Lewy Body-like Pathology and Loss of Dopaminergic Neurons in Midbrain Organoids Derived from Familial Parkinson's Disease Patient

Authors

Andrea Becerra-Calixto
Abhisek Mukherjee
Santiago Ramirez
Sofia Sepulveda
Tirthankar Sinha
Rabab Al-Lahham
Nicole De Gregorio
Camila Gherardelli
Claudio Soto

Publication Date

2-15-2023

Journal

Cells

Abstract

Progressive accumulation of α-Synuclein (αSyn) in Lewy bodies (LBs) and loss of dopaminergic (DA) neurons are the hallmark pathological features of Parkinson's disease (PD). Although currently available in vitro and in vivo models have provided crucial information about PD pathogenesis, the mechanistic link between the progressive accumulation of αSyn into LBs and the loss of DA neurons is still unclear. To address this, it is critical to model LB formation and DA neuron loss, the two key neuropathological aspects of PD, in a relevant in vitro system. In this study, we developed a human midbrain-like organoid (hMBO) model of PD. We demonstrated that hMBOs generated from induced pluripotent stem cells (hiPSCs), derived from a familial PD (fPD) patient carrying αSyn gene (

Keywords

human midbrain-like organoids, Parkinson’s disease, 3D models, Lewy body disease