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Alpha-Synuclein Inclusion Formation in Human Oligodendrocytes

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...

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Autores principales: Yoon, Ye-Seul, Ahn, Woo Jung, Ricarte, Diadem, Ortiz, Darlene, Shin, Chan Young, Lee, Seung-Jae, Lee, He-Jin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Society of Applied Pharmacology 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771843/
https://www.ncbi.nlm.nih.gov/pubmed/32536617
http://dx.doi.org/10.4062/biomolther.2020.081
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author Yoon, Ye-Seul
Ahn, Woo Jung
Ricarte, Diadem
Ortiz, Darlene
Shin, Chan Young
Lee, Seung-Jae
Lee, He-Jin
author_facet Yoon, Ye-Seul
Ahn, Woo Jung
Ricarte, Diadem
Ortiz, Darlene
Shin, Chan Young
Lee, Seung-Jae
Lee, He-Jin
author_sort Yoon, Ye-Seul
collection PubMed
description 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 neuron-derived 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 unidentified stem cell-like cells were present as well. When these cells were exposed to α-synuclein proteins secreted from neuron-like human neuroblastoma cells, oligodendrocytes developed perinuclear inclusion bodies with α-synuclein immunoreactivity, resembling GCIs, while the stem cell-like cells showed α-synuclein-positive, scattered puncta in the cytoplasm. In conclusion, we have established a human oligodendrocyte model for the study of GCI formation, and the characterization and use of this model might pave the way for understanding the pathogenesis of MSA.
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spelling pubmed-77718432021-01-01 Alpha-Synuclein Inclusion Formation in Human Oligodendrocytes Yoon, Ye-Seul Ahn, Woo Jung Ricarte, Diadem Ortiz, Darlene Shin, Chan Young Lee, Seung-Jae Lee, He-Jin Biomol Ther (Seoul) Original Article 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 neuron-derived 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 unidentified stem cell-like cells were present as well. When these cells were exposed to α-synuclein proteins secreted from neuron-like human neuroblastoma cells, oligodendrocytes developed perinuclear inclusion bodies with α-synuclein immunoreactivity, resembling GCIs, while the stem cell-like cells showed α-synuclein-positive, scattered puncta in the cytoplasm. In conclusion, we have established a human oligodendrocyte model for the study of GCI formation, and the characterization and use of this model might pave the way for understanding the pathogenesis of MSA. The Korean Society of Applied Pharmacology 2021-01-01 2020-06-15 /pmc/articles/PMC7771843/ /pubmed/32536617 http://dx.doi.org/10.4062/biomolther.2020.081 Text en Copyright © 2021, The Korean Society of Applied Pharmacology This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Yoon, Ye-Seul
Ahn, Woo Jung
Ricarte, Diadem
Ortiz, Darlene
Shin, Chan Young
Lee, Seung-Jae
Lee, He-Jin
Alpha-Synuclein Inclusion Formation in Human Oligodendrocytes
title Alpha-Synuclein Inclusion Formation in Human Oligodendrocytes
title_full Alpha-Synuclein Inclusion Formation in Human Oligodendrocytes
title_fullStr Alpha-Synuclein Inclusion Formation in Human Oligodendrocytes
title_full_unstemmed Alpha-Synuclein Inclusion Formation in Human Oligodendrocytes
title_short Alpha-Synuclein Inclusion Formation in Human Oligodendrocytes
title_sort alpha-synuclein inclusion formation in human oligodendrocytes
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771843/
https://www.ncbi.nlm.nih.gov/pubmed/32536617
http://dx.doi.org/10.4062/biomolther.2020.081
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