TY - JOUR
T1 - Modeling early phenotypes of Parkinson’s disease by age-induced midbrain-striatum assembloids
AU - Barmpa, Kyriaki
AU - Saraiva, Claudia
AU - Lopez-Pigozzi, Diego
AU - Gomez-Giro, Gemma
AU - Gabassi, Elisa
AU - Spitz, Sarah
AU - Brandauer, Konstanze
AU - Rodriguez Gatica, Juan E.
AU - Antony, Paul
AU - Robertson, Graham
AU - Sabahi-Kaviani, Rahman
AU - Bellapianta, Alessandro
AU - Papastefanaki, Florentia
AU - Luttge, Regina
AU - Kubitscheck, Ulrich
AU - Salti, Ahmad
AU - Ertl, Peter
AU - Bortolozzi, Mario
AU - Matsas, Rebecca
AU - Edenhofer, Frank
AU - Schwamborn, Jens C.
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/11/23
Y1 - 2024/11/23
N2 - 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.
AB - 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.
KW - Parkinson Disease/pathology
KW - Mesencephalon/metabolism
KW - Humans
KW - Phenotype
KW - Aging/pathology
KW - Corpus Striatum/metabolism
KW - Dopaminergic Neurons/metabolism
KW - Animals
KW - Substantia Nigra/metabolism
UR - http://www.scopus.com/inward/record.url?scp=85209909342&partnerID=8YFLogxK
U2 - 10.1038/s42003-024-07273-4
DO - 10.1038/s42003-024-07273-4
M3 - Article
C2 - 39580573
AN - SCOPUS:85209909342
SN - 2399-3642
VL - 7
JO - Communications biology
JF - Communications biology
IS - 1
M1 - 1561
ER -
