Dissertations / Theses on the topic 'Prions'
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Sang, Chieh. "Single molecule fluorescence studies of prions and prion-like proteins." Thesis, University of Cambridge, 2019. https://www.repository.cam.ac.uk/handle/1810/287929.
Full textApodaca, Jennifer J. "Regulation of prion protein in yeast and mammalian cells via ubiquitin mediated degradation a dissertation /." San Antonio : UTHSC, 2008. http://proquest.umi.com.libproxy.uthscsa.edu/pqdweb?did=1594496391&sid=6&Fmt=2&clientId=70986&RQT=309&VName=PQD.
Full textUrrea, Zazurca Laura. "Funciones de la proteína priónica celular, alfa-sinucleína y reelina en enfermedades neurodegenerativas." Doctoral thesis, Universitat de Barcelona, 2018. http://hdl.handle.net/10803/482168.
Full textMany neurodegenerative diseases are characterized by the loss of neurons and intracellular accumulation of abnormal proteins, with the formation of inclusion bodies. Parkinson’s disease (PD) is the second most common form of neurodegenerative diseases. PD shows an abnormal accumulation of α-synuclein aggregates in neurons, called Lewy bodies (LB). Several groups have reported that abnormal form of α-synuclein can propagate through the cells and, consequently, form inclusions. Thus, it has been suggested different molecular mechanisms involved in α-synuclein propagation. It has been reported that cellular prion protein (PrPc) is a receptor of β-amyloid. In this study, we analyse whether the PrPc is a receptor for α-synuclein. Animals with different PrPc expression were intracranially injected with α-synuclein protofibrils. We observe that PrPc expression is not mandatory for α-synuclein propagation, but PrPc-overexpressing mice show more aggregates than in PrPc absence. Moreover, charge cluster domain of PrPc is essential for α-synuclein binding. In addition, we study Reelin levels in different neurodegenerative diseases. Reelin is a glycoprotein that is crucial for the correct cytoarchitectonic organization of the developing Central Nervous System. Decreased levels of Reelin lead to synaptic dysfunction or neurodegeneration. In the present study, we analyse the changes in Reelin and Reln mRNA in Alzheimer’s disease, Dementia with Lewy Bodies (DLB), Parkinson´s disease (PD) and sporadic Creutzfeldt-Jakob disease (sCJD). Meanwhile, inmunoblot results indicate decreased levels of Reelin in AD and DLB, PD do not show changes. In contrast, it has been detected an increase in sCJD(I). Reelin increased levels depends on reactive oxygen species (ROS). Using inhibitors of ROS production, as DPI and NAC, Reelin levels are maintained.
Peoc'h, Katell. "La protéine << prion-like >> Doppel humaine : caractérisation et relation avec la protéine prion." Paris 5, 2003. http://www.theses.fr/2003PA05N096.
Full textPrion are infectious agents accumulating in the central nervous system, constituted of PrPsc the modified isoform of the prion protein (PrPc), encoded by the PRNP gene. The Doppel protein (Dpl) is encoded by the PRND gene nearby PRNP. Four Polymorphisms of PRND are observed in human ; none of them modify the susceptibility to prion diseases. Prnd expression remains unchanged after infection in neuroblastoma cells. Dpl surexpression do not change the PrPsc accumulation in these cells and the cerebral accumulation of Dpl is not modified in patients with Cretzfeld-Jakob disease. Dpl in humans is so expressed both on germinal and somatic cells in the male genital tract, suggesting its implication in fertility. Sperm cells could make a good tool to investigate the interaction between Dpl and PrP wich are both. .
Peyrin, Jean-Michel. "Implication des cellules microgliales dans la neuropathologie des maladies à prions." Paris 5, 1998. http://www.theses.fr/1998PA05P226.
Full textBariar, Bhawana. "Effects of the components of the Get pathway on prion propagation." Thesis, Atlanta, Ga. : Georgia Institute of Technology, 2007. http://hdl.handle.net/1853/26659.
Full textCommittee Chair: Chernoff,Yury; Committee Member: Cairney,John; Committee Member: Choi,Jung; Committee Member: Doyle,Donald; Committee Member: Lobachev,Kirill. Part of the SMARTech Electronic Thesis and Dissertation Collection.
Bamia, Aline. "Identification de nouvelles molécules anti-prions et caractérisation de leurs modes d'action." Thesis, Brest, 2019. http://www.theses.fr/2019BRES0047.
Full textPrion is infectious protein responsible of neurodegenerative diseases in human and animal. Scrapie in goat and sheep and Creutzfeldt-Jakob disease in human are prion-related diseases. Prion diseases are fatal and to date there is no efficient treatment against these troubles. This is why in our lab we focus on identification of new compounds efficient against prions. Flunarizine was identified as new anti-prion compound efficient against yeast prion [PSI+] and [URE3], and against mammalian prion PrPSc in vitro, ex vivo and in vivo. Flunarizine may be good drug candidate against prion diseases due to its anti-prion potential in different model. Structure-activity relationship (SAR) around flunarizine hightlights 31 compounds out of 47 which inhibit prion PrPSc propagation in vitro. Six of most efficient compounds cleared prion PrPSc in organotypic slice culture. There were no relationship between flunarizine and related compound activities against prion PrPSc and their known mode of action. The most potent compounds against PrPSc inhibit PFAR (protein folding activity of ribosome). PFAR is a protein chaperon activity which is involved in yeast prion [PSI+] propagation. Many tested compounds are good candidates for drugs repurposing against prion diseases because of their important activity against PrPSc prion.Inhibition of PFAR by all the hightly effective flunarizine related compounds, suggest that PFAR may be consider as cellular target for prion related-diseases treatment
Heiseke, Andreas. "Prions and autophagy: Effect of lithium on prion infection and role of basal autophagy in primary prion infection." kostenfrei, 2010. https://mediatum2.ub.tum.de/node?id=818228.
Full textKrejciova, Zuzana. "Exposure and response of human non-neuronal cells to prions in vitro." Thesis, University of Edinburgh, 2012. http://hdl.handle.net/1842/8186.
Full textChu, Clement SM. "Towards the structure of yeast prions." Diss., Search in ProQuest Dissertations & Theses. UC Only, 2009. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3390039.
Full textRagagnin, Audrey. "Mort neuronale et maladies à prions." Thesis, Strasbourg, 2014. http://www.theses.fr/2014STRAJ094/document.
Full textThe conversion of the protective cellular prion protein PrPC into an infectious, neurotoxic conformer PrPSc is a feature of prion diseases. In the prion-diseased brain, the loss of PrPC, the production of pathogenic PrPSc and inflammation contribute to neuronal death by still unknown mechanisms.The present results validate cerebellar organotypic cultures as a valuable experimental system to study ex vivo these mechanisms and provide insight into the apoptotic and autophagic processes activated by the absence of PrPC in Prnp-deficient mice and by PrPSc prions and lead to the death of the cerebellar Purkinje cells. A second line of research in situ showed that the anatomo-functional compartmentation of the mouse cerebellum is an endogenous parameter of the pathogenesis of the 22L scrapie prions. Finally, another in situ approach revealed that prions increase the levels of TNFR1, a receptor for the pro-inflammatory cytokine TNF-α at the membrane of the astrocytes enveloping Purkinje cell excitatory synapses in the cerebellar cortex of infected mice. This implies that the response of synaptic complexes to prions involves a glial component
Gierusz, Leszek A. "Folding and fibril formation of prions." Thesis, University of Warwick, 2012. http://wrap.warwick.ac.uk/56927/.
Full textToupet, Karine. "Stratégies thérapeutiques des maladies à prions." Montpellier 2, 2009. http://www.theses.fr/2009MON20128.
Full textPrion diseases are fatal neurodegenerative disorders that affect both humans and animals. These diseases are induced by the accumulation in the brain of the misfolded isoform of the normal cellular prion protein: PrPSc. The emergence of new risks of transmission for these diseases and the lack of efficient treatments, prompt us to search for new therapeutic strategies and targets. We developed two innovative therapeutic approaches. The first one consisted in searching for molecules able to trap preamyloid forms of PrPSc (dimers and trimers), known as key elements in the replication cycle of prions. A drugs screening approach, in silico and in cellulo, allowed us to discover thienyl pyrimidine and thienyl azine compounds able to specifically oligomerize PrPSc molecules. These PrPSc oligomers decrease prions infectivity in vivo, highlighting the therapeutic potential of these compounds. Our second strategie is a gene therapy approach using the dominant negative properties of certain polymorphisms of the prion protein, such as the Q218K and Q167R mutants. Our objective was to evaluate the therapeutic potential of lentiviral vectors carrying the PrPQ218K and PrPQ167R mutants, in mice, at the terminal stage of the disease. We succeeded in significantly prolonging the survival time of mice of 20%, with two intracerebrally chronic injections of lentiviral vectors carrying the PrPQ167R mutant. All our results not only open the way for new therapeutic strategies against prion diseases but also will benefit for therapies of other neurodegenerative disorders
Ekwa, Robert. "Les maladies à prions : problèmes épistémologiques." Paris 1, 2012. http://docelec.u-bordeaux.fr/login?url=http://www.harmatheque.com/ebook/les-maladies-a-prions--problemes-epistemologiques--volume-2--vache-folle-et-raisonnements-causals-41085.
Full textChen, Buxin. "Prion species barrier at the short phylogenetic distances in the yeast model." Diss., Atlanta, Ga. : Georgia Institute of Technology, 2008. http://hdl.handle.net/1853/29762.
Full textCommittee Chair: Chernoff, Yury; Committee Member: Bommarius, Andreas; Committee Member: Doyle, Donald; Committee Member: Lobachev, Kirill; Committee Member: Yi, Soojin. Part of the SMARTech Electronic Thesis and Dissertation Collection.
Grégoire, Sylvie. "Etude de la réponse immune contre la protéine du prion : perspectives thérapeutiques." Paris 5, 2004. http://www.theses.fr/2004PA05N081.
Full textTSE are lethal neurodégénérative disorders. Some works showed that we could generate a relative immunity response against prion protein (PrP), the major or unique cause of the disease. This work permit to highlight immun peptides from the PrP. First, three peptides were identified, in PrP KO mice, for their capacité to induce T p143-172, p158--187 and B p98-127 immun responses. Second, these peptides were tested with the same immun protocol in PrP+ mice, but none gave a delectable immun response. Yet, a response could be obtained with these peptides by immunization with oligo-CpG. Finally, peptide p158-187 was validated for its immunprotective capacity during the lymphoinvasion phase, in mouse experimental scrapie. But some evidences of brain infiltrats could let think of a possible autoimmun reaction
Wang, Weiqiang. "Prion inspired nanomaterials and their biomedical applications." Doctoral thesis, Universitat Autònoma de Barcelona, 2020. http://hdl.handle.net/10803/670982.
Full textLos amiloides muestran una estructura fibrilar altamente ordenada. Muchos de estos ensamblajes aparecen asociados a enfermedades humanas. No obstante, la naturaleza controlable, estable, modulable y robusta de las fibras amiloides se puede emplear para construir nanomateriales notables con una amplia gama de aplicaciones. Los priones funcionales constituyen una clase particular de amiloides. Estas proteínas transmisibles exhiben una arquitectura modular, con un dominio priónico desordenado responsable del ensamblaje y uno o más dominios globulares que dan cuenta de la actividad. Cabe destacar que la proteína globular original se puede reemplazar con cualquier proteína de interés sin comprometer el potencial de fibrilación. Estas fusiones genéticas forman fibrillas en las que el dominio globular permanece plegado, lo que genera nanoestructuras funcionales. Sin embargo, en muchos casos, el impedimento estérico restringe la actividad de estas fibrillas. Esta limitación puede resolverse diseccionando los dominios de priones en secuencias más cortas que mantengan sus propiedades de autoensamblado mientras permiten un mejor acceso a la proteína en el estado fibrilar. En esta tesis doctoral, exploramos el "soft amyloid core" (SAC) del prion de levadura Sup35p como una unidad modular de autoensamblaje, que recapitula la propensión a la agregación del dominio priónico completo. Fusionamos el SAC con diferentes proteínas globulares de interés que difieren en conformación y tamaños, creando un enfoque genético general y directo para generar nanofibrillas dotadas de las funcionalidades deseadas. El modelado computacional nos permitió obtener información sobre la relación entre el tamaño de los dominios globulares y la longitud del conector que los une con el SAC, proporcionando la base para el diseño de nanomateriales con diferentes propiedades mesoscópicas, ya sean nanofibrillas o nanopartículas. Sobre esta base, diseñamos y producimos, por primera vez, nanopartículas amiloides esféricas, altamente activas, no tóxicas, de tamaño definido, y diseñamos nanoestructuras bifuncionales con aplicación en la administración dirigida de fármacos. Las lecciones aprendidas en estos ejercicios permitieron la construcción de una nanofibrilla similar a un anticuerpo biespecífico con potencial para su uso en inmunoterapia. En resumen, los nanomateriales funcionales similares a los priones descritos aquí aprovechan la metodología de fusión genética para generar un nuevo conjunto de estructuras con aplicación en biomedicina y biotecnología.
Amyloids display a highly ordered fibrillar structure. Many of these assemblies appear associated with human disease. However, the controllable, stable, tunable, and robust nature of amyloid fibrils can be exploited to build up remarkable nanomaterials with a wide range of applications. Functional prions constitute a particular class of amyloids. These transmissible proteins exhibit a modular architecture, with a disordered prion domain responsible for the assembly and one or more globular domains that account for the activity. Importantly, the original globular protein can be replaced with any protein of interest, without compromising the fibrillation potential. These genetic fusions form fibrils in which the globular domain remains folded, rendering functional nanostructures. However, in many cases, steric hindrance restricts the activity of these fibrils. This limitation can be solved by dissecting prion domains into shorter sequences that keep their self-assembling properties while allowing better access to the protein in the fibrillar state. In this PhD thesis, we exploited the "soft amyloid core (SAC)" of the Sup35p yeast prion as a modular self-assembling unit, which recapitulates the aggregation propensity of the complete prion domain. We fused the SAC to different globular proteins of interest differing in conformation and sizes, building up a general and straightforward genetic approach to generate nanofibrils endowed with desired functionalities. Computational modeling allowed us to gain insights into the relationship between the size of the globular domains and the length of the linker that connects them to the SAC, providing the basis for the design of nanomaterials with different mesoscopic properties, either nanofibrils or nanoparticles. On this basis, we designed and produced, for the first time, highly active, non-toxic, spherical amyloid nanoparticles of defined size and engineered bifunctional nanostructures with application in targeted drug delivery. The lessons learned in these exercises resulted in the construction of a bispecific antibody-like nanofibril, showing potential in immunotherapy. In summary, the prion-like functional nanomaterials described here take profit of the genetic fusion approach to render a novel set of structures with application in biomedicine and biotechnology.
Robinson, Philip John. "The folding, misfolding and aggregation of prions." Thesis, University of Warwick, 2009. http://wrap.warwick.ac.uk/2792/.
Full textGozalo, Claire. "Nouvelles approches thérapeutiques des maladies à prions." Paris 5, 2006. http://www.theses.fr/2006PA05P619.
Full textThe purpose of this project was to map out new therapeutical approaches for the treatment of prion diseases through the study of original molecules belonging to two of the most efficient therapeutical classes described to date. Following efficacy studies on cellular models in comparison with Pentosan Polysulfate, the reference molecule, CR36 was selected within the heparan-mimetic class. The very different efficiency and toxicity profiles observed on various animal models led us to investigate on their respective mechanism of action and to propose different hypothesis : a central role in their affinity for PrP and in their interaction with endogenous heparan sulfates would therefore be played by the sulfation degree of these molecules. The selected porphyrins only induced a mild decrease of splenic PrPres after administration to mice. Their oxidative properties were not found to be involved in their anti-prion activity and our results favor the hypothesis of a structural and destabilizing role of the cooordinating metal for PrP aggregates
Boudet-Devaud, François. "La protéine prion cellulaire : un relai de neurotoxicité commun aux protéines amyloïdes et aux nanoparticules Protective role of cellular prion protein against TNFα-mediated inlammation through TACE α-secretase PrPSc-induced PDK1 overactivation promotes the production of seedable Amyloid-β peptides in prion diseases Corruption of cellular prion protein signaling by titanium dioxide or carbon black nanoparticles promotes the accumulation of amyloid-β peptides." Thesis, Sorbonne Paris Cité, 2018. http://www.theses.fr/2018USPCB127.
Full textThe cellular prion protein (PrPC) is a protein mostly expressed at the plasma membrane of neurons. Its transconformation into the pathogenic prion PrPSc is at the root of prion diseases. It is clearly established that the PrPSc-induced neurodegeneration depends on the expression of PrPC in neurons and results from the corruption of PrPC function(s) by PrPSc. Unravelling the role of PrPC is thus a prerequisite to grasp neurodegeneration mechanisms in prion diseases. Part of my work shows that PrPC exerts a cytoprotective function against TNFalpha inflammatory cytokine. PrPC silencing in neurons (PrPnull-neurons) renders these cells highly sensitive to TNFalpha due to surface accumulation of TNFalpha receptor (TNFR). My work demonstrates that the loss of PrPC regulatory function on the clustering and signaling downstream of bêta 1 integrins in PrPnull neurons provokes the overactivation of the kinase PDK1, subsequent internalization of TACE alpha-secretase, and uncoupling of TACE from TNFR substrate. Because of the phenotypic proximity between PrPnull neurons (Ezpeleta et al. 2017) and PrPSc-infected neurons (Pietri et al. 2013; Alleaume-Butaux et al. 2015), my work supports the view of a loss of PrPC protective function in prion diseases. As concerns prion infection, my work shows that after PDK1 overactivation, internalized TACE is uncoupled from another substrate, the amyloid peptides precursor protein (APP), leading to the accumulation of neurotoxic peptides Abêta 40 and Abêta 42, hallmarks of Alzheimer's disease. Within a prion infectious context, Abêta 40/42 peptides are predominantly present as monomers, and to a lesser extent, as trimers and tetramers. By combining in vitro and in vivo approaches, we show that Abêta peptides produced by infected neurons do not alter replication nor the infectivity of prions. Nevertheless, we demonstrate that oligomerized Abêta is able to form amyloid plaques in the brain of transgenic APP23 mice infected by prions. In these mice, Abêta deposits accelerate prion pathogenesis. The last axis of my work deals with nanoparticles, that is, nanometric materials commonly found in manufactured products and industrial processes. My work shows that, as PrPSc and Abêta, titanium dioxide or carbon black assemblies interact with PrPC at the surface of neurons and deviate its signaling function, which leads, inter alia, to PDK1 overactivation, TACE internalization, TNFR accumulation at the plasma membrane, and neuronal cells hypersensitivity to TNFalpha inflammatory stress. We also found that nanoparticle-induced TACE uncoupling from APP increases Abêta peptide production by neurons. Even if no epidemiological study has demonstrated to date a link between nanoparticle exposure and Alzheimer's disease, my work suggests an causal implication of nanoparticles in the initiation or amplification of this disease
Gougerot, Alexianne. "Physiopathologie et thérapeutique des prions humains : une approche cellulaire." Thesis, Paris 6, 2017. http://www.theses.fr/2017PA066087/document.
Full textPrion diseases are fatal transmissible neurodegenerative disorders, with no effective treatment. Brain lesions include neuronal vacuolization, astrogliosis, neuronal loss and the accumulation of PrPSc, an abnormal isoform of the host-encoded cellular prion protein (PrPc). Some forms of prion diseases are associated with tau fibrillar pathology similar to that observed in Alzheimer’s disease except that Abeta peptides are replaced by PrPsc. Here we used a primary neuronal cultures to first explore the interplay between the formation of prion protein assemblies and the occurrence of tau pathology, and secondly to evaluate in vitro human strain propagation and the efficiency of some antiprion compounds towards human prions. We showed that tau hyperphosphorylation in response to recombinant PrPs exposition was mutation-dependent, conformation-dependent and varied with the PrPc expression level of exposed neurons. This effect was mediated by PDK1 kinase. We also demonstrated for the first time that human prion isolates could propagate in an in vitro model. This model was also useful to evaluate the efficacy of antiprion compounds that was further validated in vivo. Our results help us to better understand the amyloid protein-tau physiopathology interplay and provide a useful and unique tool for fast evaluation of therapeutic compounds active against human prion strains in a repositioning strategy in such rare but devastating diseases
Benoist, Catherine. "Précautions à prendre en milieu hospitalier, face aux prions." Paris 5, 1996. http://www.theses.fr/1996PA05P161.
Full textLenuzza, Natacha. "Modélisation de la réplications des Prions : Implication de la dépendance en taille des agrégats de PrP et de l'hétérogénéité des populations cellulaires." Phd thesis, Ecole Centrale Paris, 2009. http://tel.archives-ouvertes.fr/tel-00453321.
Full textDuarte, rodrigues Alysson. "Elaboration d'un dispositif de dépistage de maladies à prions." Thesis, Montpellier, Ecole nationale supérieure de chimie, 2015. http://www.theses.fr/2015ENCM0007.
Full textThe objective of this thesis was to develop a diagnostic device to prion diseases departing from the synthesis and functionalization of molecules having a high selectivity with the pathogenic form of the prion protein (PrPSc).In previous results, the Dr. Mike Robtizer's team has highlighted molecules that exhibit a strong affinity with the pathological form of the prion protein. The Western-Blot tests with contaminated brains homogenates treated with these compounds showed the formation of oligomeric forms (dimers and trimers) of the PrPSc only with contaminated samples. The identification of these oligomeric forms characterizes the sample as contaminated. The synthesized molecules represent a new family of compounds with a confirmed selectivity with the PrPSc.Among the synthesized molecules, one in particular has a pronounced affinity in the process of oligomerization of the pathological prion protein. This molecule, named MR100, has two 1,3,5-triazine-2,4-diamines functions coupled to a quaterthiophene spacer presents a high activity with the PrPSc.The tests with this molecule are still in the beginning (in partnership with INSERM - Unité 710 and EFS) and for this reason the improved synthesis of MR100 and the synthesis of new compounds carrying different chemical functions were developed in this doctoral thesis.The elaboration of the diagnostic device was made in two main steps. The first one was based on the synthesis of active molecules and its in vitro tests to verify their oligomeric-induced activity with PrPSc contaminated samples, inspired by the molecular approach developed in previous work.The active molecules have a high selectivity and specificity to the pathogenic forms of prion proteins and induce the formation of dimers and trimers of the PrPSc. The identification by Western Blot of these oligomeric forms characterizes the sample as contaminated.The second step was to select and graft the best candidates on solid supports to test their stability, reactivity and response in the same conditions
Bhamra, S. K. "Systematic mutagenesis of the mouse prion protein to identify critical regions for the efficient propagation of prions." Thesis, University College London (University of London), 2014. http://discovery.ucl.ac.uk/1443249/.
Full textSun, Meng. "Development of the new yeast-based assays for prion properties." Diss., Georgia Institute of Technology, 2011. http://hdl.handle.net/1853/45831.
Full textMercey, Raphaël. "Identification et caractérisation d'ARN ligands de la protéine prion." Tours, 2006. http://www.theses.fr/2006TOUR3311.
Full textOne of the unsolved problems in prion diseases relates to the physiological function of cellular prion protein (PrP), of which a misfolded isoform is probably the only component of the transmissible spongiform encephalopathies (TSE) agent. Knowledge of the PrP-binding molecules may help in elucidating its role and understanding the pathological events underlying prion diseases. Because nucleic acids are known to bind PrP, we used the SELEX approach to identify the preferred RNA sequences that bind to the ovine recombinant PrP. Our best RNA presents 21 nucleotides shared with a previously described PrP aptamer. We believe that the prion protein may have a physiological function related to nucleic acids presenting some of the patterns we identified in our study. Theses nucleic acids could be involved in the composition of the infectious agent. These RNA can be useful for diagnostic or as new tools to study prion diseases
Masel, Joanna. "The replication kinetics of prions and other amyloids." Thesis, University of Oxford, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.343422.
Full textHalfmann, Randal A. (Randal Arthur). "Discovery and characterization of prions in Saccharomyces cerevisiae." Thesis, Massachusetts Institute of Technology, 2011. http://hdl.handle.net/1721.1/62618.
Full textThis electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Cataloged from student-submitted PDF version of thesis. Vita.
Includes bibliographical references.
Some protein aggregates can perpetuate themselves in a self-templating protein-misfolding reaction. These aggregates, or prions, are the infectious agents behind diseases like Kuru and mad-cow disease. In yeast, however, prions act as epigenetic elements that confer heritable alternative phenotypes. Prion-forming proteins create bistable molecular systems whose semi-stochastic switching between functional states increases phenotypic diversity within cell populations. My thesis work explores the idea that rather than being detrimental, prions may commonly act to their host's advantage. To broaden the known range of prion phenomena in S. cerevisiae, I, together with a postdoctoral fellow in our lab, systematically surveyed the yeast proteome for prion-forming proteins. Using a combination of computational, cell biological, and biochemical approaches, we ultimately identified 18 novel prion domains capable of driving phenotypic switching, and an additional 6 domains that were highly positive for prion-like aggregation in other assays. These results establish the critical importance of intrinsic amyloid-forming tendencies for prion behavior by Q/N-rich proteins. We further confirmed that one of these proteins, the transcription factor Mot3, forms a novel prion in its endogenous context. An analysis of these findings revealed a strong and unexpected amino acid bias in prionogenic proteins: prions were strongly enriched for asparagine (N), but not the chemically related amino acid glutamine (Q). We validated this finding using molecular simulations and experimental analyses of Q-to-N and N-to-Q variants of prion domains. N-rich sequences had an intrinsic tendency to both nucleate and propagate amyloid conformers. Q-rich proteins tended instead to make structurally non-constrained interactions leading to proteotoxic soluble and non-amyloid aggregated conformers. The appendices include works in progress. Each explores a different aspect of prion biology. Appendix A confirms a theoretical prediction that prions, if functional, should preferentially regulate certain rapidly evolving genes. I demonstrate with the newly discovered prion protein, Mot3, that prions accelerate the appearance of new phenotypes in important traits like mating behavior and cell-adhesion. I further identify naturally occurring prion states of Mot3 and other prion proteins in wild yeast isolates, and show that elimination of these prions has strong phenotypic effects in these strains. Appendix B, work done in collaboration with another lab, establishes that Nup100, a GLFG nucleoporin, is a prion. The conformational flexibility of GLFG nucleoporins is critical for the function of the nuclear pore complex, a molecular sieve that regulates all macromolecular transport between the nucleus and cytoplasm.
by Randal A. Halfmann.
Ph.D.
D'Castro, L. M. "Biochemical and structural characterisation of infectious mammalian prions." Thesis, University College London (University of London), 2011. http://discovery.ucl.ac.uk/1310247/.
Full textSpeldewinde, Shaun. "Prions, autophagy, ageing and actin cytoskeleton in yeast." Thesis, University of Manchester, 2017. https://www.research.manchester.ac.uk/portal/en/theses/prions-autophagy-ageing-and-actin-cytoskeleton-in-yeast(03085d7f-283a-40e1-bcf7-d9533ff2e2fc).html.
Full textTalarek, Nicolas. "La conservation des mécanismes prions chez les ascomycètes." Bordeaux 2, 2004. http://www.theses.fr/2004BOR21154.
Full textPrion protein adopts two distinct conformations. One of them induces the conversion of the other one in a self-propagating manner. Prion proteins were identified in mammals (PrP) and microorganism as Saccharomyces cerevisiae (Ure2p and Sup35p) and Podospora anserina (HET-s). We ask whether mechanisms required for prion propagation are conserved thoughout the evolution. First we set up genetic tools for such studies in S. Paradoxus and S. Uvarum. These studies allow us to show that mechanism required for prion propagation are conserved and that prion properties are enciphered in amino acid sequence. We also showed that HET-s adopt a prion isoform in S. Cerevisiae and identified, during a collaboration, molecules that eliminate yeast and mammals prions
Ezpeleta, Juliette. "Du rôle physiologique de la protéine prion cellulaire à l'infection par les prions : régulation/dérégulation du module de signalisation PDK1/TACE α-secrétase Protective role of cellular prion protein against TNFα-mediated inflammation trough TACE α-secretase Cerebellar compartmentation of prion pathogenesis Production of seedable Amyloid-β peptides in prion diseases upon PrPSc-induced PDK1 overactivation." Thesis, Sorbonne Paris Cité, 2019. http://www.theses.fr/2019USPCB004.
Full textPrion diseases are neurodegenerative disorders characterized by the accumulation into the central nervous system of an abnormally folded protein called Scrapie prion protein (PrPSc). PrPSc is the transconformational isoform of a ubiquitous protein of the host named cellular prion protein (PrPC). It is well established that the toxicity of PrPSc is restricted to neurons and arise from a corruption of the physiological function(s) of PrPC. However, the mechanisms by which PrPSc exerts its neurotoxicity remain poorly understood, partly because the physiological function(s) of PrPC is/are still elusive. Currently, no one knows if PrPC loses a protective role or acquires a toxic function upon its conversion into PrPSc, a combination of both events is also possible. Identifying PrPC-associated function(s) is thus a prerequisite to understand how PrPSc provokes neurodegeneration. The present work reports for the first time a protective role of PrPC towards the pro-inflammatory cytokine sTNF-alpha-associated toxicity. We show that PrPC adjusts cell sensitivity to sTNF-alpha by controlling TACE-dependent TNFR1 shedding. Mecanistically, PrPC governs both (i) TACE activity, through PrPC coupling to NADPH oxidase/Reactive Oxygen Species production, and (ii) TACE localization, by downregulating the beta-1 integrins/ROCK/PDK1 signaling pathway, thus PrPC ensures the bioavailability of an active TACE at the plasma membrane. PrPC depletion provokes the micro-aggregation of beta-1 integrins, the overactivation of ROCK and PDK1 kinases, and the subsequent internalization of TACE into Caveolin-1 enriched micro-vesicles. This leads to a defect of TNFR1 shedding, which accumulates at the plasma membrane and renders PrPC-depleted neurons highly vulnerable to sTNF-alpha insult. These alterations have also been reported in prion-infected neurons with the same intensities, supporting the view that a loss-of-the protective function of PrPC towards sTNF-alpha likely occur along prion diseases. Within a prion infectious context, a collaborative work revealed that the cerebellar Purkinje cells that do not express zebrins are highly vulnerable to the toxicity of two prion strains, 22L and ME7, compared to Purkinje cells that express zebrins. This suggest a protective role of zebrins against PrPSc-associated toxicity. A major part of my thesis identifies a new target deregulated downstream from the PDK1/TACE signaling module, the amyloid precursor protein (APP), well-known for its implication in Alzheimer's disease. By abrogating the non-amyloidogenic cleavage of APP by TACE, PrPSc provokes the overproduction of Abeta40/42 peptides. Abeta40/42 predominates as monomers but are also found as multimeric assemblies, i.e. trimers and tetramers. PrPSc-induced Abeta40/42 overproduction relates to PDK1 overactivation as pharmacological inhibition of PDK1 attenuates production of Abeta monomers and renders multimers undetectable. Of note, our work reveals that Abeta peptides do not impact on PrPSc replication nor infectivity. Nevertheless, Abeta40/42 peptides generated upon prion infection can deposit in mice brains only if an exogenous Abeta seed is co-transmitted with PrPSc. Importantly, Abeta deposition leads to early death of prion-infected mice. This work delineates the conditions that allow Abeta plaques formation and highlights the onset of a mixed-pathology caused by the co-occurrence of PrPSc and Abeta deposition within a prion infectious context
Wegrzyn, Renee Diane. "Genetic, biochemical, and physiological study of yeast prion protein aggregation." Diss., Georgia Institute of Technology, 2003. http://hdl.handle.net/1853/25221.
Full textPremzl, Marko, and Premzl@anu edu au premzl@excite com Marko. "Prion Protein Gene and Its Shadow." The Australian National University. The John Curtin School of Medical Research, 2004. http://thesis.anu.edu.au./public/adt-ANU20050328.164529.
Full textBarros, Viegas Pedro José. "Expression et fonctions cellulaires couplées à la protéine prion PrPc au niveau de la barrière hemato-encéphalique." Paris 7, 2006. http://www.theses.fr/2006PA077018.
Full textThe prion protein PrPC is a GPI-anchored sialoglycoprotein, its conformational shift into the pathological form PrPSc being responsible for the prion diseases, transmissible fatal neurodegenerative encephalopathies that affect man (Creutzfeldt-Jakob disease, Fatal Familial Insomnia) and animals (scrapie, bovine spongiform encephalopathy). A number of progresses have been made regarding the implication of PrPSc in transmission and development of prion diseases. Nonetheless, the normal function of PrPC is still ill-defïned. We decided to study the expression and functions of PrPC in brain endothelial cells of the blood-brain barrier (BBB), a physiological barrier that protects the central nervous System and that constitutes a possible entry site for infectious prion. We have shown that PrPC is expressed at the intercellular junctions of brain endothelial cells of the BBB, at raft-like membrane microdomains. As for numerous adhesion molecules, its junctional localization is maintained by homophilic interactions between molecules in adjacent cells. We have also shown that PrPC, if not implicated in immune cell adhesion to the endothelium, is important for the transendothelial migration of monocytes. In addition, it should interact with the junctional proteins PECAM-1 through heparan sulfate proteoglycans. PrPC is also implicated in copper buffering at the cell membrane, and could completely abolish the copper- induced potentialization of cell death induced by homocystein. Taken together, these results show that PrPC is a junctional protein involved in transendotheliale migration and BBB integrity
Jaffré, Nina. "Découverte d'une nouvelle maladie neurologique au cours de l'étude du risque transfusionnel de la variante de la maladie de Creutzfeldt-Jakob dans le modèle expérimental du macaque cynomolgus (Macaca fascicularis)." Paris 7, 2014. http://www.theses.fr/2014PA077046.
Full textThe variant Creutzfeldt-Jakob disease (vCJD) is a prion disease caused by the transmission to humans o Bovine Spongiform Encephalopathy (BSE). Prion diseases imply the conversion of cellular prion protein (PrP) into a misfolded pathological isoform and its accumulation in the central nervous system (CNS). Among the 229 human cases of vCJD described, 3 were probably caused by secondary transmission through blood transfusion, raising concem about possible contamination through blood products from asymptomatic carriers. In order to evaluate this transfusional risk, we performed several exposures of cynon3olgus macaques to vCJD or BSE-infected blood components. Among them some developed classical vCJD, while many others exhibited an original neurological disease with spinal cord rather than cerebral lesions and apparent absence in the CNS of pathological PrP, major diagnostic marker of classical prion diseases. The goal of this thesis relies on the clinical, anatomopathological and biochemical characterization of these myelopathic cases exposed to prion-infected blood components in order to identify, if any, a similar disease in humans. The observation of a decrease in full-length cellular PrP in the spinal cord of these macaques implies the involvement of PrP in the pathogenesis of this disease. A complementary study in a murine transfusion model reproduces the previous observations and should help to better understand which blood components sustain the infectivity and how these blood components interact. In parallel the evaluation of the efficiency of a prion removal device to remove blood infectivity showed interesting results in cynomolgus macaques
Ayrolles-Torro, Adeline. "Etude du mécanisme d’action des composés thiényl-pyrimidines et azines sur les prions et leur valorisation potentielle dans un test diagnostic des ESST." Montpellier 2, 2009. http://www.theses.fr/2009MON20178.
Full textPrions diseases are fatal neurodegeneratives disorders, which affect both humans and animals. No early diagnosis test of prions as well as effective treatment exists. The infectious agent consists mainly of the abnormal form, named PrPSc of the cellular protein prion, PrPC. Even if the replication cycle of prions is not totally known, the majority of the therapeutic strategies target monomerics forms of PrPC, PrPSc as well as amyloid fibrils. Dimers or trimers of PrPSc were recently described and would be part of an unstable preamyloïde state. We hypothesize that the identification of small molecules interacting with those preamyloid intermediates would block the replication cycle of prions and thus would reduce their infectivity. For this purpose, we used an approach of virtual screening, followed by a cellular screening on prions infected-cells. We identified a family of thienyls pyrimidines and azines compounds, able of stabilizing dimers of PrPSc, and observable in denaturing conditions by immunoblot. In vivo studies indicate that the pre-incubation of compounds with infected brain homogenate, reduces the prion infectiosity of the inoculum, suggesting a potential therapeutic application. We also studied the mechanism of action of these molecules and we propose that these compounds could directly interact with prions via a mechanism of aggregation. We showed that thienyl pyrimidine compounds can discriminate the infected brain homogenates from healthy ones, by the presence of specific PrPSc dimers, suggesting a potential application for the development of a new diagnosis test for ESST
Chasseigneaux, Stéphanie. "Analyse moléculaire des interactions hôte-prions en systèmes cellulaires." Paris 5, 2006. http://www.theses.fr/2006PA05N20S.
Full textCGH array analysis of uninfected N2a sublines, susceptible or resistant to 22L prion strain, revealed chromosomal imbalances but did not demonstrate any characteristic profile of genomic alterations linked to phenotype. Likewise, sublines phenotype did not depend on the expression of Prnp nor PrPC. Analysis expression of a set of 29 genes revealed distinct transcriptional profiles in the N2a sublines. Transcriptional analysis of N2a5822L cells using microarrays demonstrated differential expression of genes implicated in transcription efficiency and cytoplasmic dynamics. Expression levels of a set of 38 genes in N2a5822L, in three susceptible sublines and in a resistant subline revealed diversity in transcriptional response to prion infection. Finally, study of PrPSc in a CJD patient harbouring the p. V180I mutation revealed the absence of the diglycosylated isoform supporting the evidence of the conversion of mono- and un-glycosylated mutated forms into the pathogenic mutant PrPSc180I
Cosseddu, Gian Mario. "Bases génétiques des neuropathologies à prions : le modèle ovin." Versailles-St Quentin en Yvelines, 2005. http://www.theses.fr/2005VERS0046.
Full textThe objective of this research project was to identify gènes affecting thé genetic sensibility/resistance to scrapie in sheep, outside thé PRNI gène. We dealt with this scientific problem following two complementary ways. First, we carried out a classical approach of positional clonin for Quantitative Trait Loci (QTL). We could thus identify a QTL on sheep chromosome 18 (OAR18), linked to thé TGLA122 and BM7243 markers. Subsequently, by thé targeted production of new microsatellites, we could confirm thé genetic association with thé QTL and significantly refine ils localisation into a ~7 Mb interval. In parallel with thé progresses of this genetic study, we developed a research program aiming at analysing thé modifications of gènes expression profiles caused by thé disease in thé brain, using thé Subtractive Suppressive Hybridization (SSH) technique. This way we identified six gènes influenced by thé development of thé disease, 5 of them are stimulated (CHN1, LRFN5, PPP2AC, CaMK2 and COX1 ) and another one is down-regulated (Rab9p40). In mice CHN1 is located at 74 M on chromosome 2 (MMU2), exactly in thé center of a QTL interval identified by Manolakou el al in 2001. LRFN5 is located at 40 Mb on HSA14, a position corresponding to thé interval previously identified on OAR18. Concerning CHN1, we could demonstrate thé existence ( an alternative splicing, responsible for two isoforms, one of which is specifically présent in affected brain
Guillerme, Florence. "Glycogénome et maladies à prions : étude d’une tremblante expérimentale." Limoges, 2006. https://aurore.unilim.fr/theses/nxfile/default/f18d1e1a-9a09-42e3-b978-dc64c7892673/blobholder:0/2006LIMO0069.pdf.
Full textPrion diseases are characterized by the accumulation of a pathologic isoform (PrPSc) of the cellular prion protein called PrPc. Prion is a GPI-anchored glycoprotein which interacts with various glycosylated partners, such as gangliosides. Analyses of glycogenome expression during an experimental scrapie disease lead us to identify an early alteration of expression of only two genes in scrapie-infected mice spleens: ST3GalV and Pigq. Both genes encode key enzymes implicated in GM3 and GPI anchor biosyntheses, respectively. Expression modifications occur long before the first clinical symptoms, induce a hyposialylation (notably at the membrane level) and probably lead to an increase of soluble prion proteins. Association of ST3GalV and Pigq down-regulations is thought to impair PrP transduction signal and to improve PrPSc spreading
Riemschoß, Katrin [Verfasser]. "Similarities of stress granules and cytosolic prions / Katrin Riemschoß." Bonn : Universitäts- und Landesbibliothek Bonn, 2019. http://d-nb.info/1206246170/34.
Full textKlingeborn, Mikael. "The prion protein in normal cells and disease : studies on the cellular processing of bovine PrPC and molecular characterization of the Nor98 prion /." Uppsala : Department of Molecular Biosciences, Swedish University of Agricultural Sciences, 2006. http://epsilon.slu.se/2006105.pdf.
Full textGug, Fabienne. "Nouveaux dérivés à activité anti-prion : synthèse d'outils moléculaires permettant l'étude de leur mécanisme d'action." Paris 5, 2006. http://www.theses.fr/2006PA05P631.
Full textTransmissible spongiform encephalopathies are a group of fatal neurodegenerative disorders characterized by the accumulation of an abnormal form of prion protein into aggregates in brain. There is currently no treatment available for these disorders. Recently a simple, safe and rapid yeast-based method to screen for anti-prion drugs had been developed by Pr M Blondel et al. Thanks to this method, two interesting compounds have been identified: 6-aminophenanthridine ( 6-AP) and 2,6-dichlorobenzylidene aminoguanidine (2,6-DBAG). This work is divided in two parts. In the first one, two original synthesis of 6-AP are presented and numerous series derived from 6-AP and 2,6-DBAG are described. Structure-activity relationships are discussed. In the second one, two types of new molecular tools derived from these two compounds are synthetised. Based on affinity chromatography and photoaffinity labelling these tools allowed the identification of the molecular targets of the active products
Anand, Ashish. "Development of a bio-sensing technique for the detection of prions in foods." Texas A&M University, 2003. http://hdl.handle.net/1969.1/1503.
Full textNako, Entela. "Using E. coli as an experimental system to study the behavior of prion-like proteins." Thesis, Harvard University, 2013. http://dissertations.umi.com/gsas.harvard:11065.
Full textWang, Kai. "Protéines infectieuses chez la levure Saccharomyces cerevisiae : un mal pour un bien ? Modulation de la propagation de prions de levure par le protéasome et les chaperons moléculaires durant la transition duauxique et la phase stationnaire." Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLS212/document.
Full text“Proteinaceous infectious particles”, or prions, are self-perpetuating alternate conformations of proteins that are responsible for heritable non-Mendelian traits in mammals, filamentous fungi and yeast. On a more general note, protein misfolding and aggregation is at the origin of over forty protein folding disorders including devastating neurodegenerative diseases such as Alzheimer’s, Parkinson’s or Huntington’s diseases. The aggregated proteins responsible for these diseases (i.e. amyloid-β peptide/tau, α-synuclein and huntingtin) were shown to propagate from cell to cell in a prion-like manner. The yeast Saccharomyces cerevisiae hosts many prion or prion-like proteins, unrelated in sequence and function, which proved to be excellent models for understanding the dynamics of prion aggregation and distribution upon cell division.Sup35p and Ure2p which cause the [PSI+] and [URE3] heritable traits, respectively, stand out as the most studied and best characterized yeast prions to date. A plethora of cellular factors, mostly belonging to various molecular chaperone families, were shown to affect yeast prion formation and propagation. Clearance of protein aggregates and prion particles is however poorly understood and documented. Our laboratory showed that the 26S proteasome degrades both the soluble and prion-associated fibrillar forms of Sup35p. In the first part of my thesis, we investigated the role of the 26S proteasome in the degradation of the soluble and fibrillar forms of Ure2p. We found that, as with Sup35p, the 26S proteasome is able to degrade the soluble native Ure2p, generating an array of amyloidogenic N-terminal peptides and a C-terminal fragment which is resistant to proteolysis. The N-terminal prion domain was shown to act as a degron required for proteasomal engagement and degradation. In contrast to Sup35p, fibrillar Ure2p resisted proteasomal degradation. We expect the structural variability within prion assemblies in a cellular context to dictate their interaction with proteolytic machineries in general and the proteasome in particular.The biology of yeast prions has been mostly explored in the context of logarithmically dividing cells. In nature however, most cells are generally in a post-mitotic non-dividing quiescent state. Yet little is known about the fate and properties of prion particles upon yeast cells entry into the stationary or quiescent states and the physiological consequences of harboring these prions throughout the lifespan of yeast cells. In the second part of my thesis, we addressed this issue using the [PSI+] prion as a model. Structurally different conformers of Sup35p aggregates can lead to distinct [PSI+] strains with different prion phenotypes. We found that Sup35p prion particles undergo growth phase-dependent ultrastructural and functional changes. Indeed, the size distributions of SDS-resistant core-prion particles significantly change during growth without affecting the structural information specific to each prion strain. The infectious properties of Sup35p prion particles undergo dramatic growth phase-dependent changes. Importantly, we found that while [PSI+] has little to no effects on the growth rates of yeasts, it robustly prolongs their chronological lifespan. Furthermore, this beneficial effect can then be permanently and efficiently fixed in the cells even when [PSI+] is subsequently lost. Similar genetic fixation of [PSI+]-induced epigenetic characteristics were previously observed and suggested [PSI+] (and possibly other prions) can act as transient evolutionary capacitators
Maluquer, de Motes i. Porta Carlos. "Estudi de l'excreció i estabilitat de prions en el medi." Doctoral thesis, Universitat de Barcelona, 2007. http://hdl.handle.net/10803/2405.
Full textEn els escorxadors on es processen animals de risc i animals infectats per malalties priòniques existeix un risc associat al material infecciós (teixit cerebral, medul·la, nerviós) que s'aboca a les aigües residuals. Mitjançant la detecció d'adenovirus porcins i bovins per PCR niada en aquestes aigües es va determinar la presència de contaminació d'origen animal específica de bestiar boví i porcí. En les primeres, gràcies al desenvolupament d'un protocol basat en centrifugacions i detecció per western-blot, es va determinar l'existència de nivells inferiors a 2-4 µg de material infecciós en 15 ml d'aigua residual. D'acord amb els estudis d'infectivitat presents en bibliografia, aquestes dades equivalen a una presència inferior a 10-6-10-7 dosis letals 50 per via oral en humans.
L'excreció de proteïnes priòniques per via fecal pot representar una entrada directa d'agents infecciosos en el medi. Un cop desenvolupat un mètode detecció basat en elució amb detergents i immunoprecipitació abans de la detecció per western-blot,es va determinar el patró d'excreció de prions en ratolins alimentats amb material infecciós i en ratolins en la fase terminal de la malaltia. En els darrers, els nivells es van mostrar indetectables, mentre que en els segons es van detectar prions 24-48 h post-administració. Aquestes dades indiquen la possibilitat d'una excreció de prions al medi en animals que ingereixen aliments contaminats.
Considerant l'elevada resistència dels prions als processos inactivadors, es va determinar la persistència de la molècula de PrPres en el medi i, concretament, en medis vehiculars com l'aigua. Mitjançant un protocol de concentració per ultracentrifugació i detecció per western-blot, es va estimar el temps necessari d'inactivació del 90% i 99% (t90 i t99) de la PrPres associada a l'agent infecciós EEB i scrapie inoculats en aigua de mar, aigua residual urbana i d'escorxadors. Les t99 obtingudes per a EEB foren de 25 a 60 dies, aproximadament del doble en el cas d'scrapie. i 10 cops superiors en el cas de solucions fisiològiques. La pèrdua de l'activitat infectiva està essent valorada actualment mitjançant bioassajos murins.
Les dades obtingudes en aquest estudi representen la primera valoració de la presència de proteïnes priòniques en el medi i de les seves possibles vies d'entrada, i suposen el desenvolupament de noves eines per al control del risc associat amb l'exposició als prions en el medi.
"Study of the excretion and stability of prions in the environment"
TEXT:
Prions are the causative agents of the transmissible spongiform encephalopathies: lethal diseases with long periods of incubation and associated to the deposition of a protease-resistant protein named PrPres. Concerns about the control and eradication of prion diseases increased with the identification of a new human disease (the variant of Creutzfeldt-Jakob disease) and its link with the bovine spongiform encephalopathy (BSE). This work evaluates for the first time the role of prion proteins as environmental contaminants, and the risk associated with its potential transmission.
Slaughterhouses processing risky and infected animals may drain wastewaters containing infective tissues (brain, spleen, nervous tissues). By the detection of porcine and bovine adenovirus by nested-PCR protocols in these waters, it was determined the presence of pollution from porcine and bovine origin. After the development of a centrifugation-based western-blot method, the former was shown to contain less than 2-4 µg of infectious tissue per 15 ml of wastewater. According to published infectivity studies, these levels are equivalent to lower concentrations than 10-6-10-7 oral lethal dose 50 for humans.
Prion excretion by the oral-fecal route may represent a direct input of infectious agents into the environment. A method based on elution with detergents, immunoprecipitation and western-blot detection was developed. Prion excretion was studied in terminally-sick infected mice and also on mice feed with infectious agents. The former show undetectable levels whereas the latter show prions 24-48 hours post-administration. Data presented could suggest a prion excretion in animals being feed with contaminated aliments.
Considering the high resistance of prions to inactivating procedures, it was analyzed the persistence of PrPres molecules in the environment, especially in vehicular media such as water. By a protocol based on ultracentrifugation and western-blot detection, the time needed for the 90 and 99% inactivation (t90 and t99) of PrPres associated to BSE and scrapie agents inoculated in seawater, urban and slaughterhouse sewage. t99 values obtained were from 25 to 60 days for BSE, 2-fold higher for scrapie and 10-fold higher for physiological solutions. The loss of infectivity is currently being analyzed by murine bioassays.
Data obtained in this study is the first evaluation of the presence of prion proteins in the environment and their potential routes of entrance, and represents the development of new tools for the control of the risk associated to the exposition to prions in the environment.
Gabriel, Pierre. "Équations de transport-fragmentation et applications aux maladies à prions." Phd thesis, Université Pierre et Marie Curie - Paris VI, 2011. http://tel.archives-ouvertes.fr/tel-00635281.
Full textJarnier, Dominique. "Les encéphalopathies familiales à prions : étude d'une famille avec insertion." Bordeaux 2, 1996. http://www.theses.fr/1996BOR23031.
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