Modeling Parkinson’s disease pathology in human dopaminergic neurons by sequential exposure to α-synuclein fibrils and proinflammatory cytokines

Authors: Armin Bayati, Riham Ayoubi, Adriana Aguila, Cornelia E. Zorca, Ghislaine Deyab, Chanshuai Han, Sherilyn Junelle Recinto, Emmanuelle Nguyen-Renou, Cecilia Rocha, Gilles Maussion, Wen Luo, Irina Shlaifer, Emily Banks, Ian McDowell, Esther Del Cid Pellitero, Xue Er Ding, Behrang Sharif, Philippe Séguéla, Moein Yaqubi, Carol X.-Q. Chen, Zhipeng You, Narges Abdian, Heidi M. McBride, Edward A. Fon, Jo Anne Stratton, Thomas M. Durcan, Patrick C. Nahirney and Peter S. McPherson

Nature Neuroscience, 08 October 2024

Scientists use Axion’s Maestro Edge MEA system to explore the role of the immune system in neurodegenerative disease.

Lewy bodies (LBs) are a hallmark pathological feature of Parkinson's disease (PD) but the mechanisms underlying their formation remain poorly understood, in part due to a lack of biologically relevant in vitro models. With emerging evidence suggesting that the immune system plays a role in PD onset and progression, researchers in this study used iPSC-derived dopaminergic neurons and immune challenge to assess the impact of the immune system in LB formation. To characterize the iPSC-derived cortical and dopaminergic neurons in vitro with no labels or dyes, the team used Axion BioSystems' hands-free Maestro microelectrode array (MEA) platform. Ultimately, the findings showed that dopaminergic neurons formed LB-like inclusions after challenge with interferon-gamma or interleukin-1 beta or when co-cultured with activated microglia, but not without immune challenge, suggesting a key immune role in LB formation. Overall, the authors conclude that the method “provides a reproducible and unlimited source of LB-like inclusions,” that may enable scientists to “map the entire sequence of events in neurodegenerative disorders,” and pave the way to new discoveries.