期刊
MOLECULAR NEUROBIOLOGY
卷 55, 期 4, 页码 3033-3048出版社
HUMANA PRESS INC
DOI: 10.1007/s12035-017-0506-6
关键词
Gerstmann-Straussler-Scheinker; Induced pluripotent stem cells; Tau; Cellular prion protein
资金
- Spanish Ministry of Economy, Industry and Competitiveness (MINECO) [BFU2015-67777-R]
- Spanish prion network (Prionet Spain) [AGL2015-71764-REDT]
- Generalitat de Catalunya [SGR2014-1218]
- CIBERNED [PI2014/02-4, PI2016/02]
- La Caixa Obra Social Foundation
- La Marato de TV3
- Joint Program in Neurodegenerative Diseases (DAMNDPATHS) [AC14/00021]
- MINECO [AGL2015-65046-C2-1-R, SAF2015-69706-R, BFU2013-49157-P]
- EiTB Maratoia (BioEF) [BIO12/AL/004]
- Instituto de Salud Carlos III/FEDER [TerCel RD16/0011/0024, PIE14/00061]
- AGAUR [2014-SGR-1460]
- Fundacio La Marato de TV3 [201534-30]
- CERCA Programme/Generalitat de Catalunya
- Fondo de Investigaciones Sanitarias (Instituto de Salud Carlos III)
- FEDER funds/European Regional Development Fund (ERDF) - a way to build Europe [PIE14/00034, PI14/00757]
- European Research Council (ERC) [311736- PD-HUMMODEL]
- Fondo de Investigaciones Sanitarias (Instituto de Salud Carlos III) [PI14/00436]
- Joint Program in Neurodegenerative Diseases (DEMTEST)
- Fundacion Tatiana Perez de Guzman el Bueno
- CONACYT fellowship (Mexico) [CVU 357631]
- RETICTerCel grant from MINECO
Gerstmann-Straussler-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.
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