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15 results on '"Espinosa Martín, Juan Carlos [0000-0002-6719-9902]"'

1. Transgenic Mouse Models for the Study of Neurodegenerative Diseases

Author

Marín-Moreno, Alba [0000-0002-4023-6398], Canoyra, Sara [0000-0001-6371-8122], Fernández-Borges, N. [0000-0001-8298-5189], Espinosa Martín, Juan Carlos [0000-0002-6719-9902], Torres, Juan María [0000-0003-0443-9232], Marín-Moreno, Alba, Canoyra, Sara, Fernández-Borges, N., Espinosa Martín, Juan Carlos, Torres, Juan María, Marín-Moreno, Alba [0000-0002-4023-6398], Canoyra, Sara [0000-0001-6371-8122], Fernández-Borges, N. [0000-0001-8298-5189], Espinosa Martín, Juan Carlos [0000-0002-6719-9902], Torres, Juan María [0000-0003-0443-9232], Marín-Moreno, Alba, Canoyra, Sara, Fernández-Borges, N., Espinosa Martín, Juan Carlos, and Torres, Juan María

Abstract

Neurodegenerative diseases (NDs) are some of the most important health challenges modern medicine and advanced societies face. Indeed, the number of patients affected by one of these illnesses will increase in the following years at the same rate that human life expectancy allows us to live longer. Despite many years of research, NDs remain invariably fatal. A complete understanding of the exact mechanisms leading to neuronal death, which will ideally allow preclinical detection and the development of effective treatments, has not yet been achieved. However, a great deal of information about ND pathology and the search for possible therapies has been acquired using animal models and more precisely transgenic mouse models. In this review, the main contributions of these powerful research tools in NDs as well as their advantages and caveats are discussed.

Published
2023

2. Validation of Plasma and CSF Neurofilament Light Chain as an Early Marker for Sporadic Creutzfeldt-Jakob Disease

Author

Fundació La Marató de TV3, Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España), Alzheimer Forschung Initiative, Federal Ministry of Health (Germany), European Commission, Schmitz, Matthias [0000-0002-5502-681X], Canaslan, Sezgi [0000-0001-5366-129X], Espinosa Martín, Juan Carlos [0000-0002-6719-9902], Fernández-Borges, N. [0000-0001-8298-5189], Villar-Piqué, Anna [0000-0002-5528-208X], Torres, Juan María [0000-0003-0443-9232], Zerr, I. [0000-0002-6722-2463], Schmitz, Matthias, Canaslan, Sezgi, Espinosa Martín, Juan Carlos, Fernández-Borges, N., Villar-Piqué, Anna, Llorens, Franc, Varges, Daniela, Maass, Fabian, Torres, Juan María, Hermann, Peter, Zerr, I., Fundació La Marató de TV3, Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España), Alzheimer Forschung Initiative, Federal Ministry of Health (Germany), European Commission, Schmitz, Matthias [0000-0002-5502-681X], Canaslan, Sezgi [0000-0001-5366-129X], Espinosa Martín, Juan Carlos [0000-0002-6719-9902], Fernández-Borges, N. [0000-0001-8298-5189], Villar-Piqué, Anna [0000-0002-5528-208X], Torres, Juan María [0000-0003-0443-9232], Zerr, I. [0000-0002-6722-2463], Schmitz, Matthias, Canaslan, Sezgi, Espinosa Martín, Juan Carlos, Fernández-Borges, N., Villar-Piqué, Anna, Llorens, Franc, Varges, Daniela, Maass, Fabian, Torres, Juan María, Hermann, Peter, and Zerr, I.

Abstract

Biomarkers are becoming increasingly important for the differential diagnosis of neurodegenerative diseases. Previous observations indicated neurofilament light chain (NfL) as a potential blood-based biomarker for sporadic Creutzfeldt-Jakob disease (sCJD). Here, we investigated the stability, inter-assay/intra-assay variation and the regulation of NfL levels in CSF and plasma in a large cohort of sCJD patients by using a single-molecule array (SIMOA). We defined cutoffs for an accurate diagnosis and measured plasma NfL level in prion-infected mice models at different time points to identify the potential dynamics throughout the disease. Our analyses confirmed CSF and plasma NfL as stable and consistent marker for sCJD. Receiver operating characteristic (ROC) curve analysis showed an AUC of 0.92-0.93 to distinguish sCJD from control groups. Newly defined cutoffs revealed good diagnostic accuracies of CSF and plasma NfL, indicated by a sensitivity of 80-83.5% and a specificity of 87.4-91%. Studies on two humanized prion-infected mice lines (Tg340-PRNP 129MM and Tg361-PRNP 129VV) revealed increased plasma NfL levels in a late pre-clinical or very early clinical stage between 120-150 days post-inoculation. In conclusion, our work supports the potential use of CSF and plasma NfL as a very early biomarker in sCJD diagnostic with good diagnostic accuracies.

Published
2022

3. TREM2 expression in the brain and biological fluids in prion diseases

Author

Generalitat de Catalunya, Instituto de Salud Carlos III, Fundació La Marató de TV3, European Commission, Swedish Research Council, Ministero della Salute, Alzheimer Society of Canada, Ministerio de Ciencia, Innovación y Universidades (España), Diaz-Lucena, Daniela [0000-0002-0262-1498], Kruse, Niels [0000-0002-4036-8999], Thüne, Katrin [0000-0001-9906-4212], Villar-Piqué, Anna [0000-0002-5528-208X], da Cunha, Jose Eriton Gomes [0000-0002-0603-7782], López-Pérez, Óscar [0000-0003-2454-2114], Andrés-Benito, Pol [0000-0003-3000-0338], Ladogana, Anna [0000-0002-7504-6906], Calero, Miguel [0000-0001-5366-3324], Vidal, Enric [0000-0002-4965-3286], Pineau, Hailey [0000-0002-8703-5825], Sim, Valerie [0000-0002-0088-8666], Zetterberg, Henrik [0000-0003-3930-4354], Blennow, Kaj [0000-0002-1890-4193], Río, José Antonio del [0000-0002-5214-4909], Marín-Moreno, Alba [0000-0002-4023-6398], Espinosa Martín, Juan Carlos [0000-0002-6719-9902], Torres, Juan María [0000-0003-0443-9232], Sánchez-Valle, Raquel [0000-0001-7750-896X], Mollenhauer, Brit [0000-0001-8437-3645], Ferrer, Isidre [0000-0001-9888-8754], Zerr, I. [0000-0002-6722-2463], Diaz-Lucena, Daniela, Kruse, Niels, Thüne, Katrin, Schmitz, Matthias, Villar-Piqué, Anna, da Cunha, Jose Eriton Gomes, Hermann, Peter, López-Pérez, Óscar, Andrés-Benito, Pol, Ladogana, Anna, Calero, Miguel, Vidal, Enric, Riggert, Joachim, Pineau, Hailey, Sim, Valerie, Zetterberg, Henrik, Blennow, Kaj, Del Río, J. A., Marín-Moreno, Alba, Espinosa Martín, Juan Carlos, Torres, Juan María, Sánchez-Valle, Raquel, Mollenhauer, Brit, Ferrer, Isidre, Zerr, I., Llorens, Franc, Generalitat de Catalunya, Instituto de Salud Carlos III, Fundació La Marató de TV3, European Commission, Swedish Research Council, Ministero della Salute, Alzheimer Society of Canada, Ministerio de Ciencia, Innovación y Universidades (España), Diaz-Lucena, Daniela [0000-0002-0262-1498], Kruse, Niels [0000-0002-4036-8999], Thüne, Katrin [0000-0001-9906-4212], Villar-Piqué, Anna [0000-0002-5528-208X], da Cunha, Jose Eriton Gomes [0000-0002-0603-7782], López-Pérez, Óscar [0000-0003-2454-2114], Andrés-Benito, Pol [0000-0003-3000-0338], Ladogana, Anna [0000-0002-7504-6906], Calero, Miguel [0000-0001-5366-3324], Vidal, Enric [0000-0002-4965-3286], Pineau, Hailey [0000-0002-8703-5825], Sim, Valerie [0000-0002-0088-8666], Zetterberg, Henrik [0000-0003-3930-4354], Blennow, Kaj [0000-0002-1890-4193], Río, José Antonio del [0000-0002-5214-4909], Marín-Moreno, Alba [0000-0002-4023-6398], Espinosa Martín, Juan Carlos [0000-0002-6719-9902], Torres, Juan María [0000-0003-0443-9232], Sánchez-Valle, Raquel [0000-0001-7750-896X], Mollenhauer, Brit [0000-0001-8437-3645], Ferrer, Isidre [0000-0001-9888-8754], Zerr, I. [0000-0002-6722-2463], Diaz-Lucena, Daniela, Kruse, Niels, Thüne, Katrin, Schmitz, Matthias, Villar-Piqué, Anna, da Cunha, Jose Eriton Gomes, Hermann, Peter, López-Pérez, Óscar, Andrés-Benito, Pol, Ladogana, Anna, Calero, Miguel, Vidal, Enric, Riggert, Joachim, Pineau, Hailey, Sim, Valerie, Zetterberg, Henrik, Blennow, Kaj, Del Río, J. A., Marín-Moreno, Alba, Espinosa Martín, Juan Carlos, Torres, Juan María, Sánchez-Valle, Raquel, Mollenhauer, Brit, Ferrer, Isidre, Zerr, I., and Llorens, Franc

Abstract

Triggering receptor expressed on myeloid cells 2 (TREM2) is an innate immune cell surface receptor that regulates microglial function and is involved in the pathophysiology of several neurodegenerative diseases. Its soluble form (sTREM2) results from shedding of the TREM2 ectodomain. The role of TREM2 in prion diseases, a group of rapidly progressive dementias remains to be elucidated. In the present study, we analysed the expression of TREM2 and its main sheddase ADAM10 in the brain of sporadic Creutzfeldt-Jakob disease (sCJD) patients and evaluated the role of CSF and plasma sTREM2 as a potential diagnostic marker of prion disease. Our data indicate that, compared to controls, TREM2 is increased in sCJD patient brains at the mRNA and protein levels in a regional and subtype dependent fashion, and expressed in a subpopulation of microglia. In contrast, ADAM10 is increased at the protein, but not the mRNA level, with a restricted neuronal expression. Elevated CSF sTREM2 is found in sCJD, genetic CJD with mutations E200K and V210I in the prion protein gene (PRNP), and iatrogenic CJD, as compared to healthy controls (HC) (AUC = 0.78-0.90) and neurological controls (AUC = 0.73-0.85), while CSF sTREM2 is unchanged in fatal familial insomnia. sTREM2 in the CSF of cases with Alzheimer's disease, and multiple sclerosis was not significantly altered in our series. CSF sTREM2 concentrations in sCJD are PRNP codon 129 and subtype-related, correlate with CSF 14-3-3 positivity, total-tau and YKL-40, and increase with disease progression. In plasma, sTREM2 is increased in sCJD compared with HC (AUC = 0.80), displaying positive correlations with plasma total-tau, neurofilament light, and YKL-40. We conclude that comparative study of TREM2 in brain and biological fluids of prion diseases reveals TREM2 to be altered in human prion diseases with a potential value in target engagement, patient stratification, and disease monitoring.

Published
2021

4. Porcine Prion Protein as a Paradigm of Limited Susceptibility to Prion Strain Propagation

Author

Ministerio de Economía y Competitividad (España), Agencia Estatal de Investigación (España), European Commission, Food Standards Agency (UK), Espinosa Martín, Juan Carlos [0000-0002-6719-9902], Marín-Moreno, Alba (0000-0002-4023-6398), Benestad, Sylvie L (0000-0002-3011-0484), Andreoletti, Olivier (0000-0002-7369-6016), Torres, Juan María (0000-0003-0443-9232), Espinosa Martín, Juan Carlos, Marín-Moreno, Alba, Aguilar-Calvo, Patricia, Benestad, Sylvie L., Andréoletti, Olivier, Torres, Juan María, Ministerio de Economía y Competitividad (España), Agencia Estatal de Investigación (España), European Commission, Food Standards Agency (UK), Espinosa Martín, Juan Carlos [0000-0002-6719-9902], Marín-Moreno, Alba (0000-0002-4023-6398), Benestad, Sylvie L (0000-0002-3011-0484), Andreoletti, Olivier (0000-0002-7369-6016), Torres, Juan María (0000-0003-0443-9232), Espinosa Martín, Juan Carlos, Marín-Moreno, Alba, Aguilar-Calvo, Patricia, Benestad, Sylvie L., Andréoletti, Olivier, and Torres, Juan María

Abstract

Although experimental transmission of bovine spongiform encephalopathy (BSE) to pigs and transgenic mice expressing pig cellular prion protein (PrPC) (porcine PrP [PoPrP]-Tg001) has been described, no natural cases of prion diseases in pig were reported. This study analyzed pig-PrPC susceptibility to different prion strains using PoPrP-Tg001 mice either as animal bioassay or as substrate for protein misfolding cyclic amplification (PMCA). A panel of isolates representatives of different prion strains was selected, including classic and atypical/Nor98 scrapie, atypical-BSE, rodent scrapie, human Creutzfeldt-Jakob-disease and classic BSE from different species. Bioassay proved that PoPrP-Tg001-mice were susceptible only to the classic BSE agent, and PMCA results indicate that only classic BSE can convert pig-PrPC into scrapie-type PrP (PrPSc), independently of the species origin. Therefore, conformational flexibility constraints associated with pig-PrP would limit the number of permissible PrPSc conformations compatible with pig-PrPC, thus suggesting that pig-PrPC may constitute a paradigm of low conformational flexibility that could confer high resistance to the diversity of prion strains.

Published
2021

5. Classical scrapie in small ruminants is caused by at least four different prion strains

Author

European Commission, Ministerio de Economía y Competitividad (España), CSIC - Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Marín-Moreno, Alba [0000-0002-4023-6398], Aguilar-Calvo, Patricia [0000-0001-5859-0240], Espinosa Martín, Juan Carlos [0000-0002-6719-9902], Zamora-Ceballos, María [0000-0002-4694-2365], Pitarch, José Luis [0000-0003-3016-9125], Fernández-Borges, N. [0000-0001-8298-5189], Orge, Leonor [0000-0002-2673-2758], Andréoletti, Olivier [0000-0002-7369-6016], Nonno, Romolo [0000-0001-7556-1564], Torres, Juan María [0000-0003-0443-9232], Marín-Moreno, Alba, Aguilar-Calvo, Patricia, Espinosa Martín, Juan Carlos, Zamora-Ceballos, María, Pitarch, José Luis, Fernández-Borges, N., Orge, Leonor, Andréoletti, Olivier, Nonno, Romolo, Torres, Juan María, European Commission, Ministerio de Economía y Competitividad (España), CSIC - Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Marín-Moreno, Alba [0000-0002-4023-6398], Aguilar-Calvo, Patricia [0000-0001-5859-0240], Espinosa Martín, Juan Carlos [0000-0002-6719-9902], Zamora-Ceballos, María [0000-0002-4694-2365], Pitarch, José Luis [0000-0003-3016-9125], Fernández-Borges, N. [0000-0001-8298-5189], Orge, Leonor [0000-0002-2673-2758], Andréoletti, Olivier [0000-0002-7369-6016], Nonno, Romolo [0000-0001-7556-1564], Torres, Juan María [0000-0003-0443-9232], Marín-Moreno, Alba, Aguilar-Calvo, Patricia, Espinosa Martín, Juan Carlos, Zamora-Ceballos, María, Pitarch, José Luis, Fernández-Borges, N., Orge, Leonor, Andréoletti, Olivier, Nonno, Romolo, and Torres, Juan María

Abstract

The diversity of goat scrapie strains in Europe has recently been studied using bioassays in a wide collection of rodent models, resulting in the classification of classical scrapie into four different categories. However, the sole use of the first passage does not lead to isolate adaptation and identification of the strains involved and might therefore lead to misclassification of some scrapie isolates. Therefore, this work reports the complete transmission study of a wide collection of goat transmissible spongiform encephalopathy (TSE) isolates by intracranial inoculation in two transgenic mouse lines overexpressing either small ruminant (TgGoat-ARQ) or bovine (TgBov) PrPC. To compare scrapie strains in sheep and goats, sheep scrapie isolates from different European countries were also included in the study. Once the species barrier phenomenon was overcome, an accurate classification of the isolates was attained. Thus, the use of just two rodent models allowed us to fully differentiate at least four different classical scrapie strains in small ruminants and to identify isolates containing mixtures of strains. This work reinforces the idea that classical scrapie in small ruminants is a prion disease caused by multiple different prion strains and not by a single strain, as is the case for epidemic classical bovine spongiform encephalopathy (BSE-C). In addition, the clear dissimilarity between the different scrapie strains and BSE-C does not support the idea that classical scrapie is the origin of epidemic BSE-C.

Published
2021

6. Canine D163-PrP polymorphic variant does not provide complete protection against prion infection in small ruminant PrP context

Author

Ministerio de Ciencia e Innovación (España), Ministerio de Economía y Competitividad (España), European Commission, CSIC - Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Marín-Moreno, Alba [0000-0002-4023-6398], Espinosa Martín, Juan Carlos [0000-0002-6719-9902], Fernández-Borges, N. [0000-0001-8298-5189], González, Lorenzo [0000-0003-1513-1399], Torres, Juan María [0000-0003-0443-9232], Marín-Moreno, Alba, Espinosa Martín, Juan Carlos, Aguilar-Calvo, Patricia, Fernández-Borges, N., Pitarch, José Luis, González, Lorenzo, Torres, Juan María, Ministerio de Ciencia e Innovación (España), Ministerio de Economía y Competitividad (España), European Commission, CSIC - Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Marín-Moreno, Alba [0000-0002-4023-6398], Espinosa Martín, Juan Carlos [0000-0002-6719-9902], Fernández-Borges, N. [0000-0001-8298-5189], González, Lorenzo [0000-0003-1513-1399], Torres, Juan María [0000-0003-0443-9232], Marín-Moreno, Alba, Espinosa Martín, Juan Carlos, Aguilar-Calvo, Patricia, Fernández-Borges, N., Pitarch, José Luis, González, Lorenzo, and Torres, Juan María

Abstract

E/D163 polymorphism of dog prion protein (PrP) has been recently proposed as the variant responsible for canid prion resistance. To further investigate the protective role of this variant against prion replication, the transgenic mouse model OvPrP-Tg532 expressing sheep/goat PrP carrying the substitution D162 (equivalent to D163 position of dog PrP) was generated and intracranially inoculated with a broad collection of small ruminant prion strains. OvPrP-Tg532 mice showed resistance to classical bovine spongiform encephalopathy (BSE) from sheep and some classical scrapie isolates from sheep and goat but were susceptible to ovine atypical L-BSE and numerous classical scrapie isolates. Strikingly, some of these classical scrapie isolates showed a shift in their prion strain properties. These results suggest that other PrP residues apart from E/D163 variant of dog PrP or factors distinct than PrP may participate in prion resistance of canids and that different factors may be required for D162 sheep PrP to provide effective protection to sheep against ruminant prions.

Published
2021

7. Homozygous R136S mutation in PRNP gene causes inherited early onset prion disease

Author

Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), Fundació La Marató de TV3, CSIC - Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Ximelis, Teresa [0000-0002-9634-1496], Marín-Moreno, Alba [0000-0002-4023-6398], Espinosa Martín, Juan Carlos [0000-0002-6719-9902], Eraña, Hasier [0000-0001-8776-4211], Charco, Jorge M. [0000-0003-3476-1855], Alcolea, Daniel [0000-0002-3819-3245], González-Roca, Eva [0000-0002-1126-0321], Aldecoa, Iban [0000-0001-5774-7453], Molina-Porcel, Laura [0000-0003-4068-8578], Parchi, Piero [0000-0002-9444-9524], Rossi, Marcello [0000-0002-8125-6571], Castilla, Joaquín [0000-0002-2216-1361], Ruiz-García, Raquel [0000-0002-8403-3613], Gelpi, Ellen [0000-0003-2948-4187], Torres, Juan María [0000-0003-0443-9232], Sánchez-Valle, Raquel [0000-0001-7750-896X], Ximelis, Teresa, Marín-Moreno, Alba, Espinosa Martín, Juan Carlos, Eraña, Hasier, Charco, Jorge M., Hernández, Isabel, Riveira, Carmen, Alcolea, Daniel, González-Roca, Eva, Aldecoa, Iban, Molina-Porcel, Laura, Parchi, Piero, Rossi, Marcello, Castilla, Joaquín, Ruiz-García, Raquel, Gelpi, Ellen, Torres, Juan María, Sánchez-Valle, Raquel, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), Fundació La Marató de TV3, CSIC - Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Ximelis, Teresa [0000-0002-9634-1496], Marín-Moreno, Alba [0000-0002-4023-6398], Espinosa Martín, Juan Carlos [0000-0002-6719-9902], Eraña, Hasier [0000-0001-8776-4211], Charco, Jorge M. [0000-0003-3476-1855], Alcolea, Daniel [0000-0002-3819-3245], González-Roca, Eva [0000-0002-1126-0321], Aldecoa, Iban [0000-0001-5774-7453], Molina-Porcel, Laura [0000-0003-4068-8578], Parchi, Piero [0000-0002-9444-9524], Rossi, Marcello [0000-0002-8125-6571], Castilla, Joaquín [0000-0002-2216-1361], Ruiz-García, Raquel [0000-0002-8403-3613], Gelpi, Ellen [0000-0003-2948-4187], Torres, Juan María [0000-0003-0443-9232], Sánchez-Valle, Raquel [0000-0001-7750-896X], Ximelis, Teresa, Marín-Moreno, Alba, Espinosa Martín, Juan Carlos, Eraña, Hasier, Charco, Jorge M., Hernández, Isabel, Riveira, Carmen, Alcolea, Daniel, González-Roca, Eva, Aldecoa, Iban, Molina-Porcel, Laura, Parchi, Piero, Rossi, Marcello, Castilla, Joaquín, Ruiz-García, Raquel, Gelpi, Ellen, Torres, Juan María, and Sánchez-Valle, Raquel

Abstract

More than 40 pathogenic heterozygous PRNP mutations causing inherited prion diseases have been identified to date. Recessive inherited prion disease has not been described to date.

Published
2021

8. Two distinct conformers of PrPD type 1 of sporadic Creutzfeldt-Jakob disease with codon 129VV genotype faithfully propagate in vivo

Author

Ministerio de Economía, Industria y Competitividad (España), Fundació La Marató de TV3, CSIC - Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Cali, Ignazio [0000-0001-5770-3848], Espinosa Martín, Juan Carlos [0000-0002-6719-9902], Marín-Moreno, Alba [0000-0002-4023-6398], Aslam, Rabail [0000-0002-0717-6821], Kitamoto, Tetsuyuki [000-0002-6298-2439], Torres, Juan María [0000-0003-0443-9232], Gambetti, Pierluigi [0000-0002-9843-5162], Cali, Ignazio, Espinosa Martín, Juan Carlos, Nemani, Satish K., Marín-Moreno, Alba, Camacho, Manuel V., Aslam, Rabail, Kitamoto, Tetsuyuki, Appleby, Brian S., Torres, Juan María, Gambetti, Pierluigi, Ministerio de Economía, Industria y Competitividad (España), Fundació La Marató de TV3, CSIC - Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Cali, Ignazio [0000-0001-5770-3848], Espinosa Martín, Juan Carlos [0000-0002-6719-9902], Marín-Moreno, Alba [0000-0002-4023-6398], Aslam, Rabail [0000-0002-0717-6821], Kitamoto, Tetsuyuki [000-0002-6298-2439], Torres, Juan María [0000-0003-0443-9232], Gambetti, Pierluigi [0000-0002-9843-5162], Cali, Ignazio, Espinosa Martín, Juan Carlos, Nemani, Satish K., Marín-Moreno, Alba, Camacho, Manuel V., Aslam, Rabail, Kitamoto, Tetsuyuki, Appleby, Brian S., Torres, Juan María, and Gambetti, Pierluigi

Abstract

Current classifications of sporadic Creutzfeldt-Jakob disease (sCJD) identify five subtypes associated with different disease phenotypes. Most of these histopathological phenotypes (histotypes) co-distribute with distinct pairings of methionine (M)/valine (V) genotypes at codon 129 of the prion protein (PrP) gene and the type (1 or 2) of the disease-associated PrP (PrPD). Types 1 and 2 are defined by the molecular mass (~ 21 kDa and ~ 19 kDa, respectively) of the unglycosylated isoform of the proteinase K-resistant PrPD (resPrPD). We recently reported that the sCJDVV1 subtype (129VV homozygosity paired with PrPD type 1, T1) shows an electrophoretic profile where the resPrPD unglycosylated isoform is characterized by either one of two single bands of ~ 20 kDa (T120) and ~ 21 kDa (T121), or a doublet of ~ 21-20 kDa (T121-20). We also showed that T120 and T121 in sCJDVV have different conformational features but are associated with indistinguishable histotypes. The presence of three distinct molecular profiles of T1 is unique and raises the issue as to whether T120 and T121 represent distinct prion strains. To answer this question, brain homogenates from sCJDVV cases harboring each of the three resPrPD profiles, were inoculated to transgenic (Tg) mice expressing the human PrP-129M or PrP-129V genotypes. We found that T120 and T121 were faithfully replicated in Tg129V mice. Electrophoretic profile and incubation period of mice challenged with T121-20 resembled those of mice inoculated with T121 and T120, respectively. As in sCJDVV1, Tg129V mice challenged with T121 and T120 generated virtually undistinguishable histotypes. In Tg129M mice, T121 was not replicated while T120 and T121-20 generated a ~ 21-20 kDa doublet after lengthier incubation periods. On second passage, Tg129M mice incubation periods and regional PrP accumulation significantly differed in T120 and T121-20 challenged mice. Combined, these data indicate that T121 and T120 resPrPD represent distinct human

Published
2021

9. Allelic Interference in Prion Replication Is Modulated by the Convertibility of the Interfering PrPC and Other Host-Specific Factors

Author

Ministerio de Economía y Competitividad (España), CSIC - Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Espinosa Martín, Juan Carlos [0000-0002-6719-9902], Andreoletti, Olivier [0000-0002-7369-6016], Marín-Moreno, Alba [0000-0002-4023-6398], Cassard, Hervé [0000-0001-8651-6179], Prieto, Irene [0000-0001-5900-8419], Huor, Alvina [0000-0002-5598-9958], Torres, Juan María [0000-0003-0443-9232], Espinosa Martín, Juan Carlos, Andréoletti, Olivier, Marín-Moreno, Alba, Lugan, Séverine, Aguilar-Calvo, Patricia, Cassard, Hervé, Lorenzo, Patricia, Douet, Jean-Yves, Villa Díaz, Ana, Aron, Naima, Prieto, Irene, Huor, Alvina, Torres, Juan María, Ministerio de Economía y Competitividad (España), CSIC - Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Espinosa Martín, Juan Carlos [0000-0002-6719-9902], Andreoletti, Olivier [0000-0002-7369-6016], Marín-Moreno, Alba [0000-0002-4023-6398], Cassard, Hervé [0000-0001-8651-6179], Prieto, Irene [0000-0001-5900-8419], Huor, Alvina [0000-0002-5598-9958], Torres, Juan María [0000-0003-0443-9232], Espinosa Martín, Juan Carlos, Andréoletti, Olivier, Marín-Moreno, Alba, Lugan, Séverine, Aguilar-Calvo, Patricia, Cassard, Hervé, Lorenzo, Patricia, Douet, Jean-Yves, Villa Díaz, Ana, Aron, Naima, Prieto, Irene, Huor, Alvina, and Torres, Juan María

Abstract

Early studies in transgenic mouse lines have shown that the coexpression of endogenous murine prion protein (PrPC) and transgenic PrPC from another species either inhibits or allows the propagation of prions, depending on the infecting prion strain and interacting protein species. The way whereby this phenomenon, so-called "interference," is modulated remains to be determined. In this study, different transgenic mouse lines were crossbred to produce mice coexpressing bovine and porcine PrPC, bovine and murine PrPC, or murine and porcine PrPC These animals and their respective hemizygous controls were inoculated with several prion strains from different sources (cattle, mice, and pigs) to examine the effects of the simultaneous presence of PrPC from two different species. Our results indicate interference with the infection process, manifested as extended survival times and reduced attack rates. The interference with the infectious process was reduced or absent when the potentiality interfering PrPC species was efficiently converted by the inoculated agent. However, the propagation of the endogenous murine PrPSc was favored, allowing us to speculate that host-specific factors may disturb the interference caused by the coexpression of an exogenous second PrPC IMPORTANCE Prion propagation can be interfered with by the expression of a second prion protein in the host. In the present study, we investigated prion propagation in a host expressing two different prion protein genes. Our findings indicate that the ability of the second prion protein to interfere with prion propagation is related to the transmissibility of the prion in the host expressing only the interfering prion protein. The interference detected occurs in a prion strain-dependent manner. Interestingly, a bias favoring the propagation of the murine PrP allele has been observed. These results open the door to future studies in order to determine the role of host factors other than the PrP amino acid sequence

Published
2021

10. Classical BSE prions emerge from asymptomatic pigs challenged with atypical/Nor98 scrapie

Author

European Commission, Ministerio de Ciencia e Innovación (España), Marín, Belén [0000-0002-1590-3347], Otero, Alicia [0000-0001-9075-2764], Espinosa Martín, Juan Carlos [0000-0002-6719-9902], Marín-Moreno, Alba [0000-0002-4023-6398], Vidal, Enric [0000-0002-4965-3286], Hedman, Carlos [0000-0002-0827-110X], Pumarola, Martí[0000-0002-0935-7941], Badiola, Juan J [0000-0002-7173-7216], Torres, Juan María [0000-0003-0443-9232], Andréoletti, Olivier [0000-0002-7369-6016], Bolea, Rosa [0000-0002-2746-3932], Marín, Belén, Otero, Alicia, Lugan, Séverine, Espinosa Martín, Juan Carlos, Marín-Moreno, Alba, Vidal, Enric, Hedman, Carlos, Romero, Antonio, Pumarola, Martí, Badiola, Juan J., Torres, Juan María, Andréoletti, Olivier, Bolea, Rosa, European Commission, Ministerio de Ciencia e Innovación (España), Marín, Belén [0000-0002-1590-3347], Otero, Alicia [0000-0001-9075-2764], Espinosa Martín, Juan Carlos [0000-0002-6719-9902], Marín-Moreno, Alba [0000-0002-4023-6398], Vidal, Enric [0000-0002-4965-3286], Hedman, Carlos [0000-0002-0827-110X], Pumarola, Martí[0000-0002-0935-7941], Badiola, Juan J [0000-0002-7173-7216], Torres, Juan María [0000-0003-0443-9232], Andréoletti, Olivier [0000-0002-7369-6016], Bolea, Rosa [0000-0002-2746-3932], Marín, Belén, Otero, Alicia, Lugan, Séverine, Espinosa Martín, Juan Carlos, Marín-Moreno, Alba, Vidal, Enric, Hedman, Carlos, Romero, Antonio, Pumarola, Martí, Badiola, Juan J., Torres, Juan María, Andréoletti, Olivier, and Bolea, Rosa

Abstract

Pigs are susceptible to infection with the classical bovine spongiform encephalopathy (C-BSE) agent following experimental inoculation, and PrPSc accumulation was detected in porcine tissues after the inoculation of certain scrapie and chronic wasting disease isolates. However, a robust transmission barrier has been described in this species and, although they were exposed to C-BSE agent in many European countries, no cases of natural transmissible spongiform encephalopathies (TSE) infections have been reported in pigs. Transmission of atypical scrapie to bovinized mice resulted in the emergence of C-BSE prions. Here, we conducted a study to determine if pigs are susceptible to atypical scrapie. To this end, 12, 8-9-month-old minipigs were intracerebrally inoculated with two atypical scrapie sources. Animals were euthanized between 22- and 72-months post inoculation without clinical signs of TSE. All pigs tested negative for PrPSc accumulation by enzyme immunoassay, immunohistochemistry, western blotting and bioassay in porcine PrP mice. Surprisingly, in vitro protein misfolding cyclic amplification demonstrated the presence of C-BSE prions in different brain areas from seven pigs inoculated with both atypical scrapie isolates. Our results suggest that pigs exposed to atypical scrapie prions could become a reservoir for C-BSE and corroborate that C-BSE prions emerge during interspecies passage of atypical scrapie.

Published
2021

11. Prions from Sporadic Creutzfeldt-Jakob Disease Patients Propagate as Strain Mixtures

Author

European Commission, Food Standards Agency (UK), Ministerio de Economía y Competitividad (España), CSIC - Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Cassard, Hervé [0000-0001-8651-6179], Huor, Alvina [0000-0002-5598-9958], Espinosa Martín, Juan Carlos [0000-0002-6719-9902], Douet, Jean-Yves [0000-0002-0426-4957], Vilette, Didier [0000-0001-8429-9916], Delisle, Marie-Bernadette [0000-0002-8254-7047], Marín-Moreno, Alba [0000-0002-4023-6398], Peran, Patrice [0000-0001-7200-0139], Béringue, V. [0000-0001-6706-5712], Torres, Juan María [0000-0003-0443-9232], Ironside, James W. [0000-0001-5869-2108], Andréoletti, Olivier [0000-0002-7369-6016], Cassard, Hervé, Huor, Alvina, Espinosa Martín, Juan Carlos, Douet, Jean-Yves, Lugan, Séverine, Aron, Naima, Vilette, Didier, Delisle, Marie-Bernadette, Marín-Moreno, Alba, Peran, Patrice, Béringue, V., Torres, Juan María, Ironside, James W., Andréoletti, Olivier, European Commission, Food Standards Agency (UK), Ministerio de Economía y Competitividad (España), CSIC - Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Cassard, Hervé [0000-0001-8651-6179], Huor, Alvina [0000-0002-5598-9958], Espinosa Martín, Juan Carlos [0000-0002-6719-9902], Douet, Jean-Yves [0000-0002-0426-4957], Vilette, Didier [0000-0001-8429-9916], Delisle, Marie-Bernadette [0000-0002-8254-7047], Marín-Moreno, Alba [0000-0002-4023-6398], Peran, Patrice [0000-0001-7200-0139], Béringue, V. [0000-0001-6706-5712], Torres, Juan María [0000-0003-0443-9232], Ironside, James W. [0000-0001-5869-2108], Andréoletti, Olivier [0000-0002-7369-6016], Cassard, Hervé, Huor, Alvina, Espinosa Martín, Juan Carlos, Douet, Jean-Yves, Lugan, Séverine, Aron, Naima, Vilette, Didier, Delisle, Marie-Bernadette, Marín-Moreno, Alba, Peran, Patrice, Béringue, V., Torres, Juan María, Ironside, James W., and Andréoletti, Olivier

Abstract

Sporadic Creutzfeldt-Jakob disease (sCJD) cases are currently classified according to the methionine/valine polymorphism at codon 129 of the PRNP gene and the proteinase K-digested abnormal prion protein (PrPres) isoform identified by Western blotting (type 1 or type 2). Converging evidence led to the view that MM/MV1, VV/MV2, and VV1 and MM2 sCJD cases are caused by distinct prion strains. However, in a significant proportion of sCJD patients, both type 1 and type 2 PrPres were reported to accumulate in the brain, which raised questions about the diversity of sCJD prion strains and the coexistence of two prion strains in the same patient. In this study, a panel of sCJD brain isolates (n = 29) that displayed either a single or mixed type 1/type 2 PrPres were transmitted into human-PrP-expressing mice (tgHu). These bioassays demonstrated that two distinct prion strains (M1CJD and V2CJD) were associated with the development of sCJD in MM1/MV1 and VV2/MV2 patients. However, in about 35% of the investigated VV and MV cases, transmission results were consistent with the presence of both M1CJD and V2CJD strains, including in patients who displayed a "pure" type 1 or type 2 PrPres The use of a highly sensitive prion in vitro amplification technique that specifically probes the V2CJD strain revealed the presence of the V2CJD prion in more than 80% of the investigated isolates, including isolates that propagated as a pure M1CJD strain in tgHu. These results demonstrate that at least two sCJD prion strains can be present in a single patient.IMPORTANCE sCJD occurrence is currently assumed to result from spontaneous and stochastic formation of a misfolded PrP nucleus in the brains of affected patients. This original nucleus then recruits and converts nascent PrPC into PrPSc, leading to the propagation of prions in the patient's brain. Our study demonstrates the coexistence of two prion strains in the brains of a majority of the 23 sCJD patients investigated. The relative propor

Published
2020

12. MicroRNA Alterations in a Tg501 Mouse Model of Prion Disease

Author

Ministerio de Economía y Competitividad (España), Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España), Instituto de Salud Carlos III, European Commission, CSIC - Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Gobierno de Aragón, Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas (España), Toivonen, Janne Markus [0000-0002-7243-1737], Sánz-Rubio, David [0000-0002-5228-248X], López-Pérez, Óscar [0000-0003-2454-2114], Marín-Moreno, Alba [0000-0002-4023-6398], Bolea, Rosa [0000-0002-2746-3932], Osta, Rosario [0000-0001-5687-6704], Badiola, Juan J. [0000-0002-7173-7216], Espinosa Martín, Juan Carlos [0000-0002-6719-9902], Torres, Juan María [0000-0003-0443-9232], Martín-Burriel, Inmaculada [0000-0001-6016-4726], Toivonen, Janne Markus, Sánz-Rubio, David, López-Pérez, Óscar, Marín-Moreno, Alba, Bolea, Rosa, Osta, Rosario, Badiola, Juan J., Zaragoza, P., Espinosa Martín, Juan Carlos, Torres, Juan María, Martín-Burriel, Inmaculada, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España), Instituto de Salud Carlos III, European Commission, CSIC - Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Gobierno de Aragón, Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas (España), Toivonen, Janne Markus [0000-0002-7243-1737], Sánz-Rubio, David [0000-0002-5228-248X], López-Pérez, Óscar [0000-0003-2454-2114], Marín-Moreno, Alba [0000-0002-4023-6398], Bolea, Rosa [0000-0002-2746-3932], Osta, Rosario [0000-0001-5687-6704], Badiola, Juan J. [0000-0002-7173-7216], Espinosa Martín, Juan Carlos [0000-0002-6719-9902], Torres, Juan María [0000-0003-0443-9232], Martín-Burriel, Inmaculada [0000-0001-6016-4726], Toivonen, Janne Markus, Sánz-Rubio, David, López-Pérez, Óscar, Marín-Moreno, Alba, Bolea, Rosa, Osta, Rosario, Badiola, Juan J., Zaragoza, P., Espinosa Martín, Juan Carlos, Torres, Juan María, and Martín-Burriel, Inmaculada

Abstract

MicroRNAs (miRNAs) may contribute to the development and pathology of many neurodegenerative diseases, including prion diseases. They are also promising biomarker candidates due to their stability in body fluids. We investigated miRNA alterations in a Tg501 mouse model of prion diseases that expresses a transgene encoding the goat prion protein (PRNP). Tg501 mice intracranially inoculated with mouse-adapted goat scrapie were compared with age-matched, mock inoculated controls in preclinical and clinical stages. Small RNA sequencing from the cervical spinal cord indicated that miR-223-3p, miR-151-3p, and miR-144-5p were dysregulated in scrapie-inoculated animals before the onset of symptoms. In clinical-stage animals, 23 significant miRNA alterations were found. These miRNAs were predicted to modify the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways including prion disease, extracellular matrix interactions, glutaminergic synapse, axon guidance, and transforming growth factor-beta signaling. MicroRNAs miR-146a-5p (up in cervical spinal cord) and miR-342-3p (down in cervical spinal cord, cerebellum and plasma), both indicated in neurodegenerative diseases earlier, were verified by quantitative real-time polymerase chain reaction (qRT-PCR). Minimal changes observed before the disease onset suggests that most miRNA alterations observed here are driven by advanced prion-associated pathology, possibly limiting their use as diagnostic markers. However, the results encourage further mechanistic studies on miRNA-regulated pathways involved in these neurodegenerative conditions.

Published
2020

13. Characterization of goat prions demonstrates geographical variation of scrapie strains in Europe and reveals the composite nature of prion strains

Author

European Commission, Ministry of Agriculture, Nature and Food Quality (The Netherlands), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), CSIC - Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Ministerio de Economía y Competitividad (España), Nonno, Romolo [0000-0001-7556-1564], Marín-Moreno, Alba [0000-0002-4023-6398], Espinosa Martín, Juan Carlos [0000-0002-6719-9902], Fast, C. [0000-0002-7341-7873], Van Keulen, Lucien [0000-0002-8645-5190], Spiropoulos, J. [0000-0003-0119-8920], Lantier, Isabelle [0000-0003-1250-767X], Andréoletti, Olivier [0000-0002-7369-6016], Pirisinu, Laura [0000-0002-6548-8225], di Bari, Michele [0000-0003-0943-6823], Sklaviadis, T. [0000-0002-0246-3100], Acutis, Pier Luigi [0000-0003-4814-2924], Acin, Cristina [0000-0001-5105-6133], Bossers, A. [0000-0002-6586-717X], Vaccari, Gabriel [0000-0003-0215-3521], Chiappini, Barbara [0000-0002-5260-5285], Lantier, Frederic [0000-0001-5896-330X], Groschup, M. H. [0000-0003-0215-185X], Agrimi, Umberto [0000-0001-7828-0186], Torres, Juan María [0000-0003-0443-9232], Langeveld, J. [0000-0002-4165-3230], Nonno, Romolo, Marín-Moreno, Alba, Espinosa Martín, Juan Carlos, Fast, C., Van Keulen, Lucien, Spiropoulos, J., Lantier, Isabelle, Andréoletti, Olivier, Pirisinu, Laura, di Bari, Michele, Aguilar-Calvo, Patricia, Sklaviadis, T., Papasavva-Stylianou, Penelope, Acutis, Pier Luigi, Acin, Cristina, Bossers, A., Jacobs, Jorge G., Vaccari, Gabriel, D'Agostino, Claudia, Chiappini, Barbara, Lantier, Frederic, Groschup, M. H., Agrimi, Umberto, Torres, Juan María, Langeveld, J., European Commission, Ministry of Agriculture, Nature and Food Quality (The Netherlands), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), CSIC - Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Ministerio de Economía y Competitividad (España), Nonno, Romolo [0000-0001-7556-1564], Marín-Moreno, Alba [0000-0002-4023-6398], Espinosa Martín, Juan Carlos [0000-0002-6719-9902], Fast, C. [0000-0002-7341-7873], Van Keulen, Lucien [0000-0002-8645-5190], Spiropoulos, J. [0000-0003-0119-8920], Lantier, Isabelle [0000-0003-1250-767X], Andréoletti, Olivier [0000-0002-7369-6016], Pirisinu, Laura [0000-0002-6548-8225], di Bari, Michele [0000-0003-0943-6823], Sklaviadis, T. [0000-0002-0246-3100], Acutis, Pier Luigi [0000-0003-4814-2924], Acin, Cristina [0000-0001-5105-6133], Bossers, A. [0000-0002-6586-717X], Vaccari, Gabriel [0000-0003-0215-3521], Chiappini, Barbara [0000-0002-5260-5285], Lantier, Frederic [0000-0001-5896-330X], Groschup, M. H. [0000-0003-0215-185X], Agrimi, Umberto [0000-0001-7828-0186], Torres, Juan María [0000-0003-0443-9232], Langeveld, J. [0000-0002-4165-3230], Nonno, Romolo, Marín-Moreno, Alba, Espinosa Martín, Juan Carlos, Fast, C., Van Keulen, Lucien, Spiropoulos, J., Lantier, Isabelle, Andréoletti, Olivier, Pirisinu, Laura, di Bari, Michele, Aguilar-Calvo, Patricia, Sklaviadis, T., Papasavva-Stylianou, Penelope, Acutis, Pier Luigi, Acin, Cristina, Bossers, A., Jacobs, Jorge G., Vaccari, Gabriel, D'Agostino, Claudia, Chiappini, Barbara, Lantier, Frederic, Groschup, M. H., Agrimi, Umberto, Torres, Juan María, and Langeveld, J.

Abstract

Bovine Spongiform Encephalopathy (BSE) is the only animal prion which has been recognized as a zoonotic agent so far. The identification of BSE in two goats raised the need to reliably identify BSE in small ruminants. However, our understanding of scrapie strain diversity in small ruminants remains ill-defined, thus limiting the accuracy of BSE surveillance and spreading fear that BSE might lurk unrecognized in goats. We investigated prion strain diversity in a large panel of European goats by a novel experimental approach that, instead of assessing the neuropathological profile after serial transmissions in a single animal model, was based on the direct interaction of prion isolates with several recipient rodent models expressing small ruminants or heterologous prion proteins. The findings show that the biological properties of scrapie isolates display different patterns of geographical distribution in Europe and suggest that goat BSE could be reliably discriminated from a wide range of biologically and geographically diverse goat prion isolates. Finally, most field prion isolates showed composite strain features, with discrete strain components or sub-strains being present in different proportions in individual goats or tissues. This has important implications for understanding the nature and evolution of scrapie strains and their transmissibility to other species, including humans.

Published
2020

14. Erratum to: Porcine Prion Protein as a Paradigm of Limited Susceptibility to Prion Strain Propagation

Author

Espinosa Martín, Juan Carlos [0000-0002-6719-9902], Marín-Moreno, Alba (0000-0002-4023-6398), Benestad, Sylvie L (0000-0002-3011-0484), Andreoletti, Olivier (0000-0002-7369-6016), Torres, Juan María (0000-0003-0443-9232), Espinosa Martín, Juan Carlos, Marín-Moreno, Alba, Aguilar-Calvo, Patricia, Benestad, Sylvie L., Andréoletti, Olivier, Torres, Juan María, Espinosa Martín, Juan Carlos [0000-0002-6719-9902], Marín-Moreno, Alba (0000-0002-4023-6398), Benestad, Sylvie L (0000-0002-3011-0484), Andreoletti, Olivier (0000-0002-7369-6016), Torres, Juan María (0000-0003-0443-9232), Espinosa Martín, Juan Carlos, Marín-Moreno, Alba, Aguilar-Calvo, Patricia, Benestad, Sylvie L., Andréoletti, Olivier, and Torres, Juan María

Abstract

In "Porcine Prion Protein as a Paradigm of Limited Susceptibility to Prion Strain Propagation" by Espinosa et al. [J Infect Dis, doi:10.1093/infdis/jiz646], there was an error in Figure 2 and the footnote corresponding to Supplementary Figure 1 was missing. These have been corrected in the original article. (Figure Presented)., This is a correction to: The Journal of Infectious Diseases, Volume 223, Issue 6, 15 March 2021, Pages 1103–1112, https://doi.org/10.1093/infdis/jiz646

Published
2020

15. Transgenic mouse models for the study of prion diseases

Author

Marín-Moreno, Alba [0000-0002-4023-6398], Espinosa Martín, Juan Carlos [0000-0002-6719-9902], Torres, Juan María [0000-0003-0443-9232], Marín-Moreno, Alba, Espinosa Martín, Juan Carlos, Torres, Juan María, Marín-Moreno, Alba [0000-0002-4023-6398], Espinosa Martín, Juan Carlos [0000-0002-6719-9902], Torres, Juan María [0000-0003-0443-9232], Marín-Moreno, Alba, Espinosa Martín, Juan Carlos, and Torres, Juan María

Abstract

Prions are unique agents that challenge the molecular biology dogma by transmitting information on the protein level. They cause neurodegenerative diseases that lack of any cure or treatment called transmissible spongiform encephalopathies. The function of the normal form of the prion protein, the exact mechanism of prion propagation between species as well as at the cellular level and neuron degeneration remains elusive. However, great amount of information known for all these aspects has been achieved thanks to the use of animal models and more precisely to transgenic mouse models. In this chapter, the main contributions of these powerful research tools in the prion field are revised.

Published
2020

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