α‐Synuclein Pathology Spreads in a Midbrain–Hindbrain Assembloid Model
Abstract Understanding the progression of α‐synuclein pathology in neurodegenerative diseases such as Parkinson's disease (PD) is a longstanding challenge. Here, a novel midbrain–hindbrain‐assembloid model that recapitulates the spread of α‐synuclein pathology observed in PD patients, akin to B...
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| Format: | Article |
| Language: | English |
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Wiley
2025-05-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202409040 |
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| author | Gemma Gomez‐Giro Daniela Frangenberg Daniela Vega Alise Zagare Kyriaki Barmpa Paul M. A. Antony Graham Robertson Rahman Sabahi‐Kaviani Kristian Haendler Nathalie Kruse Florentia Papastefanaki Rebecca Matsas Malte Spielmann Regina Luttge Jens C. Schwamborn |
| author_facet | Gemma Gomez‐Giro Daniela Frangenberg Daniela Vega Alise Zagare Kyriaki Barmpa Paul M. A. Antony Graham Robertson Rahman Sabahi‐Kaviani Kristian Haendler Nathalie Kruse Florentia Papastefanaki Rebecca Matsas Malte Spielmann Regina Luttge Jens C. Schwamborn |
| author_sort | Gemma Gomez‐Giro |
| collection | DOAJ |
| description | Abstract Understanding the progression of α‐synuclein pathology in neurodegenerative diseases such as Parkinson's disease (PD) is a longstanding challenge. Here, a novel midbrain–hindbrain‐assembloid model that recapitulates the spread of α‐synuclein pathology observed in PD patients, akin to Braak's hypothesis, is presented. Initially, the presence α‐synuclein pathology is demonstrated in the hindbrain organoids. Subsequently, sophisticated tissue engineering methods are employed to create midbrain–hindbrain assembloids. These assembloids allow investigation and description of the spreading of α‐synuclein pathology, as it progresses from the hindbrain components to the midbrain regions within the integrated structure. It is observed that an increase in α‐synuclein in the hindbrain can induce transfer of the pathology into the healthy midbrain, as well as cause changes at the synapse level. The presented model constitutes a robust in vitro platform for investigating the mechanisms underlying α‐synuclein spreading and disease progression, and holding potential for the screening of prospective therapeutics targeting the pathological propagation in PD and related synucleinopathies. |
| format | Article |
| id | doaj-art-ff038201aa6d49a2a01f2cf86e2b3f43 |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-ff038201aa6d49a2a01f2cf86e2b3f432025-08-20T02:34:43ZengWileyAdvanced Science2198-38442025-05-011220n/an/a10.1002/advs.202409040α‐Synuclein Pathology Spreads in a Midbrain–Hindbrain Assembloid ModelGemma Gomez‐Giro0Daniela Frangenberg1Daniela Vega2Alise Zagare3Kyriaki Barmpa4Paul M. A. Antony5Graham Robertson6Rahman Sabahi‐Kaviani7Kristian Haendler8Nathalie Kruse9Florentia Papastefanaki10Rebecca Matsas11Malte Spielmann12Regina Luttge13Jens C. Schwamborn14Developmental and Cellular Biology Luxembourg Centre for Systems Biomedicine University of Luxembourg Belvaux L‐4367 LuxembourgDevelopmental and Cellular Biology Luxembourg Centre for Systems Biomedicine University of Luxembourg Belvaux L‐4367 LuxembourgDevelopmental and Cellular Biology Luxembourg Centre for Systems Biomedicine University of Luxembourg Belvaux L‐4367 LuxembourgDevelopmental and Cellular Biology Luxembourg Centre for Systems Biomedicine University of Luxembourg Belvaux L‐4367 LuxembourgDevelopmental and Cellular Biology Luxembourg Centre for Systems Biomedicine University of Luxembourg Belvaux L‐4367 LuxembourgBioimaging Platform Luxembourg Centre for Systems Biomedicine University of Luxembourg Belvaux L‐4367 LuxembourgDevelopmental and Cellular Biology Luxembourg Centre for Systems Biomedicine University of Luxembourg Belvaux L‐4367 LuxembourgDepartment of Mechanical Engineering Eindhoven University of Technology (TUE) Eindhoven 5612 AE The NetherlandsInstitute of Human Genetics Universitätsklinikum Schleswig–Holstein (UKSH) 23538 Lübeck GermanyInstitute of Human Genetics Universitätsklinikum Schleswig–Holstein (UKSH) 23538 Lübeck GermanyHuman Embryonic and Induced Pluripotent Stem Cell Unit Hellenic Pasteur Institute Athens 11521 GreeceHuman Embryonic and Induced Pluripotent Stem Cell Unit Hellenic Pasteur Institute Athens 11521 GreeceInstitute of Human Genetics Universitätsklinikum Schleswig–Holstein (UKSH) 23538 Lübeck GermanyDepartment of Mechanical Engineering Eindhoven University of Technology (TUE) Eindhoven 5612 AE The NetherlandsDevelopmental and Cellular Biology Luxembourg Centre for Systems Biomedicine University of Luxembourg Belvaux L‐4367 LuxembourgAbstract Understanding the progression of α‐synuclein pathology in neurodegenerative diseases such as Parkinson's disease (PD) is a longstanding challenge. Here, a novel midbrain–hindbrain‐assembloid model that recapitulates the spread of α‐synuclein pathology observed in PD patients, akin to Braak's hypothesis, is presented. Initially, the presence α‐synuclein pathology is demonstrated in the hindbrain organoids. Subsequently, sophisticated tissue engineering methods are employed to create midbrain–hindbrain assembloids. These assembloids allow investigation and description of the spreading of α‐synuclein pathology, as it progresses from the hindbrain components to the midbrain regions within the integrated structure. It is observed that an increase in α‐synuclein in the hindbrain can induce transfer of the pathology into the healthy midbrain, as well as cause changes at the synapse level. The presented model constitutes a robust in vitro platform for investigating the mechanisms underlying α‐synuclein spreading and disease progression, and holding potential for the screening of prospective therapeutics targeting the pathological propagation in PD and related synucleinopathies.https://doi.org/10.1002/advs.202409040α‐synucleinbrain organoidin vitro disease modelingParkinson's disease |
| spellingShingle | Gemma Gomez‐Giro Daniela Frangenberg Daniela Vega Alise Zagare Kyriaki Barmpa Paul M. A. Antony Graham Robertson Rahman Sabahi‐Kaviani Kristian Haendler Nathalie Kruse Florentia Papastefanaki Rebecca Matsas Malte Spielmann Regina Luttge Jens C. Schwamborn α‐Synuclein Pathology Spreads in a Midbrain–Hindbrain Assembloid Model Advanced Science α‐synuclein brain organoid in vitro disease modeling Parkinson's disease |
| title | α‐Synuclein Pathology Spreads in a Midbrain–Hindbrain Assembloid Model |
| title_full | α‐Synuclein Pathology Spreads in a Midbrain–Hindbrain Assembloid Model |
| title_fullStr | α‐Synuclein Pathology Spreads in a Midbrain–Hindbrain Assembloid Model |
| title_full_unstemmed | α‐Synuclein Pathology Spreads in a Midbrain–Hindbrain Assembloid Model |
| title_short | α‐Synuclein Pathology Spreads in a Midbrain–Hindbrain Assembloid Model |
| title_sort | α synuclein pathology spreads in a midbrain hindbrain assembloid model |
| topic | α‐synuclein brain organoid in vitro disease modeling Parkinson's disease |
| url | https://doi.org/10.1002/advs.202409040 |
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