Alpha-Synuclein Inclusion Formation in Human Oligodendrocytes

Biomolecules & Therapeutics
Ye-Seul YoonHe-Jin Lee

Abstract

Multiple system atrophy (MSA) is a neurodegenerative disease characterized by presence of α-synuclein-positive inclusions in the cytoplasm of oligodendrocytes. These glial cytoplasmic inclusions (GCIs) are considered an integral part of the pathogenesis of MSA, leading to demyelination and neuronal demise. What is most puzzling in the research fields of GCIs is the origin of α-synuclein aggregates in GCIs, since adult oligodendrocytes do not express high levels of α-synuclein. The most recent leading hypothesis is that GCIs form via transfer and accumulation of α-synuclein from neurons to oligodendrocytes. However, studies regarding this subject are limited due to the absence of proper human cell models, to demonstrate the entry and accumulation of neuronal α-synuclein in human oligodendrocytes. Here, we generated mature human oligodendrocytes that can take up neuronderived α-synuclein and form GCI-like inclusions. Mature human oligodendrocytes are derived from neural stem cells via "oligosphere" formation and then into oligodendrocytes, treating the cells with the proper differentiation factors at each step. In the final cell preparations, oligodendrocytes consist of the majority population, while some astrocytes and unidentif...Continue Reading

References

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Nov 20, 2019·Experimental & Molecular Medicine·He-Jin LeeSeung-Jae Lee

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Citations

Dec 3, 2020·Frontiers in Cell and Developmental Biology·Yu-Mi JeonHyung-Jun Kim
Jun 3, 2021·International Journal of Molecular Sciences·Panagiota Mavroeidi, Maria Xilouri
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Rita Rosado-RamosCláudia Nunes Dos Santos

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