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Your search keyword '"Requena, J. R."' showing total 5 results
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5 results on '"Requena, J. R."'

1. Bona fide atypical scrapie faithfully reproduced for the first time in a rodent model

Author

Ministerio de Economía y Competitividad (España), European Commission, Fundació La Marató de TV3, Generalitat de Catalunya, Vidal, Enric [0000-0002-4965-3286], Sánchez-Martín, Manuel A.[0000-0001-8370-1336], Eraña, Hasier [0000-0001-8776-4211], Lázaro, Sonia Pérez [0000-0002-2079-0711], Pérez-Castro, Miguel A.[0000-0003-2850-3470], Otero, Alicia [0000-0001-9075-2764], Charco, Jorge M. [0000-0003-3476-1855], Marín, Belén [0000-0002-1590-3347], López-Moreno, Rafael [0000-0002-2155-8965], Díaz-Domínguez, Carlos M. [0000-0002-0410-1963], Geijo, Mariví [0000-0002-3120-1038], Ordóñez, Montserrat [0000-0002-2389-7733], Cantero, Guillermo [0000-0003-4200-503X], di Bari, Michele [0000-0003-0943-6823], Lorenzo, Nuria L.[0000-0002-6444-6269], Pirisinu, Laura [0000-0002-6548-8225], Torres, Juan María [0000-0003-0443-9232], Béringue, V. [0000-0001-6706-5712], Telling, Glenn [0000-0002-6294-1805], Badiola, Juan J. [0000-0002-7173-7216], Pumarola, Martí [0000-0002-0935-7941], Bolea, Rosa [0000-0002-2746-3932], Nonno, Romolo [0000-0001-7556-1564], Requena, J. R. [0000-0003-1954-4975], Castilla, Joaquín [0000-0002-2216-1361], Vidal, Enric, Sánchez-Martín, Manuel Adolfo, Eraña, Hasier, Lázaro, Sonia Pérez, Pérez-Castro, Miguel A., Otero, Alicia, Charco, Jorge M., Marín, Belén, López-Moreno, Rafael, Díaz-Domínguez, Carlos M., Geijo, Mariví, Ordóñez, Montserrat, Cantero, Guillermo, di Bari, Michele, Lorenzo, Nuria L., Pirisinu, Laura, D'Agostino, Claudia, Torres, Juan María, Béringue, V., Telling, Glenn, Badiola, Juan J., Pumarola, Martí, Bolea, Rosa, Nonno, Romolo, Requena, Jesús R., Castilla, Joaquín, Ministerio de Economía y Competitividad (España), European Commission, Fundació La Marató de TV3, Generalitat de Catalunya, Vidal, Enric [0000-0002-4965-3286], Sánchez-Martín, Manuel A.[0000-0001-8370-1336], Eraña, Hasier [0000-0001-8776-4211], Lázaro, Sonia Pérez [0000-0002-2079-0711], Pérez-Castro, Miguel A.[0000-0003-2850-3470], Otero, Alicia [0000-0001-9075-2764], Charco, Jorge M. [0000-0003-3476-1855], Marín, Belén [0000-0002-1590-3347], López-Moreno, Rafael [0000-0002-2155-8965], Díaz-Domínguez, Carlos M. [0000-0002-0410-1963], Geijo, Mariví [0000-0002-3120-1038], Ordóñez, Montserrat [0000-0002-2389-7733], Cantero, Guillermo [0000-0003-4200-503X], di Bari, Michele [0000-0003-0943-6823], Lorenzo, Nuria L.[0000-0002-6444-6269], Pirisinu, Laura [0000-0002-6548-8225], Torres, Juan María [0000-0003-0443-9232], Béringue, V. [0000-0001-6706-5712], Telling, Glenn [0000-0002-6294-1805], Badiola, Juan J. [0000-0002-7173-7216], Pumarola, Martí [0000-0002-0935-7941], Bolea, Rosa [0000-0002-2746-3932], Nonno, Romolo [0000-0001-7556-1564], Requena, J. R. [0000-0003-1954-4975], Castilla, Joaquín [0000-0002-2216-1361], Vidal, Enric, Sánchez-Martín, Manuel Adolfo, Eraña, Hasier, Lázaro, Sonia Pérez, Pérez-Castro, Miguel A., Otero, Alicia, Charco, Jorge M., Marín, Belén, López-Moreno, Rafael, Díaz-Domínguez, Carlos M., Geijo, Mariví, Ordóñez, Montserrat, Cantero, Guillermo, di Bari, Michele, Lorenzo, Nuria L., Pirisinu, Laura, D'Agostino, Claudia, Torres, Juan María, Béringue, V., Telling, Glenn, Badiola, Juan J., Pumarola, Martí, Bolea, Rosa, Nonno, Romolo, Requena, Jesús R., and Castilla, Joaquín

Abstract

Atypical Scrapie, which is not linked to epidemics, is assumed to be an idiopathic spontaneous prion disease in small ruminants. Therefore, its occurrence is unlikely to be controlled through selective breeding or other strategies as it is done for classical scrapie outbreaks. Its spontaneous nature and its sporadic incidence worldwide is reminiscent of the incidence of idiopathic spontaneous prion diseases in humans, which account for more than 85% of the cases in humans. Hence, developing animal models that consistently reproduce this phenomenon of spontaneous PrP misfolding, is of importance to study the pathobiology of idiopathic spontaneous prion disorders. Transgenic mice overexpressing sheep PrPC with I112 polymorphism (TgShI112, 1-2 × PrP levels compared to sheep brain) manifest clinical signs of a spongiform encephalopathy spontaneously as early as 380 days of age. The brains of these animals show the neuropathological hallmarks of prion disease and biochemical analyses of the misfolded prion protein show a ladder-like PrPres pattern with a predominant 7-10 kDa band. Brain homogenates from spontaneously diseased transgenic mice were inoculated in several models to assess their transmissibility and characterize the prion strain generated: TgShI112 (ovine I112 ARQ PrPC), Tg338 (ovine VRQ PrPC), Tg501 (ovine ARQ PrPC), Tg340 (human M129 PrPC), Tg361 (human V129 PrPC), TgVole (bank vole I109 PrPC), bank vole (I109I PrPC), and sheep (AHQ/ARR and AHQ/AHQ churra-tensina breeds). Our analysis of the results of these bioassays concludes that the strain generated in this model is indistinguishable to that causing atypical scrapie (Nor98). Thus, we present the first faithful model for a bona fide, transmissible, ovine, atypical scrapie prion disease.

Published
2022

2. Full atomistic model of prion structure and conversion

Author

Spagnolli, G, Rigoli, M, Orioli, S, Sevillano, A, Faccioli, P, Wille, H, Biasini, E, Requena, J, Spagnolli G., Rigoli M., Orioli S., Sevillano A. M., Faccioli P., Wille H., Biasini E., Requena J. R., Spagnolli, G, Rigoli, M, Orioli, S, Sevillano, A, Faccioli, P, Wille, H, Biasini, E, Requena, J, Spagnolli G., Rigoli M., Orioli S., Sevillano A. M., Faccioli P., Wille H., Biasini E., and Requena J. R.

Published
2019

3. Ok google, how could i design therapeutics against prion diseases?

Author

Rigoli, M, Spagnolli, G, Faccioli, P, Requena, J, Biasini, E, Rigoli M., Spagnolli G., Faccioli P., Requena J. R., Biasini E., Rigoli, M, Spagnolli, G, Faccioli, P, Requena, J, Biasini, E, Rigoli M., Spagnolli G., Faccioli P., Requena J. R., and Biasini E.

Abstract

A number of previous successful attempts in the search for therapeutics for a variety of human pathologies highlight the importance of computational technologies in the drug discovery pipeline. This approach, often referred to as computer-aided drug design, is unfortunately inapplicable when the precise information regarding the three-dimensional structure of disease-associated proteins or the mechanism by which they are altered to generate misfolded isoforms are missing. A typical example is represented by prion diseases, fatal pathologies of the nervous system characterized by the conformational conversion of a physiological protein called PrP C into a misfolded and infectious isoform referred to as PrP Sc . Missing information regarding the atomic structure of PrP Sc as well as the mechanism of templated conversion of PrP C has severely halted the discovery of effective therapies for prion diseases. In this manuscript, we review emerging opportunities to apply computer-aided techniques to target PrP C , PrP Sc or to design inhibitors of prion replication, and discuss how these fast-evolving technologies could lay the groundwork for the application of entirely novel rational drug design schemes for these devastating pathologies.

Published
2019

4. The Priority position paper: protecting Europe's food chain from prions

Author

Tiziana Sonati, Krister Kristensson, Mario Nuvolone, Ludwig E. Hoelzle, Jesús R. Requena, Neil A. Mabbott, Giuseppe Legname, Albert Taraboulos, Juan María Torres, José Antonio del Río, Chiara Zurzolo, Carsten Korth, Alex Raeber, Olivier Andreoletti, Paul Laeven, Byron Calgua, Juan Carlos Espinosa, Andreas Müller-Schiffmann, Matthias Schmitz, Zheng-Xin Yan, Peter J. Peters, Rosina Girones, Inga Zerr, Adriano Aguzzi, Franziska Kuhn, Reinhard Böhm, S. Godsave, Eva Mitrova, Michael R. Knittler, Lothar Stitz, Klaus Roth, Karen L. Brown, Sylvie L. Benestad, Marion Simmons, Björn Schroeder, Patricia Aguilar-Calvo, CIMUS Biomedical Research Institute [Santiago de Compostela], Karolinska Institutet [Stockholm], Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Trafic membranaire et Pathogénèse, Institut Pasteur [Paris], Animal and Plant Health Agency [Weybridge] (APHA), Centro de Investigacion en Sanidad Animal (INIA-CISA), Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria = National Institute for Agricultural and Food Research and Technology (INIA), Universität Zürich [Zürich] = University of Zurich (UZH), Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Norwegian Veterinary Institute [Oslo], University of Hohenheim, University of Edinburgh, University of Barcelona, Institute for Bioengineering of Catalonia [Barcelona] (IBEC), Netherlands Cancer Institute (NKI), Antoni van Leeuwenhoek Hospital, Friedrich-Loeffler-Institut (FLI), Prionics [Zurich], Laboratory of Prion Biology, Scuola Internazionale Superiore di Studi Avanzati / International School for Advanced Studies (SISSA / ISAS), Maastricht University [Maastricht], Slovak Medical University of Bratislava (SMU), The Maastricht Multimodal Molecular Imaging Institute, SMP GmbH [Tübingen], Universitätmedizin Göttingen, The Hebrew University of Jerusalem (HUJ), DZNE Göttingen, Funding was provided by the EC through FP7 222887 'Priority.', European Project: 222887,EC:FP7:KBBE,FP7-KBBE-2007-2A,PRIORITY(2009), Requena, J. R., Kristensson, K., Korth, C., Zurzolo, C., Simmons, M., Aguilar-Calvo, P., Aguzzi, A., Andreoletti, O., Benestad, S. L., Bohm, R., Brown, K., Calgua, B., del Rio, J. A., Espinosa, J. C., Girones, R., Godsave, S., Hoelzle, L. E., Knittler, M. R., Kuhn, F., Legname, G., Laeven, P., Mabbott, N., Mitrova, E., Muller-Schiffmann, A., Nuvolone, M., Peters, P. J., Raeber, A., Roth, K., Schmitz, M., Schroeder, B., Sonati, T., Stitz, L., Taraboulos, A., Torres, J. M., Yan, Z. -X., Zerr, I., RS: M4I - Nanoscopy, Institute of Nanoscopy (IoN), Universidade de Santiago de Compostela [Spain] (USC ), Institut Pasteur [Paris] (IP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT), Heinrich-Heine-Universität Düsseldorf [Düsseldorf], CISA, Instituto Nacional de Investigaciones Agronomicas, University of Zürich [Zürich] (UZH), Norwegian Veterinary Institute, and Medical University of Slovakia [Bratislava]

Subjects
0301 basic medicine, Scrapie, prevention & control [Encephalopathy, Bovine Spongiform], Settore BIO/09 - Fisiologia, Biochemistry, Prion Diseases, prevention & control [Prion Diseases], BSE, Early Diagnosi, Applied research, media_common, 2. Zero hunger, epidemiology [Scrapie], epidemiology [Europe], atypical BSE, atypical scrapie, CJD, prion, scrapie, diagnosis [Scrapie], 3. Good health, Encephalopathy, Bovine Spongiform, Europe, Infectious Diseases, Perspective, Small and medium-sized enterprises, Risk assessment, Human, diagnosis [Encephalopathy, Bovine Spongiform], epidemiology [Prion Diseases], medicine.medical_specialty, Food Chain, Prions, Bovine spongiform encephalopathy, transmission [Scrapie], [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, 03 medical and health sciences, Cellular and Molecular Neuroscience, adverse effects [Animal Feed], analysis [Prions], isolation & purification [Prions], ddc:570, transmission [Encephalopathy, Bovine Spongiform], Development economics, medicine, media_common.cataloged_instance, Animals, Humans, European union, pathogenicity [Prions], Animal, Public health, Cell Biology, medicine.disease, prevention & control [Scrapie], Virology, Animal Feed, diagnosis [Prion Diseases], Prion Disease, 030104 developmental biology, Early Diagnosis, transmission [Prion Diseases], metabolism [Prions], Position paper, Cattle, epidemiology [Encephalopathy, Bovine Spongiform]
Abstract

Bovine spongiform encephalopathy (BSE) created a global European crisis in the 1980s and 90s, with very serious health and economic implications. Classical BSE now appears to be under control, to a great extent as a result of a global research effort that identified the sources of prions in meat and bone meal (MBM) and developed new animal-testing tools that guided policy. Priority (www.prionpriority.eu) was a European Union (EU) Framework Program 7 (FP7)-funded project through which 21 European research institutions and small and medium enterprises (SMEs) joined efforts between 2009 and 2014, to conduct coordinated basic and applied research on prions and prion diseases. At the end of the project, the Priority consortium drafted a position paper (www.prionpriority.eu/Priority position paper) with its main conclusions. In the present opinion paper, we summarize these conclusions. With respect to the issue of re-introducing ruminant protein into the feed-chain, our opinion is that sustaining an absolute ban on feeding ruminant protein to ruminants is essential. In particular, the spread and impact of non-classical forms of scrapie and BSE in ruminants is not fully understood and the risks cannot be estimated. Atypical prion agents will probably continue to represent the dominant form of prion diseases in the near future in Europe. Atypical L-type BSE has clear zoonotic potential, as demonstrated in experimental models. Similarly, there are now data indicating that the atypical scrapie agent can cross various species barriers. More epidemiological data from large cohorts are necessary to reach any conclusion on the impact of its transmissibility on public health. Re-evaluations of safety precautions may become necessary depending on the outcome of these studies. Intensified searching for molecular determinants of the species barrier is recommended, since this barrier is key for important policy areas and risk assessment. Understanding the structural basis for strains and the basis for adaptation of a strain to a new host will require continued fundamental research, also needed to understand mechanisms of prion transmission, replication and how they cause nervous system dysfunction and death. Early detection of prion infection, ideally at a preclinical stage, also remains crucial for development of effective treatment strategies. © 2016 The Author(s). Published with license by Taylor & Francis Group, LLC.

Published
2016
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5. The Structure of Mammalian Prions and Their Aggregates.

Author

Vázquez-Fernández E, Young HS, Requena JR, and Wille H

Subjects
Amyloid chemistry, Animals, Crystallization, Humans, Models, Molecular, Prions metabolism, Prions ultrastructure, Mammals metabolism, Prions chemistry, Protein Aggregates
Abstract

Prion diseases, such as Creutzfeldt-Jakob disease in humans, bovine spongiform encephalopathy in cattle, chronic wasting disease in cervids (i.e., deer, elk, moose, and reindeer), and sheep scrapie, are caused by the misfolding of the cellular prion protein (PrP C ) into a disease-causing conformer (PrP Sc ). PrP C is a normal, GPI-anchored protein that is expressed on the surface of neurons and other cell types. The structure of PrP C is well understood, based on studies of recombinant PrP, which closely mimics the structure of native PrP C . In contrast, PrP Sc is prone to aggregate into a variety of quaternary structures, such as oligomers, amorphous aggregates, and amyloid fibrils. The propensity of PrP Sc to assemble into these diverse forms of aggregates is also responsible for our limited knowledge about its structure. Then again, the repeating nature of certain regular PrP Sc aggregates has allowed (lower resolution) insights into the structure of the infectious conformer, establishing a four-rung β-solenoid structure as a key element of its architecture., (© 2017 Elsevier Inc. All rights reserved.)

Published
2017
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