Cited by 686Parkinson's Disease Mechanisms and TreatmentsNeuroinflammation and Neurodegeneration MechanismsNuclear Receptors and Signaling

Glial cytoplasmic inclusions in white matter oligodendrocytes of multiple system atrophy brains contain insoluble α‐synuclein

Tu, Pang‐hsien, Galvin, James E., Baba, Minami, Giasson, Benoit, Tomita, Taisuke, Leight, Susan, Nakajo, Shigeo, Iwatsubo, Takeshi +2 more·1998·Annals of Neurology

Abstract

Recently, α‐synuclein was shown to be a structural component of the filaments in Lewy bodies (LBs) of Parkinson's disease (PD), dementia with LBs (DLB) as well as the LB variant of Alzheimer's disease, and this suggests that α‐synuclein could play a mechanistic role in the pathogenesis of these disorders. To determine whether α‐synuclein is a building block of inclusions in other neurodegenerative movement disorders, we examined brains from patients with multiple system atrophy (MSA) and detected α‐synuclein, but not β‐ or γ‐synuclein, in glial cytoplasmic inclusions (GCIs) throughout the MSA brain. In MSA white matter, α‐synuclein–positive GCIs were restricted to oligodendrocytes, and α‐synuclein accumulated selectively in MSA white matter with α‐synuclein–positive GCIs. Taken together with evidence that LBs contain insoluble α‐synuclein, our data suggest that a reduction in the solubility of α‐synuclein may induce this protein to form filaments that aggregate into cytoplasmic inclusions, which contribute to the dysfunction or death of glial cells as well as neurons in neurodegenerative disorders with different phenotypes.

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Crossref · 10.1002/ana.410440324

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Authors
Tu, P., Galvin, J. E., Baba, M., Giasson, B., Tomita, T., Leight, S., Nakajo, S., Iwatsubo, T., Trojanowski, J. Q., & Lee, V. M. ‐.
Affiliations
  • University of Pennsylvania (US)
  • The University of Tokyo (JP)
  • SHOWA Medical University (JP)
Corresponding author
Lee, Virginia M.‐Y.
Venue
Annals of Neurology
Publisher
Wiley
Published
1998-09
Volume
44
Issue
3
Pages
415-422
ISSN
  • 0364-5134 (ISSN-L)
  • 1531-8249
OpenAlex
W2133068803
Cited by
686
References
43
Citations by year
2026: 14 · 2025: 21 · 2024: 33 · 2023: 23 · 2022: 25 · 2021: 28 · 2020: 21 · 2019: 24 · 2018: 21 · 2017: 23 · 2016: 12 · 2015: 20 · 2014: 24 · 2013: 18 · 2012: 17
FWCI
30.21
Type
journal article
Language
en
Open access
closed
Locations
  • Annals of Neurology (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Mental Health (MH.NS 31862)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
Keywords
alpha-synuclein, glial cytoplasmic inclusions, multiple system atrophy, oligodendrocytes, white matter, Lewy bodies, protein aggregation, neurodegenerative movement disorders, immunoelectron microscopy, synuclein
MeSH terms
Adult, Aged, Aged, 80 and over, Antibodies, Inclusion Bodies, Female, Humans, Male, Actin Cytoskeleton, Middle Aged, Myelin Sheath, Nerve Tissue Proteins, Neuroglia, Oligodendroglia, Solubility, Multiple System Atrophy, Synucleins, alpha-Synuclein, gamma-Synuclein

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