Modeling early phenotypes of Parkinson’s disease by age-induced midbrain-striatum assembloids
Abstract Parkinson’s disease, an aging-associated neurodegenerative disorder, is characterised by nigrostriatal pathway dysfunction caused by the gradual loss of dopaminergic neurons in the substantia nigra pars compacta of the midbrain. Human in vitro models are enabling the study of the dopaminerg...
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Nature Portfolio
2024-11-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-024-07273-4 |
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| author | Kyriaki Barmpa Claudia Saraiva Diego Lopez-Pigozzi Gemma Gomez-Giro Elisa Gabassi Sarah Spitz Konstanze Brandauer Juan E. Rodriguez Gatica Paul Antony Graham Robertson Rahman Sabahi-Kaviani Alessandro Bellapianta Florentia Papastefanaki Regina Luttge Ulrich Kubitscheck Ahmad Salti Peter Ertl Mario Bortolozzi Rebecca Matsas Frank Edenhofer Jens C. Schwamborn |
| author_facet | Kyriaki Barmpa Claudia Saraiva Diego Lopez-Pigozzi Gemma Gomez-Giro Elisa Gabassi Sarah Spitz Konstanze Brandauer Juan E. Rodriguez Gatica Paul Antony Graham Robertson Rahman Sabahi-Kaviani Alessandro Bellapianta Florentia Papastefanaki Regina Luttge Ulrich Kubitscheck Ahmad Salti Peter Ertl Mario Bortolozzi Rebecca Matsas Frank Edenhofer Jens C. Schwamborn |
| author_sort | Kyriaki Barmpa |
| collection | DOAJ |
| description | Abstract Parkinson’s disease, an aging-associated neurodegenerative disorder, is characterised by nigrostriatal pathway dysfunction caused by the gradual loss of dopaminergic neurons in the substantia nigra pars compacta of the midbrain. Human in vitro models are enabling the study of the dopaminergic neurons’ loss, but not the dysregulation within the dopaminergic network in the nigrostriatal pathway. Additionally, these models do not incorporate aging characteristics which potentially contribute to the development of Parkinson’s disease. Here we present a nigrostriatal pathway model based on midbrain-striatum assembloids with inducible aging. We show that these assembloids can develop characteristics of the nigrostriatal connectivity, with catecholamine release from the midbrain to the striatum and synapse formation between midbrain and striatal neurons. Moreover, Progerin-overexpressing assembloids acquire aging traits that lead to early neurodegenerative phenotypes. This model shall help to reveal the contribution of aging as well as nigrostriatal connectivity to the onset and progression of Parkinson’s disease. |
| format | Article |
| id | doaj-art-01a3e63dcff24b67a4571fd2ecb5411b |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-01a3e63dcff24b67a4571fd2ecb5411b2024-11-24T12:39:07ZengNature PortfolioCommunications Biology2399-36422024-11-017111910.1038/s42003-024-07273-4Modeling early phenotypes of Parkinson’s disease by age-induced midbrain-striatum assembloidsKyriaki Barmpa0Claudia Saraiva1Diego Lopez-Pigozzi2Gemma Gomez-Giro3Elisa Gabassi4Sarah Spitz5Konstanze Brandauer6Juan E. Rodriguez Gatica7Paul Antony8Graham Robertson9Rahman Sabahi-Kaviani10Alessandro Bellapianta11Florentia Papastefanaki12Regina Luttge13Ulrich Kubitscheck14Ahmad Salti15Peter Ertl16Mario Bortolozzi17Rebecca Matsas18Frank Edenhofer19Jens C. Schwamborn20Developmental and Cellular Biology, Luxembourg Centre for Systems Biomedicine, University of LuxembourgDevelopmental and Cellular Biology, Luxembourg Centre for Systems Biomedicine, University of LuxembourgDepartment of Physics and Astronomy “G. Galilei”, University of PaduaDevelopmental and Cellular Biology, Luxembourg Centre for Systems Biomedicine, University of LuxembourgGenomics, Stem Cell & Regenerative Medicine Group and CMBI, Institute of Molecular Biology, University of InnsbruckInstitute of Applied Synthetic Chemistry, Vienna University of TechnologyInstitute of Applied Synthetic Chemistry, Vienna University of TechnologyClausius Institute of Physical and Theoretical Chemistry, University of BonnDevelopmental and Cellular Biology, Luxembourg Centre for Systems Biomedicine, University of LuxembourgDevelopmental and Cellular Biology, Luxembourg Centre for Systems Biomedicine, University of LuxembourgEindhoven University of Technology, MicrosystemsJohannes Kepler University Linz, Kepler University Hospital, University Clinic for Ophthalmology and OptometryLaboratory of Cellular and Molecular Neurobiology-Stem Cells, Hellenic Pasteur InstituteEindhoven University of Technology, MicrosystemsClausius Institute of Physical and Theoretical Chemistry, University of BonnGenomics, Stem Cell & Regenerative Medicine Group and CMBI, Institute of Molecular Biology, University of InnsbruckInstitute of Applied Synthetic Chemistry, Vienna University of TechnologyDepartment of Physics and Astronomy “G. Galilei”, University of PaduaLaboratory of Cellular and Molecular Neurobiology-Stem Cells, Hellenic Pasteur InstituteGenomics, Stem Cell & Regenerative Medicine Group and CMBI, Institute of Molecular Biology, University of InnsbruckDevelopmental and Cellular Biology, Luxembourg Centre for Systems Biomedicine, University of LuxembourgAbstract Parkinson’s disease, an aging-associated neurodegenerative disorder, is characterised by nigrostriatal pathway dysfunction caused by the gradual loss of dopaminergic neurons in the substantia nigra pars compacta of the midbrain. Human in vitro models are enabling the study of the dopaminergic neurons’ loss, but not the dysregulation within the dopaminergic network in the nigrostriatal pathway. Additionally, these models do not incorporate aging characteristics which potentially contribute to the development of Parkinson’s disease. Here we present a nigrostriatal pathway model based on midbrain-striatum assembloids with inducible aging. We show that these assembloids can develop characteristics of the nigrostriatal connectivity, with catecholamine release from the midbrain to the striatum and synapse formation between midbrain and striatal neurons. Moreover, Progerin-overexpressing assembloids acquire aging traits that lead to early neurodegenerative phenotypes. This model shall help to reveal the contribution of aging as well as nigrostriatal connectivity to the onset and progression of Parkinson’s disease.https://doi.org/10.1038/s42003-024-07273-4 |
| spellingShingle | Kyriaki Barmpa Claudia Saraiva Diego Lopez-Pigozzi Gemma Gomez-Giro Elisa Gabassi Sarah Spitz Konstanze Brandauer Juan E. Rodriguez Gatica Paul Antony Graham Robertson Rahman Sabahi-Kaviani Alessandro Bellapianta Florentia Papastefanaki Regina Luttge Ulrich Kubitscheck Ahmad Salti Peter Ertl Mario Bortolozzi Rebecca Matsas Frank Edenhofer Jens C. Schwamborn Modeling early phenotypes of Parkinson’s disease by age-induced midbrain-striatum assembloids Communications Biology |
| title | Modeling early phenotypes of Parkinson’s disease by age-induced midbrain-striatum assembloids |
| title_full | Modeling early phenotypes of Parkinson’s disease by age-induced midbrain-striatum assembloids |
| title_fullStr | Modeling early phenotypes of Parkinson’s disease by age-induced midbrain-striatum assembloids |
| title_full_unstemmed | Modeling early phenotypes of Parkinson’s disease by age-induced midbrain-striatum assembloids |
| title_short | Modeling early phenotypes of Parkinson’s disease by age-induced midbrain-striatum assembloids |
| title_sort | modeling early phenotypes of parkinson s disease by age induced midbrain striatum assembloids |
| url | https://doi.org/10.1038/s42003-024-07273-4 |
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