Patricia Piñeiro
ppineiro
Patricia Piñeiro
LABORATORY TECHNICIAN
Prion Research Lab
Address: Bizkaia Science and Technology Park, building 502, Derio (Bizkaia)

Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative disorders affecting both humans and animals. TSEs can be of genetic, sporadic or infectious origin. The infectious agent associated with TSEs, termed prion, appears to consist of a single protein, an abnormal conformer (PrPSc) of a natural host protein (PrPC), which propagates by converting host PrPC into a replica of itself. One of the characteristics of prions is their ability to infect some species and not others. This phenomenon is known as transmission barrier. Interestingly, prions occur in the form of different strains that show distinct biological and physicochemical properties, even though they are encoded by PrP with the same amino acid sequence, albeit in presumably different conformations. In general, the transmission barrier is expressed by an incomplete attack rate and long incubation times (time from the animal inoculation until the onset of the clinical signs) which become shorter after serial inoculation passages. Compelling evidence indicates that the transmission barriers are closely related to differences in PrP amino acid sequences between the donor and recipients of infection, as well as the prion strain conformation. Unfortunately, the molecular basis of the transmission barrier phenomenon and its relationship to prion strain conformations is currently unknown and we cannot predict the degree of a species barrier simply by comparing the prion proteins from two species.

We have conducted a series of experiments using the Protein Misfolding Cyclic Amplification (PMCA) technique that mimics in vitro some of the fundamental steps involved in prion replication in vivo, albeit with accelerated kinetics. The in vitro generated prions possess key prion features, i.e., they are infectious in vivo and maintain their strain specificity. We have used PMCA to efficiently replicate a variety of prion strains from, among others, mice, hamsters, bank voles, deer, cattle, sheep, and humans. The correlation between in vivo data and our in vitro results suggest that PMCA is a valuable tool for assessing the strength of the transmission barriers between diverse species and for different prion strains; we are using the method to determine which amino acids in the PrPC sequence contribute to the strength of the transmission barrier. These studies are proving very useful in evaluating the potential risks to humans and animals, of not only established prion strains, but also new (atypical) strains. For example, while classical sheep scrapie is unable to cross the human transmission barrier in vitro, bovine spongiform encephalopathy (BSE) propagated in sheep does so efficiently. In addition, we have also generated prions that are infectious to species hitherto considered to be resistant to prion disease.

http://www.asociacioncjd.org/

Latest Publications

Description of the first Spanish case of Gerstmann-Straussler-Scheinker disease with A117V variant: clinical, histopathological and biochemical characterization

Erana, H;San Millan, B;Diaz-Dominguez, CM;Charco, JM;Rodriguez, R;Vieitez, I;Pereda, A;Yanez, R;Geijo, M;Navarro, C;de Nanclares, GP;Teijeira, S;Castilla, J

JOURNAL OF NEUROLOGY

2022-03-16

Biosemiotics comprehension of PrP code and prion disease

Coca, JR;Erana, H;Castilla, J

BIOSYSTEMS

2021-12-01

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

Ximelis, T;Marin-Moreno, A;Espinosa, JC;Erana, H;Charco, JM;Hernandez, I;Riveira, C;Alcolea, D;Gonzalez-Roca, E;Aldecoa, I;Molina-Porcel, L;Parchi, P;Rossi, M;Castilla, J;Ruiz-Garcia, R;Gelpi, ...

ALZHEIMERS RESEARCH & THERAPY

2021-10-18

Cerebrospinal Fluid and Plasma Small Extracellular Vesicles and miRNAs as Biomarkers for Prion Diseases

Lopez-Perez, O;Sanz-Rubio, D;Hernaiz, A;Betancor, M;Otero, A;Castilla, J;Andreoletti, O;Badiola, JJ;Zaragoza, P;Bolea, R;Toivonen, JM;Martin-Burriel, I

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

2021-07-01

Sporadic Creutzfeldt-Jakob disease with extremely long 14-year survival period

Kortazar-Zubizarreta, I;Ruiz-Onandi, R;Pereda, A;Vado, Y;Gonzalez-Chinchon, G;Erana, H;de Nanclares, GP;Castilla, J

EUROPEAN JOURNAL OF NEUROLOGY

2021-06-26

Improving the Pharmacological Properties of Ciclopirox for Its Use in Congenital Erythropoietic Porphyria

Bernardo-Seisdedos, G;Charco, JM;SanJuan, I;Garcia-Martinez, S;Urquiza, P;Erana, H;Castilla, J;Millet, O

JOURNAL OF PERSONALIZED MEDICINE

2021-06-01

Detection of chronic wasting disease in mule and white-tailed deer by RT-QuIC analysis of outer ear

Ferreira, NC;Charco, JM;Plagenz, J;Orru, CD;Denkers, ND;Metrick, MA;Hughson, AG;Griffin, KA;Race, B;Hoover, EA;Castilla, J;Nichols, TA;Miller, MW;Caughey, B

SCIENTIFIC REPORTS

2021-04-08

Prion-Associated Neurodegeneration Causes Both Endoplasmic Reticulum Stress and Proteasome Impairment in a Murine Model of Spontaneous Disease

Otero, A;Betancor, M;Erana, H;Borges, NF;Lucas, JJ;Badiola, JJ;Castilla, J;Bolea, R

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

2021-01-01

A Novel, Reliable and Highly Versatile Method to Evaluate Different Prion Decontamination Procedures

Erana, H;Perez-Castro, MA;Garcia-Martinez, S;Charco, JM;Lopez-Moreno, R;Diaz-Dominguez, CM;Barrio, T;Gonzalez-Miranda, E;Castilla, J

FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY

2020-10-29

Autoantibodies against the prion protein in individuals with PRNP mutations

Frontzek, K;Carta, M;Losa, M;Epskamp, M;Meisl, G;Anane, A;Brandel, JP;Camenisch, U;Castilla, J;Haik, S;Knowles, T;Lindner, E;Lutterotti, A;Minikel, EV;Roiter, I;Safar, JG;Sanchez-Valle, R;Zakova, ...

NEUROLOGY

2020-10-06