Using Human iPSC-Derived Neurons to Model TAU Aggregation.
Alzheimer's disease and frontotemporal dementia are amongst the most common forms of dementia characterized by the formation and deposition of abnormal TAU in the brain. In order to develop a translational human TAU aggregation model suitable for screening, we transduced TAU harboring the pro-a...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4697850?pdf=render |
| _version_ | 1819123613399252992 |
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| author | An Verheyen Annick Diels Joyce Dijkmans Tutu Oyelami Giulia Meneghello Liesbeth Mertens Sofie Versweyveld Marianne Borgers Arjan Buist Pieter Peeters Miroslav Cik |
| author_facet | An Verheyen Annick Diels Joyce Dijkmans Tutu Oyelami Giulia Meneghello Liesbeth Mertens Sofie Versweyveld Marianne Borgers Arjan Buist Pieter Peeters Miroslav Cik |
| author_sort | An Verheyen |
| collection | DOAJ |
| description | Alzheimer's disease and frontotemporal dementia are amongst the most common forms of dementia characterized by the formation and deposition of abnormal TAU in the brain. In order to develop a translational human TAU aggregation model suitable for screening, we transduced TAU harboring the pro-aggregating P301L mutation into control hiPSC-derived neural progenitor cells followed by differentiation into cortical neurons. TAU aggregation and phosphorylation was quantified using AlphaLISA technology. Although no spontaneous aggregation was observed upon expressing TAU-P301L in neurons, seeding with preformed aggregates consisting of the TAU-microtubule binding repeat domain triggered robust TAU aggregation and hyperphosphorylation already after 2 weeks, without affecting general cell health. To validate our model, activity of two autophagy inducers was tested. Both rapamycin and trehalose significantly reduced TAU aggregation levels suggesting that iPSC-derived neurons allow for the generation of a biologically relevant human Tauopathy model, highly suitable to screen for compounds that modulate TAU aggregation. |
| first_indexed | 2024-12-22T07:11:08Z |
| format | Article |
| id | doaj.art-ad1c82f617ec4f259558c47b23bbe4b7 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T07:11:08Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-ad1c82f617ec4f259558c47b23bbe4b72022-12-21T18:34:31ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011012e014612710.1371/journal.pone.0146127Using Human iPSC-Derived Neurons to Model TAU Aggregation.An VerheyenAnnick DielsJoyce DijkmansTutu OyelamiGiulia MeneghelloLiesbeth MertensSofie VersweyveldMarianne BorgersArjan BuistPieter PeetersMiroslav CikAlzheimer's disease and frontotemporal dementia are amongst the most common forms of dementia characterized by the formation and deposition of abnormal TAU in the brain. In order to develop a translational human TAU aggregation model suitable for screening, we transduced TAU harboring the pro-aggregating P301L mutation into control hiPSC-derived neural progenitor cells followed by differentiation into cortical neurons. TAU aggregation and phosphorylation was quantified using AlphaLISA technology. Although no spontaneous aggregation was observed upon expressing TAU-P301L in neurons, seeding with preformed aggregates consisting of the TAU-microtubule binding repeat domain triggered robust TAU aggregation and hyperphosphorylation already after 2 weeks, without affecting general cell health. To validate our model, activity of two autophagy inducers was tested. Both rapamycin and trehalose significantly reduced TAU aggregation levels suggesting that iPSC-derived neurons allow for the generation of a biologically relevant human Tauopathy model, highly suitable to screen for compounds that modulate TAU aggregation.http://europepmc.org/articles/PMC4697850?pdf=render |
| spellingShingle | An Verheyen Annick Diels Joyce Dijkmans Tutu Oyelami Giulia Meneghello Liesbeth Mertens Sofie Versweyveld Marianne Borgers Arjan Buist Pieter Peeters Miroslav Cik Using Human iPSC-Derived Neurons to Model TAU Aggregation. PLoS ONE |
| title | Using Human iPSC-Derived Neurons to Model TAU Aggregation. |
| title_full | Using Human iPSC-Derived Neurons to Model TAU Aggregation. |
| title_fullStr | Using Human iPSC-Derived Neurons to Model TAU Aggregation. |
| title_full_unstemmed | Using Human iPSC-Derived Neurons to Model TAU Aggregation. |
| title_short | Using Human iPSC-Derived Neurons to Model TAU Aggregation. |
| title_sort | using human ipsc derived neurons to model tau aggregation |
| url | http://europepmc.org/articles/PMC4697850?pdf=render |
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