RT Journal Article
T1 iPS Cell Cultures from a Gerstmann-Sträussler-Scheinker Patient with the Y218N PRNP Mutation Recapitulate tau Pathology.
A1 Matamoros-Angles, Andreu
A1 Gayosso, Lucía Mayela
A1 Richaud-Patin, Yvonne
A1 di Domenico, Angelique
A1 Vergara, Cristina
A1 Hervera, Arnau
A1 Sousa, Amaya
A1 Fernández-Borges, Natalia
A1 Consiglio, Antonella
A1 Gavín, Rosalina
A1 López de Maturana, Rakel
A1 Ferrer, Isidro
A1 López de Munain, Adolfo
A1 Raya, Ángel
A1 Castilla, Joaquín
A1 Sánchez-Pernaute, Rosario
A1 Del Río, José Antonio
K1 Cellular prion protein
K1 Gerstmann-Sträussler-Scheinker
K1 Induced pluripotent stem cells
K1 Tau
AB Gerstmann-Sträussler-Scheinker (GSS) syndrome is a fatal autosomal dominant neurodegenerative prionopathy clinically characterized by ataxia, spastic paraparesis, extrapyramidal signs and dementia. In some GSS familiar cases carrying point mutations in the PRNP gene, patients also showed comorbid tauopathy leading to mixed pathologies. In this study we developed an induced pluripotent stem (iPS) cell model derived from fibroblasts of a GSS patient harboring the Y218N PRNP mutation, as well as an age-matched healthy control. This particular PRNP mutation is unique with very few described cases. One of the cases presented neurofibrillary degeneration with relevant Tau hyperphosphorylation. Y218N iPS-derived cultures showed relevant astrogliosis, increased phospho-Tau, altered microtubule-associated transport and cell death. However, they failed to generate proteinase K-resistant prion. In this study we set out to test, for the first time, whether iPS cell-derived neurons could be used to investigate the appearance of disease-related phenotypes (i.e, tauopathy) identified in the GSS patient.
YR 2017
FD 2017-05-02
LK http://hdl.handle.net/10668/11161
UL http://hdl.handle.net/10668/11161
LA en
DS RISalud
RD Apr 7, 2025