Aggregated alpha-synuclein (α-Syn) in neurons is a hallmark of Parkinson’s disease (PD) and other synucleinopathies. Recent advances (1) in the production and purification of synthetic assemblies of α-Syn, (2) in the design and production of microfluidic devices allowing the construction of oriented and compartmentalized neuronal network on a chip, and (3) in the differentiation of human pluripotent stem cells (hPSCs) into specific neuronal subtypes now allow the study of cellular and molecular determinants of the prion-like properties of α-Syn in vitro. Here, we described the methods we used to reconstruct a cortico-cortical human neuronal network in microfluidic devices and how to take advantage of this cellular model to characterize (1) the prion-like properties of different α-Syn strains and (2) the neuronal dysfunctions and the alterations associated with the exposure to α-Syn strains or the nucleation of endogenous α-Syn protein in vitro.
CITATION STYLE
Gribaudo, S., Bousset, L., Courte, J., Melki, R., Peyrin, J. M., & Perrier, A. L. (2023). Propagation of Distinct α-Synuclein Strains Within Human Reconstructed Neuronal Network and Associated Neuronal Dysfunctions. In Methods in Molecular Biology (Vol. 2551, pp. 357–378). Humana Press Inc. https://doi.org/10.1007/978-1-0716-2597-2_24
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