iPS Cell Cultures from a Gerstmann-Sträussler-Scheinker Patient with the Y218N PRNP Mutation Recapitulate tau Pathology
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 ta...
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| Veröffentlicht in: | Molecular neurobiology 2018-04, Vol.55 (4), p.3033-3048 |
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| creator | Matamoros-Angles, Andreu Gayosso, Lucía Mayela Richaud-Patin, Yvonne di Domenico, Angelique Vergara, Cristina Hervera, Arnau Sousa, Amaya Fernández-Borges, Natalia Consiglio, Antonella Gavín, Rosalina López de Maturana, Rakel Ferrer, Isidro López de Munain, Adolfo Raya, Ángel Castilla, Joaquín Sánchez-Pernaute, Rosario del Río, José Antonio |
| description | 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. |
| doi_str_mv | 10.1007/s12035-017-0506-6 |
| format | Article |
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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.</description><identifier>ISSN: 0893-7648</identifier><identifier>EISSN: 1559-1182</identifier><identifier>DOI: 10.1007/s12035-017-0506-6</identifier><identifier>PMID: 28466265</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Astrocytes - metabolism ; Astrocytes - pathology ; Ataxia ; Base Sequence ; Biomedical and Life Sciences ; Biomedicine ; Brain - pathology ; Cell Biology ; Cell death ; Cell Differentiation ; Cells, Cultured ; Dementia disorders ; Endopeptidase K ; Extrapyramidal system ; Female ; Fibroblasts ; Gerstmann-Straussler-Scheinker Disease - genetics ; Gerstmann-Straussler-Scheinker Disease - pathology ; Gliosis ; Gliosis - pathology ; Hereditary spastic paraplegia ; Humans ; Induced Pluripotent Stem Cells - metabolism ; Induced Pluripotent Stem Cells - pathology ; Middle Aged ; Mitochondria - metabolism ; Mutation ; Mutation - genetics ; Neurobiology ; Neurodegeneration ; Neurodegenerative diseases ; Neurology ; Neurons - metabolism ; Neurons - pathology ; Neurosciences ; Phosphorylation ; Pluripotency ; Prion protein ; Prion Proteins - genetics ; Proteinase ; Tau protein ; tau Proteins - metabolism</subject><ispartof>Molecular neurobiology, 2018-04, Vol.55 (4), p.3033-3048</ispartof><rights>The Author(s) 2017</rights><rights>Molecular Neurobiology is a copyright of Springer, (2017). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c470t-830c3d8b24f791def25eede12e2c43049d0d393d6801d2d92d9df36c0d3a199f3</citedby><cites>FETCH-LOGICAL-c470t-830c3d8b24f791def25eede12e2c43049d0d393d6801d2d92d9df36c0d3a199f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12035-017-0506-6$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12035-017-0506-6$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28466265$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Matamoros-Angles, Andreu</creatorcontrib><creatorcontrib>Gayosso, Lucía Mayela</creatorcontrib><creatorcontrib>Richaud-Patin, Yvonne</creatorcontrib><creatorcontrib>di Domenico, Angelique</creatorcontrib><creatorcontrib>Vergara, Cristina</creatorcontrib><creatorcontrib>Hervera, Arnau</creatorcontrib><creatorcontrib>Sousa, Amaya</creatorcontrib><creatorcontrib>Fernández-Borges, Natalia</creatorcontrib><creatorcontrib>Consiglio, Antonella</creatorcontrib><creatorcontrib>Gavín, Rosalina</creatorcontrib><creatorcontrib>López de Maturana, Rakel</creatorcontrib><creatorcontrib>Ferrer, Isidro</creatorcontrib><creatorcontrib>López de Munain, Adolfo</creatorcontrib><creatorcontrib>Raya, Ángel</creatorcontrib><creatorcontrib>Castilla, Joaquín</creatorcontrib><creatorcontrib>Sánchez-Pernaute, Rosario</creatorcontrib><creatorcontrib>del Río, José Antonio</creatorcontrib><title>iPS Cell Cultures from a Gerstmann-Sträussler-Scheinker Patient with the Y218N PRNP Mutation Recapitulate tau Pathology</title><title>Molecular neurobiology</title><addtitle>Mol Neurobiol</addtitle><addtitle>Mol Neurobiol</addtitle><description>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.</description><subject>Astrocytes - metabolism</subject><subject>Astrocytes - pathology</subject><subject>Ataxia</subject><subject>Base Sequence</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Brain - pathology</subject><subject>Cell Biology</subject><subject>Cell death</subject><subject>Cell Differentiation</subject><subject>Cells, Cultured</subject><subject>Dementia disorders</subject><subject>Endopeptidase K</subject><subject>Extrapyramidal system</subject><subject>Female</subject><subject>Fibroblasts</subject><subject>Gerstmann-Straussler-Scheinker Disease - genetics</subject><subject>Gerstmann-Straussler-Scheinker Disease - pathology</subject><subject>Gliosis</subject><subject>Gliosis - pathology</subject><subject>Hereditary spastic paraplegia</subject><subject>Humans</subject><subject>Induced Pluripotent Stem Cells - metabolism</subject><subject>Induced Pluripotent Stem Cells - pathology</subject><subject>Middle Aged</subject><subject>Mitochondria - metabolism</subject><subject>Mutation</subject><subject>Mutation - genetics</subject><subject>Neurobiology</subject><subject>Neurodegeneration</subject><subject>Neurodegenerative diseases</subject><subject>Neurology</subject><subject>Neurons - metabolism</subject><subject>Neurons - pathology</subject><subject>Neurosciences</subject><subject>Phosphorylation</subject><subject>Pluripotency</subject><subject>Prion protein</subject><subject>Prion Proteins - genetics</subject><subject>Proteinase</subject><subject>Tau protein</subject><subject>tau Proteins - metabolism</subject><issn>0893-7648</issn><issn>1559-1182</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kd2KFDEQhYMo7rj6AN5IwBtvopV0pzu5EWTQVVjXYUcvvArZTvV0rz2dMT_qvo9v4ouZYdb1B4RAIOfUqap8hDzk8JQDtM8iF1BJBrxlIKFhzS2y4FJqxrkSt8kClK5Y29TqiNyL8RJACA7tXXIkVN00opEL8m1crekSp4ku85RywEj74LfU0hMMMW3tPLN1Cj--5xgnDGzdDTjOnzDQlU0jzol-HdNA04D0o-DqjK7Oz1b0bU5F9TM9x87uxpQnm5Amm_dVg5_85uo-udPbKeKD6_uYfHj18v3yNTt9d_Jm-eKUdXULiakKusqpC1H3reYOeyERHXKBoqsrqLUDV-nKNQq4E06X4_qq6cqr5Vr31TF5fsjd5Ystuq6MHOxkdmHc2nBlvB3N38o8DmbjvxipaiFBl4An1wHBf84Yk9mOsSs_Zmf0ORqudK25LP2L9fE_1kufw1zWMwIKGAGyboqLH1xd8DEG7G-G4WD2XM2BqylczZ6r2dc8-nOLm4pfIItBHAyxSPMGw-_W_0_9CYRZr1s</recordid><startdate>20180401</startdate><enddate>20180401</enddate><creator>Matamoros-Angles, Andreu</creator><creator>Gayosso, Lucía Mayela</creator><creator>Richaud-Patin, Yvonne</creator><creator>di Domenico, Angelique</creator><creator>Vergara, Cristina</creator><creator>Hervera, Arnau</creator><creator>Sousa, Amaya</creator><creator>Fernández-Borges, Natalia</creator><creator>Consiglio, Antonella</creator><creator>Gavín, Rosalina</creator><creator>López de Maturana, Rakel</creator><creator>Ferrer, Isidro</creator><creator>López de Munain, Adolfo</creator><creator>Raya, Ángel</creator><creator>Castilla, Joaquín</creator><creator>Sánchez-Pernaute, Rosario</creator><creator>del Río, José Antonio</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QR</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88G</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M2P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20180401</creationdate><title>iPS Cell Cultures from a Gerstmann-Sträussler-Scheinker Patient with the Y218N PRNP Mutation Recapitulate tau Pathology</title><author>Matamoros-Angles, Andreu ; Gayosso, Lucía Mayela ; Richaud-Patin, Yvonne ; di Domenico, Angelique ; Vergara, Cristina ; Hervera, Arnau ; Sousa, Amaya ; Fernández-Borges, Natalia ; Consiglio, Antonella ; Gavín, Rosalina ; López de Maturana, Rakel ; Ferrer, Isidro ; López de Munain, Adolfo ; Raya, Ángel ; Castilla, Joaquín ; Sánchez-Pernaute, Rosario ; del Río, José Antonio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c470t-830c3d8b24f791def25eede12e2c43049d0d393d6801d2d92d9df36c0d3a199f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Astrocytes - metabolism</topic><topic>Astrocytes - pathology</topic><topic>Ataxia</topic><topic>Base Sequence</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Brain - pathology</topic><topic>Cell Biology</topic><topic>Cell death</topic><topic>Cell Differentiation</topic><topic>Cells, Cultured</topic><topic>Dementia disorders</topic><topic>Endopeptidase K</topic><topic>Extrapyramidal system</topic><topic>Female</topic><topic>Fibroblasts</topic><topic>Gerstmann-Straussler-Scheinker Disease - genetics</topic><topic>Gerstmann-Straussler-Scheinker Disease - pathology</topic><topic>Gliosis</topic><topic>Gliosis - pathology</topic><topic>Hereditary spastic paraplegia</topic><topic>Humans</topic><topic>Induced Pluripotent Stem Cells - metabolism</topic><topic>Induced Pluripotent Stem Cells - pathology</topic><topic>Middle Aged</topic><topic>Mitochondria - metabolism</topic><topic>Mutation</topic><topic>Mutation - genetics</topic><topic>Neurobiology</topic><topic>Neurodegeneration</topic><topic>Neurodegenerative diseases</topic><topic>Neurology</topic><topic>Neurons - metabolism</topic><topic>Neurons - pathology</topic><topic>Neurosciences</topic><topic>Phosphorylation</topic><topic>Pluripotency</topic><topic>Prion protein</topic><topic>Prion Proteins - genetics</topic><topic>Proteinase</topic><topic>Tau protein</topic><topic>tau Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Matamoros-Angles, Andreu</creatorcontrib><creatorcontrib>Gayosso, Lucía Mayela</creatorcontrib><creatorcontrib>Richaud-Patin, Yvonne</creatorcontrib><creatorcontrib>di Domenico, Angelique</creatorcontrib><creatorcontrib>Vergara, Cristina</creatorcontrib><creatorcontrib>Hervera, Arnau</creatorcontrib><creatorcontrib>Sousa, Amaya</creatorcontrib><creatorcontrib>Fernández-Borges, Natalia</creatorcontrib><creatorcontrib>Consiglio, Antonella</creatorcontrib><creatorcontrib>Gavín, Rosalina</creatorcontrib><creatorcontrib>López de Maturana, Rakel</creatorcontrib><creatorcontrib>Ferrer, Isidro</creatorcontrib><creatorcontrib>López de Munain, Adolfo</creatorcontrib><creatorcontrib>Raya, Ángel</creatorcontrib><creatorcontrib>Castilla, Joaquín</creatorcontrib><creatorcontrib>Sánchez-Pernaute, Rosario</creatorcontrib><creatorcontrib>del Río, José Antonio</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Psychology Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular neurobiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Matamoros-Angles, Andreu</au><au>Gayosso, Lucía Mayela</au><au>Richaud-Patin, Yvonne</au><au>di Domenico, Angelique</au><au>Vergara, Cristina</au><au>Hervera, Arnau</au><au>Sousa, Amaya</au><au>Fernández-Borges, Natalia</au><au>Consiglio, Antonella</au><au>Gavín, Rosalina</au><au>López de Maturana, Rakel</au><au>Ferrer, Isidro</au><au>López de Munain, Adolfo</au><au>Raya, Ángel</au><au>Castilla, Joaquín</au><au>Sánchez-Pernaute, Rosario</au><au>del Río, José Antonio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>iPS Cell Cultures from a Gerstmann-Sträussler-Scheinker Patient with the Y218N PRNP Mutation Recapitulate tau Pathology</atitle><jtitle>Molecular neurobiology</jtitle><stitle>Mol Neurobiol</stitle><addtitle>Mol Neurobiol</addtitle><date>2018-04-01</date><risdate>2018</risdate><volume>55</volume><issue>4</issue><spage>3033</spage><epage>3048</epage><pages>3033-3048</pages><issn>0893-7648</issn><eissn>1559-1182</eissn><abstract>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.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>28466265</pmid><doi>10.1007/s12035-017-0506-6</doi><tpages>16</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Molecular neurobiology, 2018-04, Vol.55 (4), p.3033-3048 |
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| subjects | Astrocytes - metabolism Astrocytes - pathology Ataxia Base Sequence Biomedical and Life Sciences Biomedicine Brain - pathology Cell Biology Cell death Cell Differentiation Cells, Cultured Dementia disorders Endopeptidase K Extrapyramidal system Female Fibroblasts Gerstmann-Straussler-Scheinker Disease - genetics Gerstmann-Straussler-Scheinker Disease - pathology Gliosis Gliosis - pathology Hereditary spastic paraplegia Humans Induced Pluripotent Stem Cells - metabolism Induced Pluripotent Stem Cells - pathology Middle Aged Mitochondria - metabolism Mutation Mutation - genetics Neurobiology Neurodegeneration Neurodegenerative diseases Neurology Neurons - metabolism Neurons - pathology Neurosciences Phosphorylation Pluripotency Prion protein Prion Proteins - genetics Proteinase Tau protein tau Proteins - metabolism |
| title | iPS Cell Cultures from a Gerstmann-Sträussler-Scheinker Patient with the Y218N PRNP Mutation Recapitulate tau Pathology |
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