Prion protein (PrP) is a membrane glycosylphosphatidylinositol (GPI)-anchored glycoprotein that is encoded by the PRNP gene and is highly conserved among mammals. PrP contains an unstable region consisting of five octapeptide repeats; mutations in this region are associated with Creutzfeldt-Jakob disease (CJD), fatal familial insomnia, Gerstmann-Straussler disease, Huntington disease-like 1, and kuru (a type of transmissible spongiform encephalopathy, TSE). The function of PrP is not clear, although it is known to bind copper ions. PrP exists as a normal cellular isoform (PrPC) that can undergo refolding to a conformational isoform known as scrapie isoform (PrPSc). PrPSc forms compact aggregates that are highly resistant to proteolysis. The conversion of PrPC to PrPSc is postulated to be the mechanism involved in transmission of TSEs. PrP is also known as prion protein (p27-30); major prion protein, prion-related protein, CJD, GSS, ASCR, KURU, PRIP, PrPc, CD230, AltPrP, p27-30, PrP27-30, and ...
Prion protein (PrP) is a membrane glycosylphosphatidylinositol (GPI)-anchored glycoprotein that is encoded by the PRNP gene and is highly conserved among mammals. PrP contains an unstable region consisting of five octapeptide repeats; mutations in this region are associated with Creutzfeldt-Jakob disease (CJD), fatal familial insomnia, Gerstmann-Straussler disease, Huntington disease-like 1, and kuru (a type of transmissible spongiform encephalopathy, TSE). The function of PrP is not clear, although it is known to bind copper ions. PrP exists as a normal cellular isoform (PrPC) that can undergo refolding to a conformational isoform known as scrapie isoform (PrPSc). PrPSc forms compact aggregates that are highly resistant to proteolysis. The conversion of PrPC to PrPSc is postulated to be the mechanism involved in transmission of TSEs. PrP is also known as prion protein (p27-30); major prion protein, prion-related protein, CJD, GSS, ASCR, KURU, PRIP, PrPc, CD230, AltPrP, p27-30, PrP27-30, and ...
Define transmissible neurodegenerative disease. transmissible neurodegenerative disease synonyms, transmissible neurodegenerative disease pronunciation, transmissible neurodegenerative disease translation, English dictionary definition of transmissible neurodegenerative disease. n. 1. An abnormal condition of a part, organ, or system of an organism resulting from various causes, such as infection, inflammation, environmental...
Prion protein is the causative agent of the transmissible spongiform encephalopathies. According to the "prion hypothesis," the infectious isoform of prion protein, termed PrPSc, replicates by interacting with cellular PrPC and mediating its conformational change into the disease-causing PrPSc (19). Compared with its well-defined pathological significance, the physiological function of PrPC remains unclear. PrPC is highly expressed not only by cells in the CNS but also by follicular DCs, mature myeloid cells, and activated T cells. This distribution suggests involvement of PrPC in immune surveillance (20).. Our present study defines a novel role for PrPC as an M-cell receptor for the uptake of pathogenic bacteria. PrPC on macrophages has been reported to recognize surface-exposed Hsp60 of B. abortus and to facilitate internalization of the bacteria (13); however, Fontes et al. (21) reported a contradictory result. Using Prnp−/− mice, they showed that B. suis infection is independent of PrPC ...
Background Imbalance of iron homeostasis has been reported in sporadic Creutzfeldt-Jakob-disease (sCJD) affected human and scrapie infected animal brains, but the contribution of this phenotype to disease associated neurotoxicity is unclear. Methodology/Principal Findings Using cell models of familial prion disorders, we demonstrate that exposure of cells expressing normal prion protein (PrPC) or mutant PrP forms to a source of redox-iron induces aggregation of PrPC and specific mutant PrP forms. Initially this response is cytoprotective, but becomes increasingly toxic with time due to accumulation of PrP-ferritin aggregates. Mutant PrP forms that do not aggregate are not cytoprotective, and cells show signs of acute toxicity. Intracellular PrP-ferritin aggregates induce the expression of LC3-II, indicating stimulation of autophagy in these cells. Similar observations are noted in sCJD and scrapie infected hamster brains, lending credence to these results. Furthermore, phagocytosis of PrP-ferritin
Prions are the enigmatic etiological agents of transmissible spongiform encephalopathies (TSEs), 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 are implicated in epizootics of sheep scrapie and chronic wasting disease of deer, elk, and moose. Soil is the most plausible candidate for preserving prion infectivity in the environment. We have investigated prion attachment to and detachment from inorganic and organic soil particle surfaces and examined the effect of association with specific soil constituents on disease transmission. Interaction of prions with some phyllosilicate mineral surfaces is remarkably strong. Interestingly, rather than diminishing bioavailability, attachment to such particles enhances disease transmission. This finding suggests an explanation ...
Following intracerebral or peripheral inoculation of mice with scrapie prions, infectivity accumulates first in the spleen and only later in the brain. In the spleen of scrapie-infected mice, prions were found in association with T and B lymphocytes and to a somewhat lesser degree with the stroma, which contains the follicular dendritic cells (FDCs) but not with non-B, non-T cells; strikingly, no infectivity was found in lymphocytes from blood of the same mice. Transgenic PrP knockout mice expressing PrP restricted to either B or T lymphocytes show no prion replication in the lymphoreticular system. Therefore, splenic lymphocytes either acquire prions from another source or replicate them in dependency on other PrP-expressing cells. The essential role of FDCs in prion replication in spleen was shown by treating mice with soluble lymphotoxin-β receptor, which led to disappearance of mature FDCs from the spleen and concomitantly abolished splenic prion accumulation and retarded neuroinvasion ...
Conformational intermediates of the human prion protein huPrPC were characterized by a combination of hydrostatic pressure (up to 200 MPa) with two-dimensional NMR spectroscopy. All pressure effects showed to be reversible and there is virtually no difference in the overall pressure response between the folded core of the N-terminal truncated huPrPC(121-230) and the full-length huPrPC(23-230). The only significant differences in the pressure response of full-length and truncated PrP suggest that E168, H187, T192, E207, E211 and Y226 are involved in a transient interaction with the unfolded N-terminus. High-pressure NMR spectroscopy indicates that the folded core of the human prion protein occurs in two structural states N1and N2 in solution associated with rather small differences in free enthalpies (3.0 kJ/mol). At atmospheric pressure approximately 29% of the protein are already in the pressure favored conformation N2. There is a second process representing two possible folding intermediates ...
Single nucleotide polymorphisms (SNPs) and haplotype alleles within the prion gene (PRNP) coding sequence of domestic sheep (Ovis aries) are associated with genetic predisposition to scrapie, a transmissible spongiform encephalopathy disease of sheep. This report describes regions of linkage disequilibrium (LD) throughout the PRNP gene region in U.S. sheep and provides a genetic framework for identifying additional PRNP determinants associated with scrapie resistance. Four sequence tagged sites (i.e., STS or amplicons) totaling 3869 bp and spanning 20 kbp of genomic PRNP sequence were sequenced in a diverse panel of 90 sires representing ten popular U.S. breeds of sheep. Analysis of these sequences identified 36 previously unreported polymorphisms. In combination with two previously characterized STS, 62 polymorphisms were analyzed in a 20-kbp PRNP region in this panel of U.S. sheep. Two regions of strong LD and ten common haplotypes were identified. The haplotype encoding amino acid residues A, R, and
Conversion of prion protein (PrP) to an altered conformer, the scrapie PrP (PrPSc), is a critical step in the development of transmissible spongiform encephalopathies. Both Cu(II) and nucleic acid molecules have been implicated in this conversion. Full-length PrP can bind up to six copper ions; four Cu(II) binding sites are located in the octarepeat domain (residues 60-91), and His-96 and His-111 coordinate two additional copper ions. Experimental evidence shows that PrP binds different molecules, resulting in diverse cellular signaling events. However, there is little information about the interaction of macromolecular ligands with Cu(II)-bound PrP. Both RNA and DNA sequences can bind PrP, and this interaction results in reciprocal conformational changes. Here, we investigated the interaction of Cu(II) and nucleic acids with amyloidogenic non-octarepeat PrP peptide models (comprising human PrP residues 106-126 and hamster PrP residues 109-149) that retain His-111 as the copper-anchoring residue. The
Zanusso, G; Liu, D; Ferrari, S; Hegyi, I; Yin, X; Aguzzi, A; Hornemann, S; Liemann, S; Glockshuber, R; Manson, J C; Brown, P; Petersen, R B; Gambetti, P; Sy, M S (1998). Prion protein expression in different species: analysis with a panel of new mAbs. Proceedings of the National Academy of Sciences of the United States of America (PNAS), 95(15):8812-8816.. Raeber, A J; Race, R E; Brandner, S; Priola, S A; Sailer, A; Bessen, R A; Mucke, L; Manson, J C; Aguzzi, A; Oldstone, M B; Weissmann, C; Chesebro, B (1997). Astrocyte-specific expression of hamster prion protein (PrP) renders PrP knockout mice susceptible to hamster scrapie. EMBO Journal, 16(20):6057-6065.. ...
23284 Comment by Andrea LeBlanc: This interesting paper shows that quite a few of the disease-associated human prion mutations actually switch to the normal Doppel sequence. The doppel (i.e., "doppelgaenger") gene is downstream of the PrP gene. Its protein resembles amino-terminally truncated PrP and interacts with PrP.) Doppel overexpression is neurotoxic. Therefore, the switch of PrP into a Doppel-like protein could indicate that Doppel and mutant PrP are neurotoxic through a similar mechanism. However, it remains to be seen if these mutant PrPs are neurotoxic or not.. Our work has focused on the function of normal prion protein in primary human neurons. I suspected a function for prion protein in cell death or cell survival because of some similarity between the BH2 domain of Bcl-2 proteins and the octapeptide repeat of prion protein. While we now know that PrP is not a member of the Bcl-2 family of proteins, it is, however, a strong neuroprotective agent against Bax-mediated cell death. We ...
Team:Valencia/head}} ,div id="HomeCenter"> ,div id="Titulos"> Regulating Mars temperature ,br> ,br> using a prion switch ,/div> ,br> ==Prions== In 1982 Stanley B. Prusiner created the term "prion" (or proteinacius infectious particle) to name the exclusively proteic infectious agent responsible of the transmissible spongiform encephalopathies (TSEs), a group of mammalian neurodegenerative disorders. According to the widely supported "protein-only" model, the prion mechanism of transmissibility arise from the ability of the prion form of the protein to promote the conformational change of the normal cellular form to the infectious prion forms (Prusiner, 1998). The infectious forms are mis-folded proteins that induce by polymerization the formation of an amyloid fold constituted by tightly packed beta sheets. These aggregates are insoluble fibrils that display resistance to proteolytic digestion and have affinity for aromatic dyes. ===Fungal prions=== In 1994 Reed Wickner proposed the prion nature ...
TY - JOUR. T1 - Structure-based view on [PSI+] prion properties. AU - Bondarev, S.A.. AU - Zhouravleva, G.A.. AU - Belousov, M.V.. AU - Kajava, A.V.. PY - 2015. Y1 - 2015. N2 - Yeast [PSI+] prion is one of the most suitable and well characterized system for the investigation of the prion phenomenon. However, until recently, the lack of data on the 3D arrangement of Sup35p prion fibrils hindered progress in this area. The recent arrival in this field of new experimental techniques led to the parallel and in-register superpleated β-structure as a consensus model for Sup35p fibrils. Here, we analyzed the effect of amino acid substitutions of the Sup35 protein through the prism of this structural model. Application of a newly developed computational approach, called ArchCandy, gives us a better understanding of the effect caused by mutations on the fibril forming potential of Sup35 protein. This bioinformatics tool can be used for the design of new mutations with desired modification of prion ...
In this study, we characterized the biochemical properties of a set of chimeric prion proteins wherein the ORD of Sup35p was replaced with that of PrP. The chimeric prion proteins were created by substituting the endogenous Sup35p ORD with the repeat domain of PrP containing five, eight, 11 and 14 oligopeptide repeats [40]. The repeat-expanded proteins show a remarkable set of properties that highlight their enhanced ability to aggregate and form amyloid fibers in vitro. These data agree with work done by others in which recombinant PrP (rPrP) with ORD expansions exhibit an enhanced ability to form amyloid fibers with increasing number of repeats [20, 46]. Our data also support previous work done with transgenic mice (Tg(PG14)) that express PrP harboring nine additional octapeptide repeats. These mice manifest a spontaneous form of prion disease [21]. Although the spontaneous form of the disease in the Tg(PG14) mice is not infectious, the protein aggregates and the animals display many of the ...
Prion protein 2 (dublet), also known as PRND, or Doppel protein, is a protein which in humans is encoded by the PRND gene. This gene is found on chromosome 20, approximately 20 kbp downstream of the gene encoding cellular prion protein, to which it is biochemically and structurally similar. The protein encoded by this gene is a membrane glycosylphosphatidylinositol-anchored glycoprotein that is found predominantly in testis. Mutations in this gene may lead to neurological disorders. GRCh38: Ensembl release 89: ENSG00000171864 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000098754 - Ensembl, May 2017 "Human PubMed Reference:". "Mouse PubMed Reference:". "Entrez Gene: PRND prion protein 2 (dublet)". Moore RC, Lee IY, Silverman GL, et al. (1999). "Ataxia in prion protein (PrP)-deficient mice is associated with upregulation of the novel PrP-like protein doppel". J. Mol. Biol. 292 (4): 797-817. doi:10.1006/jmbi.1999.3108. PMID 10525406. Weissmann C, Aguzzi A (1999). "Perspectives: ...
The role of carcinine in signaling at the Drosophila photoreceptor synapse. Gavin BA, Arruda SE, Dolph PJ. PLoS Genet. 2007 Dec;3(12):e206. PMID: 18069895 [PubMed - indexed for MEDLINE]. Accelerated accumulation of misfolded prion protein and spongiform degeneration in a Drosophila model of Gerstmann-Sträussler-Scheinker syndrome. Gavin BA, Dolph MJ, Deleault NR, Geoghegan JC, Khurana V, Feany MB, Dolph PJ, Supattapone S. J Neurosci. 2006 Nov 29;26(48):12408-14. PMID: 17135402 [PubMed - indexed for MEDLINE]. An essential role for endocytosis of rhodopsin through interaction of visual arrestin with the AP-2 adaptor. Orem NR, Xia L, Dolph PJ. J Cell Sci. 2006 Aug 1;119(Pt 15):3141-8. Epub 2006 Jul 11. PMID: 16835270 [PubMed - indexed for MEDLINE]. Molecular cloning of the pawn locus from Drosophila melanogaster. Arruda SE, Dolph PJ. Gene. 2003 May 22;310:169-73. PMID: 12801644 [PubMed - indexed for MEDLINE]. Post-transcriptional suppression of pathogenic prion protein expression in Drosophila ...
Egg candling gadget made by the BE department. An egg candling gadget is used to identify infertile eggs and monitor the development of embryos. Chicken embryos were used for tick research in the yolk sac method ...
In the central nervous system, cellular prion proteins are found in astrocytes and neurons. There has been evidence showing that they prolong the survival9 as well as affect the differentiation of these structures. Scientists have found that cellular prions interact with NCAM, neuronal cell adhesion molecules, in astrocytes and this causes neurogenesis. Another role that the cellular prions might be involved in is the differentiation process of neurons. Scientists have found that when the ligand, STI1 (secreted from astrocytes) binds a receptor on the cellular prion glycoprotein membrane, the neurons differentiate. There were much lower levels of neurogenesis in neuron-astrocyte co-cultures, when they did not express the Prnp gene. Furthermore, they suggested that the interaction between cellular prion proteins and STI1 may play a role in protecting against apoptosis, as they have seen in neurons located in the hippocampus and the retina8 . It is likely that there are other molecular factors in ...
Cellular prion protein, a membrane protein, is expressed in all mammals. Prion protein is also found in human blood as an anchorless protein, and this protein form is one of the many potential sources of misfolded prion protein replication during transmission. Many studies have suggested that β-amyloid1-42 oligomer causes neurotoxicity associated with Alzheimers disease, which is mediated by the prion protein that acts as a receptor and regulates the hippocampal potentiation. The prevention of the binding of these proteins has been proposed as a possible preventative treatment for Alzheimers disease; therefore, a greater understanding of the binding hot-spots between the two molecules is necessary. In this study, the epitope mapping immunoassay was employed to characterize binding epitopes within the prion protein and complementary epitopes in β-amyloid. Residues 23-39 and 93-119 in the prion protein were involved in binding to β-amyloid1-40 and 1-42, and monomers of this protein interacted ...
1B10: Solution structure of a 142-residue recombinant prion protein corresponding to the infectious fragment of the scrapie isoform.
... This paper describes the results of tests using conventional triaxial apparatus with loading and unloading, on samples of medium sand with two different unit weights. The method is used to study the elastic and plastic volumetric and axial strains under the conditions of hydrostatic and deviator stress. It is shown that under hydrostatic compression, the elastic volumetric strain of medium sand is always greater than its plastic volumetric strain. The ratio of elastic volumetric strain to plastic volumetric strain may decrease as the hydrostatic pressure increases. Other conclusions are also described.
Close The Infona portal uses cookies, i.e. strings of text saved by a browser on the users device. The portal can access those files and use them to remember the users data, such as their chosen settings (screen view, interface language, etc.), or their login data. By using the Infona portal the user accepts automatic saving and using this information for portal operation purposes. More information on the subject can be found in the Privacy Policy and Terms of Service. By closing this window the user confirms that they have read the information on cookie usage, and they accept the privacy policy and the way cookies are used by the portal. You can change the cookie settings in your browser. ...
Technology Networks is an internationally recognised publisher that provides access to the latest scientific news, products, research, videos and posters.
Huntingtons and Parkinsons diseases are neurodegenerative disorders associated with unusual protein interactions. Although the origin and evolution of these diseases are completely different, characteristic deposits of protein aggregates (huntingti
Activation of phospholipase A2 (PLA2) and the subsequent metabolism of arachidonic acid (AA) to prostaglandins have been shown to play an important role in neuronal death in neurodegenerative disease. Here we report the effects of the prion peptide fragment HuPrP106-126 on the PLA2 cascade in primary cortical neurons and translocation of cPLA2 to neurites. Exposure of primary cortical neurons to HuPrP106-126 increased the levels of phosphorylated cPLA2 and caused phosphorylated cPLA2 to relocate from the cell body to the cellular neurite in a PrP-dependent manner, a previously unreported observation. HuPrP106-126 also induced significant AA release, an indicator of cPLA2 activation; this preceded synapse damage and subsequent cellular death. The novel translocation of p-cPLA2 postulated the potential for exposure to HuPrP106-126 to result in a re-arrangement of the cellular cytoskeleton. However p-cPLA2 did not colocalise significantly with F-actin, intermediate filaments, or microtubule-associated
A proposal by Dr. Harlan Caldwell at the Rocky Mountain Laboratories (RML) involving the deliberate transfer of a tetracycline resistance trait to non-ocular strains of Chlamydia trachomatis has been submitted to the NIH Office of Biotechnology Activities (OBA). The introduction of tetracycline...
Here, we report the development and further characterisation of a novel PrP-specific monoclonal antibody: 2A11. By Western blot analysis, 2A11 reacts with PrPC from a variety of species including cow, sheep, pig, hamster, rabbit, cat, dog, deer and mouse but fails to react with human, chicken and turtle PrP. Reactivity to PrPC in Western blot was found to be dependent on the redox state of the protein since binding of mAb 2A11 to its epitope was more effective in reducing conditions. 2A11 binding site was mapped within a region comprised by residues 171-179 (six octarepeats bovine PrP notation; 163-171 for the ovine PrP notation). Interestingly, in immunohistochemistry (IHC) analysis, immunoreactivity was greatly enhanced after proteinase K (PK) sample treatment, while little or no reaction was observed in non-PK-treated BSE samples and samples from healthy animals. Quantitative differences in reactivity to BSE prions after PK treatment were also observed, to a lesser extent, by Western blot ...
While prions can be thought of like a disease, that is not a good description. Prions are just misfolded proteins, that can make similar proteins misfold as well.. To understand what this means, proteins can be compared to hundreds of springs attached together in a large blanket of springs. Some of the springs are extension springs, and some are contraction springs. To execute its function, a protein will fold up this blanket of springs into a ball.. And it will fold up exactly the same way every time.. But a prion is a mistake in the folding up process. If it folds up incorrectly, the protein does not work. And to make matters worse, it can "tell" other proteins of its type to fold up incorrectly as well.. Importantly, priors happen constantly in our bodies, and just as constantly, they are destroyed by our bodies. But infectious prions are not *recognized* as prions by our bodies, so they are not destroyed, and can try to tell all the other proteins like them to misfold as well. And once you ...
WEDNESDAY, MAY 17, 2017 CWD, TSE, PRION, Cattle, Pigs, Sheep, and Humans aka Mad Cow Disease http://chronic-wasting-disease.blogspot.com/2017/05/cwd-tse-prion-cattle-pigs-sheep-and.html kind regards, terry
The demonstration of prion secretion in sheep in a variety of matrices including milk (Maddison et al. (2009) J. Virol. 83:8293-8296), saliva (Maddison et al. (2010) J. Inf. Dis. 201:1672-1676.) and faeces (Terry et al. (2011) Vet. Res. 42:65). Excretion/secretion occurs through long asymptomatic periods of disease development and from sheep with a range of PRNP genotypes, including those with limited lymphoreticular involvement in prion replication (Gough et al. (2011) J. Virol. 86:566-571 ...
Mechanism of PrP-mediated myopathy. Accumulation of an N-terminal truncated PrP C1 fragment in muscle activates p53 resulting in the induction of p53-regulated
For example, people use terms like ввdirectionality,вв ввblobbiness,вв ввrandomness,вв and so on. System suitability в resolution minimum of 5.
In a new study NYU School of Medicine researchers report that they have found several chemical compounds, including an antidepressant, that have powerful effects against brain-destroying prion infections in mice, opening ...
Meme (rhymes with team) is a pretty vague term. As it is commonly used, it means a viral idea, one that is replicated in new hosts by contact with the original and/or another carrier. The term was coined by Richard Dawkins in The Selfish Gene, to describe a self-propagating unit of cultural information. Religions, for example, are meta-memes, giant conglomerations of ideas and information transmitted through entire populations across millenia. Livejournal quizzes and internet 5p33,,, in fact most transmitted ideas, can be considered as memes with differing levels of virulence ...
pep:known chromosome:VEGA66:2:131909928:131938429:1 gene:OTTMUSG00000014846 transcript:OTTMUST00000035259 gene_biotype:protein_coding transcript_biotype:protein_coding gene_symbol:Prnp description:prion protein ...
The study results, reported by NIH scientists at the National Institute of Allergy and Infectious Diseases (NIAID), are similar to findings from two newly reported human cases of the prion disease Gerstmann-Straussler-Scheinker syndrome (GSS). This finding represents a new mechanism of prion disease brain damage, according to study author Bruce Chesebro, M.D., chief of the Laboratory of Persistent Viral Diseases at NIAIDs Rocky Mountain Laboratories.. Prion diseases, also known as transmissible spongiform encephalopathies, primarily damage the brain. Prion diseases include mad cow disease or bovine spongiform encephalopathy in cattle; scrapie in sheep; sporadic Creutzfeldt-Jakob disease (CJD), variant CJD and GSS in humans; and chronic wasting disease in deer, elk and moose.. The role of a specific cell anchor for prion protein is at the crux of the NIAID study. Normal prion protein uses a specific molecule, glycophosphoinositol (GPI), to fasten to host cells in the brain and other organs. In ...
Human prion diseases are fatal neurodegenerative disorders that include Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker disease, fatal familial insomnia, kuru and variant CJD (vCJD; Collinge 2001, 2005; Wadsworth & Collinge 2007). Their central feature is the post-translational conversion of host-encoded, cellular prion protein (PrPC) to an abnormal isoform, designated PrPSc (Prusiner 1982; Collinge 2001). Substantial evidence indicates that an abnormal PrP isoform is the principal, if not the sole, component of the transmissible infectious agent, or prion (Prusiner 1982; Collinge 2001; Weissmann 2004; Collinge & Clarke 2007). Human prion diseases are biologically unique in that the disease process can be triggered through inherited germ line mutations in the human prion protein gene (PRNP), infection (by inoculation, or in some cases by dietary exposure) with prion-infected tissue or by rare sporadic events that generate PrPSc (Collinge 2001, 2005; Wadsworth et al. 2003; ...
TY - JOUR. T1 - Gerstmann-straussler-scheinker disease (Prnp p102l). T2 - Amyloid deposits are best recognized by antibodies directed to epitopes in prp region 90-165. AU - Piccardo, Pedro. AU - Ghetti, Bernardino. AU - Dickson, Dennis W.. AU - Vinters, Harry V.. AU - Giaccone, Giorgio. AU - Bugiani, Orso. AU - Tagliavini, Fabrizio. AU - Young, Katherine. AU - Dlouhy, Stephen R.. AU - Seiler, Charles. AU - Jones, Carrie K.. AU - Lazzarini, Alice. AU - Golbe, Lawrence I.. AU - Zimmerman, Thomas R.. AU - Perlman, Susan L.. AU - McLachlan, Donald C.. AU - George-Hyslop, Peter H St. AU - Lennox, Anne. PY - 1995. Y1 - 1995. N2 - Gerstmann-Straussler-Scheinker (GSS) disease is a familial neurological disorder pathologically characterized by accumulation of prion protein (PrP) in the form of fibrillary and non-fibrillary deposits within the cerebrum and cerebellum. We have studied two patients in whom the disease is caused by a leucine for proline amino acid substitution at residue 102 of PrP. In both ...
Interpretive Summary: The transmissible spongiform encephalopathies (also called prion diseases) are fatal neurodegenerative diseases that affect animals and humans. The agent of prion diseases is a misfolded form of the prion protein that is resistant to breakdown by the host cells. Since all mammals express prion protein on the surface of various cells such as neurons, all mammals are, in theory, capable of replicating prion diseases. One example of a prion disease, bovine spongiform encephalopathy (BSE; also called mad cow disease), has been shown to infect cattle, sheep, exotic undulates, cats, non-human primates, and humans when the new host is exposed to feeds or foods contaminated with the disease agent. The purpose of this study was to test whether non-human primates (cynomologous macaque) are susceptible to the agent of sheep scrapie. After an incubation period of approximately 10 years a macaque developed progressive clinical signs suggestive of neurologic disease. Upon postmortem ...
The amyloidotic form of bovine spongiform encephalopathy (BSE) termed BASE is caused by a prion strain whose biological properties differ from those of typical BSE, resulting in a clinically and pathologically distinct phenotype. Whether peripheral tissues of BASE-affected cattle contain infectivity is unknown. This is a critical issue since the BASE prion is readily transmissible to a variety of hosts including primates, suggesting that humans may be susceptible. We carried out bioassays in transgenic mice overexpressing bovine PrP (Tgbov XV) and found infectivity in a variety of skeletal muscles from cattle with natural and experimental BASE. Noteworthy, all BASE muscles used for inoculation transmitted disease, although the attack rate differed between experimental and natural cases (~70% versus ~10%, respectively). This difference was likely related to different prion titers, possibly due to different stages of disease in the two conditions, i.e. terminal stage in experimental BASE and ...
bovine spongiform encephalopathy - Find news stories, facts, pictures and video about bovine spongiform encephalopathy - Page 1 | Newser
Bovine spongiform encephalopathy (BSE) belongs to a group of fatal prion diseases that result from the misfolding of the cellular prion protein (PrPC) into a pathogenic form (PrPSc) that accumulates in the brain. In vitro assays such as serial protein misfolding amplification and real-time quaking-induced conversion (RT-QuIC) allow assessment of the conversion of PrPC to PrPSc. RT-QuIC can be used for the detection of prions in a variety of biological tissues from humans and animals. However, there is no such comparison of RT-QuIC data between BSE positive and presymptomatic cattle. Further, the current study assesses prion distribution in multiple brain regions of clinically ill or subclinical animals. Here, we compare RT-QuIC reactions seeded with brain samples collected from experimentally inoculated cattle that were clinically ill or subclinically affected with BSE. The results demonstrate RT-QuIC seeding in various brain regions of an animal with subclinical BSE despite being determined ...
The occurrence of multiple strains of prions may reflect conformational variability of PrPSc, a disease-associated, aggregated variant of the cellular prion protein, PrPC. 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 scrapie, chronic wasting disease (CWD), bovine spongiform encephalopathy (BSE), and mouse-adapted Rocky Mountain Laboratory scrapie prions. Furthermore, using LCPs we differentiated between field isolates of BSE and bovine amyloidotic spongiform encephalopathy, and identified noncongophilic deposits in prion-infected deer and sheep. We found that fibrils with distinct morphologies generated from chemically identical recombinant PrP yielded unique LCP spectra, suggesting that spectral characteristic differences ...
The majority of bovine spongiform encephalopathy (BSE) cases have been ascribed to the classical form of the disease. H-type and L-type BSE cases have atypical molecular profiles compared to classical BSE and are thought to arise spontaneously. However, one case of H-type BSE was associated with a heritable E211K mutation in the prion protein gene. The purpose of this study was to describe transmission of this unique isolate of H-type BSE when inoculated into a calf of the same genotype by the intracranial route. Electroretinograms were used to demonstrate preclinical deficits in retinal function, and optical coherence tomography was used to demonstrate an antemortem decrease in retinal thickness. The calf rapidly progressed to clinical disease (9.4 months) and was necropsied. Widespread distribution of abnormal prion protein was demonstrated within neural tissues by western blot and immunohistochemistry. While this isolate is categorized as BSE-H due to a higher molecular mass of the unglycosylated
Transmissible spongiform encephalopathies (TSEs) are neurodegenerative diseases that affect several mammalian species. At least three factors related to the host prion protein are known to modulate susceptibility or resistance to a TSE: amino acid sequence, atypical number of octapeptide repeats, and expression level. These factors have been extensively studied in breeds of Bos taurus cattle in relation to classical bovine spongiform encephalopathy (BSE). However, little is currently known about these factors in Bos indicus purebred or B. indicus × B. taurus composite cattle. The goal of our study was to establish the frequency of markers associated with enhanced susceptibility or resistance to classical BSE in B. indicus purebred and composite cattle. No novel or TSE-associated PRNP-encoded amino acid polymorphisms were observed for B. indicus purebred and composite cattle, and all had the typical number of octapeptide repeats. However, differences were observed in the frequencies of the 23-bp and 12
This category includes disorders caused by prions, which are infectious proteins. Examples of the transmissible spongiform encephalopathies they cause include Creutzfeldt-Jakob Syndrome, Bovine Spongiform Encephalopathy, Gerstmann-Straussler-Scheinker Disease, Kuru, Scrapie in sheep and goats, Chronic Wasting Disease of cervids, Transmissible Mink Encephalopathy, and Fatal Familial Insomnia.
IMPORTANCE: The diagnosis of autoimmune and neurodegenerative conditions can be unclear. Treatments such as removing the associated tumor, if present, and immunosuppression can halt or often reverse the progression of autoimmune conditions, but there is no curative treatment for neurodegenerative conditions. The presence of autoantibodies can sometimes be misleading. This report illustrates potential difficulties in differentiating autoimmune encephalopathies from sporadic Creutzfeldt-Jakob disease. OBSERVATIONS: In a clinical follow-up of an older man with rapidly evolving encephalopathy at a neuroscience center, unsuccessful treatment with immunosuppression based on the incorrect presumptive diagnosis of Morvan syndrome was followed by the correct histological diagnosis of sporadic Creutzfeldt-Jakob disease. CONCLUSIONS AND RELEVANCE: Autoimmune encephalopathies raise important treatment options and potential for recovery. However, since neuronal antibodies may be positive in prion disease,
Prions are misfolded proteins that propagate by corrupting properly folded versions of themselves. The prion protein PrP (known as PrPSC in its misfolded form) causes deadly transmissible spongiform encephalopathies, including bovine spongiform encephalopathy (BSE) in cows, scrapie in sheep, and Creutzfeldt-Jakob disease (CJD) in humans. PrPSC molecules attach to and convert normal PrP proteins into the toxic form, accelerating the formation of PrPSC aggregates and fibrils. When these aggregates break apart, each fragment becomes a seed that can corrupt new PrP molecules. This break-up process is what senior author Adriano Aguzzi of the University of Zurich aimed to target. "That is the most important moment in the life of a prion fibril, just like mitosis is for a cancer cell," Aguzzi told Alzforum. As his weapon of choice, Aguzzi chose a group of compounds already known for their amyloid-smothering properties. Luminescent conjugated polythiophenes (LCPs) are fluorescent molecules that ...
Sporadic Creutzfeldt-Jakob disease (sCJD) is the commonest form of human prion diseases, accounting for about 85% of all cases. Current criteria for intra vitam diagnosis include a distinct phenotype, periodic sharp and slow-wave complexes at electroencephalography (EEG), and a positive 14-3-3-protein assay in the cerebrospinal fluid (CSF). In sCJD, the disease phenotype may vary, depending upon the genotype at codon 129 of the prion protein gene (PRNP), a site of a common methionine/valine polymorphism, and two distinct conformers of the pathological prion protein. Based on the combination of these molecular determinants, six different sCJD subtypes are recognized, each with distinctive clinical and pathologic phenotypes. We analyzed CSF samples from 127 subjects with definite sCJD to assess the diagnostic value of 14-3-3 protein, total tau protein, phosphorylated181 tau, and amyloid beta (Aβ) peptide 1-42, either alone or in combination. While the 14-3-3 assay and tau protein levels were the most