been identified by their transmission properties in wild-type mice. however, strain typing of ovine scrapie isolates in wild-type mice may not reveal properties of the infectious prion agent as they exist in the original host. this could be circumvented if ovine scrapie isolates are passaged in ovine prion protein (prp)-transgenic mice. this study used incubation t ...	2011	21270287
comparative performance of three tse rapid tests for surveillance in healthy sheep affected by scrapie.	rapid tests specific for sheep and goats became part of european union-wide active scrapie surveillance in 2006. performance of three approved tse rapid tests for the detection of sheep infected with scrapie in field cases in the pre-clinical stage of the disease was compared. the medulla oblongata of 969 asymptomatic sheep of various genotype and breed aged over 18 months from 23 italian flocks affected with scrapie, were tested by the bio-rad tesee sheep/goat (a), the idexx herdchek bse-scrapi ...	2011	21256871
aerosols transmit prions to immunocompetent and immunodeficient mice.	prions, the agents causing transmissible spongiform encephalopathies, colonize the brain of hosts after oral, parenteral, intralingual, or even transdermal uptake. however, prions are not generally considered to be airborne. here we report that inbred and crossbred wild-type mice, as well as tga20 transgenic mice overexpressing prp(c), efficiently develop scrapie upon exposure to aerosolized prions. nse-prp transgenic mice, which express prp(c) selectively in neurons, were also susceptible to ai ...	2011	21249178
comparison of brain prpd distribution in ovine bse and scrapie.	scrapie and bovine spongiform encephalopathy (bse) are both prion diseases affecting ruminants, and these diseases do not share the same public health concerns. surveillance of the bse agent in small ruminants has been a great challenge, and the recent identification of diverse prion diseases in ruminants has led to the development of new methods for strain typing. in our study, using immunohistochemistry (ihc), we assessed the distribution of prp(d) in the brains of 2 experimentally bse-infecte ...	2011	21245284
glycosylphosphatidylinositol anchor-dependent stimulation pathway required for generation of baculovirus-derived recombinant scrapie prion protein.	the pathogenic isoform (prp(sc)) of the host-encoded cellular prion protein (prp(c)) is considered to be an infectious agent of transmissible spongiform encephalopathy (tse). the detailed mechanism by which the prp(sc) seed catalyzes the structural conversion of endogenous prp(c) into nascent prp(sc) in vivo still remains unclear. recent studies reveal that bacterially derived recombinant prp (recprp) can be used as a substrate for the in vitro generation of protease-resistant recprp (recprp(res ...	2011	21228241
extraneural manifestations of prion infection in gpi-anchorless transgenic mice.	earlier studies indicated that transgenic (tg) mice engineered to express prion protein (prp) lacking the glycophosphatidylinositol (gpi⁻/⁻) membrane anchor formed abnormal proteinase-resistant prion (prpsc) amyloid deposits in their brains and hearts when infected with the rml strain of murine scrapie. in contrast, rml scrapie infection of normal mice with a gpi-anchored prp did not deposit amyloid with prpsc in the brain or the heart. here we report that scrapie-infected gpi⁻/⁻ prp tg mice als ...	2011	21227476
the effects of lysosomal and proteasomal inhibitors on abnormal forms of prion protein degradation in murine macrophages.	it has been reported that macrophages degrade infectious forms of prion protein (prp(sc) ). in order to investigate the mechanisms underlying prp(sc) degradation in macrophages, the effects of lysosomal and proteasomal inhibitors on macrophage cell lines which were incubated with scrapie-affected brain homogenate were studied. prp(sc) degradation was inhibited in the presence of both proteasomal and lysosomal inhibitors. indirect fluorescence assays to determine the cellular localization of prp( ...	2010	21223366
prion protein misfolding affects calcium homeostasis and sensitizes cells to endoplasmic reticulum stress.	prion-related disorders (prds) are fatal neurodegenerative disorders characterized by progressive neuronal impairment as well as the accumulation of an abnormally folded and protease resistant form of the cellular prion protein, termed prp(res). altered endoplasmic reticulum (er) homeostasis is associated with the occurrence of neurodegeneration in sporadic, infectious and familial forms of prds. the er operates as a major intracellular calcium store, playing a crucial role in pathological event ...	2010	21209925
spiroplasma found in the eyes of scrapie affected sheep.	scrapie, a transmissible spongiform encephalopathy (tse) occurring naturally in sheep, characteristically shows a severe retinopathy that is well developed in the terminal phases of the disease. in this study, we set out to demonstrate similar retinal changes in our ruminant spiroplasmosis tse model.	2011	21199275
biological properties of the prp-like shadoo protein.	the sprn gene encodes the shadoo glycoprotein (sho), a central nervous system-expressed member of the prion protein superfamily. sho has similarity to two features within prpc's natively unstructured n-terminus, a hydrophobic domain and tandem repeats with positively charged residues. indeed, scrutiny of sho's biochemical properties in uninfected cells has revealed overlaps with the properties of prpc, these including shared protein binding partners. sprn is conserved in mammals, as is the prion ...	2011	21196244
understanding the neurospecificity of prion protein signaling.	the cellular prion protein prp(c) is the normal counterpart of the scrapie prion protein prp(sc), the main component of the infectious agent of transmissible spongiform encephalopathies (tses). it is a ubiquitous cell-surface glycoprotein, abundantly expressed in neurons, which constitute the targets of tse pathogenesis. the presence of prp(c) at the surface of neurons is an absolute requirement for the development of prion diseases and corruption of prp(c) function(s) within an infectious conte ...	2011	21196165