Molecular features underlying neurodegeneration identified through in vitro modeling of genetically diverse parkinson’s disease patients

The fact that Parkinson’s disease (PD) can arise from numerous genetic mutations suggests a unifying molecular pathology underlying the various genetic backgrounds. To address this hypothesis, we took an integrated approach utilizing in vitro disease modeling and comprehensive transcriptome profilin...

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Main Authors: Lin, Lin, Göke, Jonathan, Cukuroglu, Engin, Dranias, Mark R., VanDongen, Antonius M.J., Stanton, Lawrence W.
Other Authors: School of Biological Sciences
Format: Article
Language:English
Published: 2018
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Online Access:https://hdl.handle.net/10356/89993
http://hdl.handle.net/10220/46469
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-899932023-02-28T17:02:58Z Molecular features underlying neurodegeneration identified through in vitro modeling of genetically diverse parkinson’s disease patients Lin, Lin Göke, Jonathan Cukuroglu, Engin Dranias, Mark R. VanDongen, Antonius M.J. Stanton, Lawrence W. School of Biological Sciences DRNTU::Science::Biological sciences Alternative RNA Splicing Article The fact that Parkinson’s disease (PD) can arise from numerous genetic mutations suggests a unifying molecular pathology underlying the various genetic backgrounds. To address this hypothesis, we took an integrated approach utilizing in vitro disease modeling and comprehensive transcriptome profiling to advance our understanding of PD progression and the concordant downstream signaling pathways across divergent genetic predispositions. To model PD in vitro, we generated neurons harboring disease-causing mutations from patient-specific, induced pluripotent stem cells (iPSCs). We observed signs of degeneration in midbrain dopaminergic neurons, reflecting the cardinal feature of PD. Gene expression signatures of PD neurons provided molecular insights into disease phenotypes observed in vitro, including oxidative stress vulnerability and altered neuronal activity. Notably, PD neurons show that elevated RBFOX1, a gene previously linked to neurodevelopmental diseases, underlies a pattern of alternative RNA-processing associated with PD-specific phenotypes. Published version 2018-10-29T08:54:48Z 2019-12-06T17:38:14Z 2018-10-29T08:54:48Z 2019-12-06T17:38:14Z 2016 Journal Article Lin, L., Göke, J., Cukuroglu, E., Dranias, M., VanDongen, A., & Stanton, L. (2016). Molecular Features Underlying Neurodegeneration Identified through In Vitro Modeling of Genetically Diverse Parkinson’s Disease Patients. Cell Reports, 15(11), 2411-2426. doi:10.1016/j.celrep.2016.05.022 2211-1247 https://hdl.handle.net/10356/89993 http://hdl.handle.net/10220/46469 10.1016/j.celrep.2016.05.022 en Cell Reports © 2016 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). 46 p. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic DRNTU::Science::Biological sciences
Alternative RNA Splicing
Article
spellingShingle DRNTU::Science::Biological sciences
Alternative RNA Splicing
Article
Lin, Lin
Göke, Jonathan
Cukuroglu, Engin
Dranias, Mark R.
VanDongen, Antonius M.J.
Stanton, Lawrence W.
Molecular features underlying neurodegeneration identified through in vitro modeling of genetically diverse parkinson’s disease patients
description The fact that Parkinson’s disease (PD) can arise from numerous genetic mutations suggests a unifying molecular pathology underlying the various genetic backgrounds. To address this hypothesis, we took an integrated approach utilizing in vitro disease modeling and comprehensive transcriptome profiling to advance our understanding of PD progression and the concordant downstream signaling pathways across divergent genetic predispositions. To model PD in vitro, we generated neurons harboring disease-causing mutations from patient-specific, induced pluripotent stem cells (iPSCs). We observed signs of degeneration in midbrain dopaminergic neurons, reflecting the cardinal feature of PD. Gene expression signatures of PD neurons provided molecular insights into disease phenotypes observed in vitro, including oxidative stress vulnerability and altered neuronal activity. Notably, PD neurons show that elevated RBFOX1, a gene previously linked to neurodevelopmental diseases, underlies a pattern of alternative RNA-processing associated with PD-specific phenotypes.
author2 School of Biological Sciences
author_facet School of Biological Sciences
Lin, Lin
Göke, Jonathan
Cukuroglu, Engin
Dranias, Mark R.
VanDongen, Antonius M.J.
Stanton, Lawrence W.
format Article
author Lin, Lin
Göke, Jonathan
Cukuroglu, Engin
Dranias, Mark R.
VanDongen, Antonius M.J.
Stanton, Lawrence W.
author_sort Lin, Lin
title Molecular features underlying neurodegeneration identified through in vitro modeling of genetically diverse parkinson’s disease patients
title_short Molecular features underlying neurodegeneration identified through in vitro modeling of genetically diverse parkinson’s disease patients
title_full Molecular features underlying neurodegeneration identified through in vitro modeling of genetically diverse parkinson’s disease patients
title_fullStr Molecular features underlying neurodegeneration identified through in vitro modeling of genetically diverse parkinson’s disease patients
title_full_unstemmed Molecular features underlying neurodegeneration identified through in vitro modeling of genetically diverse parkinson’s disease patients
title_sort molecular features underlying neurodegeneration identified through in vitro modeling of genetically diverse parkinson’s disease patients
publishDate 2018
url https://hdl.handle.net/10356/89993
http://hdl.handle.net/10220/46469
_version_ 1759858311380860928