Modeling early phenotypes of Parkinson’s disease by age-induced midbrain-striatum assembloids

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 EdenhoferJens C. Schwamborn (Corresponding author)

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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.

Original languageEnglish
Article number1561
Number of pages19
JournalCommunications biology
Volume7
Issue number1
DOIs
Publication statusPublished - 23 Nov 2024

Bibliographical note

Publisher Copyright:
© The Author(s) 2024.

Keywords

  • Parkinson Disease/pathology
  • Mesencephalon/metabolism
  • Humans
  • Phenotype
  • Aging/pathology
  • Corpus Striatum/metabolism
  • Dopaminergic Neurons/metabolism
  • Animals
  • Substantia Nigra/metabolism

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