Modeling early phenotypes of Parkinson’s disease by age-induced midbrain-striatum assembloids
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.
Authors
- Frank Edenhofer (ORCID: https://orcid.org/0000-0002-6489-714X)
- Alessandro Bellapianta (ORCID: https://orcid.org/0000-0002-3375-9940)
- Elisa Gabassi (ORCID: https://orcid.org/0000-0001-6053-503X)
- Cláudia Saraiva (ORCID: https://orcid.org/0000-0003-4866-8790)
- Graham Robertson (ORCID: https://orcid.org/0000-0002-3841-874X)
- Sarah Spitz (ORCID: https://orcid.org/0000-0001-7980-7955)
- Juan Eduardo Rodriguez-Gatica (ORCID: https://orcid.org/0000-0003-4123-0104)
- Ulrich Kubitscheck (ORCID: https://orcid.org/0000-0003-3750-5355)
- Diego Lopez‐Pigozzi (ORCID: https://orcid.org/0000-0002-6178-5951)
- Kyriaki Barmpa (ORCID: https://orcid.org/0000-0003-3938-4745)
- Regina Lüttge (ORCID: https://orcid.org/0000-0002-8486-5866)
- Peter Ertl (ORCID: https://orcid.org/0000-0002-7625-2445)
- Rebecca Matsas (ORCID: https://orcid.org/0000-0002-4027-348X)
- Rahman Sabahi‐Kaviani (ORCID: https://orcid.org/0000-0003-3534-7218)
- Jens C. Schwamborn (ORCID: https://orcid.org/0000-0003-4496-0559)
- Mario Bortolozzi (ORCID: https://orcid.org/0000-0001-7198-9838)
- Gemma Gomez‐Giro (ORCID: https://orcid.org/0000-0002-7259-5002)
- Florentia Papastefanaki (ORCID: https://orcid.org/0000-0003-1237-642X)
- Paul Antony (ORCID: https://orcid.org/0000-0002-0450-9301)
- Ahmad Salti (ORCID: https://orcid.org/0000-0002-7678-0125)
- Konstanze Brandauer (ORCID: https://orcid.org/0009-0006-4852-6142)
Institutions
- Johannes Kepler University of Linz (AT)
- University of Bonn (DE)
- University of Padua (IT)
- Innsbruck Medical University (AT)
- TU Wien (AT)
- University of Luxembourg (LU)
- Universität Innsbruck (AT)
- Veneto Institute of Molecular Medicine (IT)
- Kepler Universitätsklinikum (AT)
- Pasteur Hellenic Institute (GR)
- Eindhoven University of Technology (NL)
Publication Details
- Journal
- Communications Biology
- Published
- 2024-11-23
- DOI
- https://doi.org/10.1038/s42003-024-07273-4
- Citations
- 17
- Primary Topic
- Parkinson's Disease Mechanisms and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 6.28
Funders
- European Commission
- Deutsche Forschungsgemeinschaft
- Fonds National de la Recherche Luxembourg
- Austrian Science Fund
- Hellenic Foundation for Research and Innovation
- Horizon 2020 Framework Programme