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Glial cytoplasmic inclusions in white matter oligodendrocytes of multiple system atrophy brains contain insoluble alpha-synuclein.
Ann Neurol. 1998 Sep; 44(3):415-22.AN

Abstract

Recently, alpha-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 alpha-synuclein could play a mechanistic role in the pathogenesis of these disorders. To determine whether alpha-synuclein is a building block of inclusions in other neurodegenerative movement disorders, we examined brains from patients with multiple system atrophy (MSA) and detected alpha-synuclein, but not beta- or gamma-synuclein, in glial cytoplasmic inclusions (GCIs) throughout the MSA brain. In MSA white matter, alpha-synuclein-positive GCIs were restricted to oligodendrocytes, and alpha-synuclein was localized to the filaments in GCIs by immunoelectron microscopy. Finally, we demonstrated that insoluble alpha-synuclein accumulated selectively in MSA white matter with alpha-synuclein-positive GCIs. Taken together with evidence that LBs contain insoluble alpha-synuclein, our data suggest that a reduction in the solubility of alpha-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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Authors+Show Affiliations

Tu PH
Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, USA.
Galvin JE
No affiliation info available
Baba M
No affiliation info available
Giasson B
No affiliation info available
Tomita T
No affiliation info available
Leight S
No affiliation info available
Nakajo S
No affiliation info available
Iwatsubo T
No affiliation info available
Trojanowski JQ
No affiliation info available
Lee VM
No affiliation info available

MeSH

Actin CytoskeletonAdultAgedAged, 80 and overAntibodiesFemaleHumansInclusion BodiesMaleMiddle AgedMultiple System AtrophyMyelin SheathNerve Tissue ProteinsNeurogliaOligodendrogliaSolubilitySynucleinsalpha-Synucleingamma-Synuclein

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9749615

Citation

Tu, P H., et al. "Glial Cytoplasmic Inclusions in White Matter Oligodendrocytes of Multiple System Atrophy Brains Contain Insoluble Alpha-synuclein." Annals of Neurology, vol. 44, no. 3, 1998, pp. 415-22.
Tu PH, Galvin JE, Baba M, et al. Glial cytoplasmic inclusions in white matter oligodendrocytes of multiple system atrophy brains contain insoluble alpha-synuclein. Ann Neurol. 1998;44(3):415-22.
Tu, P. H., Galvin, J. E., Baba, M., Giasson, B., Tomita, T., Leight, S., Nakajo, S., Iwatsubo, T., Trojanowski, J. Q., & Lee, V. M. (1998). Glial cytoplasmic inclusions in white matter oligodendrocytes of multiple system atrophy brains contain insoluble alpha-synuclein. Annals of Neurology, 44(3), 415-22.
Tu PH, et al. Glial Cytoplasmic Inclusions in White Matter Oligodendrocytes of Multiple System Atrophy Brains Contain Insoluble Alpha-synuclein. Ann Neurol. 1998;44(3):415-22. PubMed PMID: 9749615.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Glial cytoplasmic inclusions in white matter oligodendrocytes of multiple system atrophy brains contain insoluble alpha-synuclein. AU - Tu,P H, AU - Galvin,J E, AU - Baba,M, AU - Giasson,B, AU - Tomita,T, AU - Leight,S, AU - Nakajo,S, AU - Iwatsubo,T, AU - Trojanowski,J Q, AU - Lee,V M, PY - 1998/9/28/pubmed PY - 1998/9/28/medline PY - 1998/9/28/entrez SP - 415 EP - 22 JF - Annals of neurology JO - Ann Neurol VL - 44 IS - 3 N2 - Recently, alpha-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 alpha-synuclein could play a mechanistic role in the pathogenesis of these disorders. To determine whether alpha-synuclein is a building block of inclusions in other neurodegenerative movement disorders, we examined brains from patients with multiple system atrophy (MSA) and detected alpha-synuclein, but not beta- or gamma-synuclein, in glial cytoplasmic inclusions (GCIs) throughout the MSA brain. In MSA white matter, alpha-synuclein-positive GCIs were restricted to oligodendrocytes, and alpha-synuclein was localized to the filaments in GCIs by immunoelectron microscopy. Finally, we demonstrated that insoluble alpha-synuclein accumulated selectively in MSA white matter with alpha-synuclein-positive GCIs. Taken together with evidence that LBs contain insoluble alpha-synuclein, our data suggest that a reduction in the solubility of alpha-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. SN - 0364-5134 UR - https://www.unboundmedicine.com/medline/citation/9749615/Glial_cytoplasmic_inclusions_in_white_matter_oligodendrocytes_of_multiple_system_atrophy_brains_contain_insoluble_alpha_synuclein_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0364-5134&date=1998&volume=44&issue=3&spage=415 DB - PRIME DP - Unbound Medicine ER -