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Glial cytoplasmic inclusions in white matter oligodendrocytes of multiple system atrophy brains contain insoluble α‐synuclein
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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“MSA is a synucleinopathy, however, unlike PD and dementia with Lewy bodies, in which α-syn accumulates and aggregates in neurons, MSA is characterized neuropathologically by α-syn-positive glial cytoplasmic inclusions (GCIs) in oligodendroglia [1, 42, 54, 58, 59].”
From Novel oligodendroglial alpha synuclein viral vector models of multiple system atrophy: studies in rodents and nonhuman primates (2017) · cites this paper as [54]
In the citing paper
“The pathological hallmark of MSA is the abnormal accumulation of α-syn in the cytoplasm of oligodendrocytes, named glial cytoplasmic inclusions (GCIs).271–275”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [272]
Citations
Cites
Spillantini, M. G., Schmidt, M. L., Lee, V. M.-Y., Trojanowski, J. Q., Jakes, R., & Goedert, M. (1997) · Nature · doi:10.1038/42166 · Cited by 8,382
Self-citationMutation in the α-Synuclein Gene Identified in Families with Parkinson's Disease
Polymeropoulos, M. H., Lavedan, C., Leroy, E., Ide, S. E., Dehejia, A., Dutra, A., Pike, B., Root, H., Rubenstein, J., Boyer, R., et al. (1997) · Science · doi:10.1126/science.276.5321.2045 · Cited by 8,240
AlaSOPro mutation in the gene encoding α-synuclein in Parkinson's disease
Krüger, R., Kuhn, W., Müller, T., Woitalla, D., Graeber, M., Kösel, S., Przuntek, H., Epplen, J. T., Schols, L., & Riess, O. (1998) · Nature Genetics · doi:10.1038/ng0298-106 · Cited by 3,836
Spillantini, M. G., Crowther, R. A., Jakes, R., Hasegawa, M., & Goedert, M. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.11.6469 · Cited by 2,868
Synuclein: a neuron-specific protein localized to the nucleus and presynaptic nerve terminal
Maroteaux, L., Campanelli, J., & Scheller, R. (1988) · Journal of Neuroscience · doi:10.1523/jneurosci.08-08-02804.1988 · Cited by 1,646
(1998) · Europe PMC (PubMed Central) · Cited by 1,594
Self-citationMolecular cloning of cDNA encoding an unrecognized component of amyloid in Alzheimer disease.
Uéda, K., Fukushima, H., Masliah, E., Xia, Y., Iwai, A., Yoshimoto, M., Otero, D. A., Kondo, J. D. M., Ihara, Y., & Saitoh, T. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.23.11282 · Cited by 1,502
Iwai, A., Masliah, E., Yoshimoto, M., Ge, N., Flanagan, L., Rohan de Silva, H. A., Kittel, A., & Saitoh, T. (1995) · Neuron · doi:10.1016/0896-6273(95)90302-x · Cited by 1,316
Identification of two distinct synucleins from human brain
Jakes, R., Spillantini, M. G., & Goedert, M. (1994) · FEBS Letters · doi:10.1016/0014-5793(94)00395-5 · Cited by 1,080
Papp, M. I., Kahn, J. E., & Lantos, P. L. (1989) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(89)90219-0 · Cited by 991
George, J. M., Jin, H., Woods, W. S., & Clayton, D. F. (1995) · Neuron · doi:10.1016/0896-6273(95)90040-3 · Cited by 844
Multiple system atrophy: A review of 203 pathologically proven cases
Wenning, G. K., Tison, F., Ben‐Shlomo, Y., Daniel, S. E., & Quinn, N. P. (1997) · Movement Disorders · doi:10.1002/mds.870120203 · Cited by 802
Abnormal accumulation of NACP/alpha-synuclein in neurodegenerative disorders.
Takeda, A., Mallory, M. E., Sundsmo, M. P., Honer, W. G., Hansen, L. A., & Masliah, E. (1998) · Europe PMC (PubMed Central) · Cited by 403
Irizarry, M. C., Growdon, W., Gómez‐Isla, T., Newell, K. L., George, J. M., Clayton, D. F., & Hyman, B. T. (1998) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199804000-00005 · Cited by 394
Spillantini, M. G., Goedert, M., Crowther, R. A., Murrell, J. R., Farlow, M. R., & Ghetti, B. F. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.8.4113 · Cited by 339
The rat brain synucleins; family of proteins transiently associated with neuronal membrane
Maroteaux, L., & Scheller, R. H. (1991) · Molecular Brain Research · doi:10.1016/0169-328x(91)90043-w · Cited by 334
NACP, a presynaptic protein, immunoreactivity in Lewy bodies in Parkinson's disease
Wakabayashi, K., Matsumoto, K., Takayama, K., Yoshimoto, M., & Takahashi, H. (1997) · Neuroscience Letters · doi:10.1016/s0304-3940(97)00891-4 · Cited by 331
Identification of a breast cancer-specific gene, BCSG1, by direct differential cDNA sequencing.
Ji, H. W., Liu, Y. E., Jia, T., Wang, M., Liu, J., Xiao, G., Joseph, B. K., Rosen, C. A., & Shi, Y. (1997) · PubMed · Cited by 327
Trojanowski, J. Q., Goedert, M., Iwatsubo, T., & Lee, V. M. ‐. (1998) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4400432 · Cited by 297
Self-citationNeurodegenerative disorders with extensive tau pathology: A comparative study and review
Feany, M. Β., & Dickson, D. W. (1996) · Annals of Neurology · doi:10.1002/ana.410400204 · Cited by 280
Lewy Bodies of Parkinson's Disease Contain Neurofilament Antigens
Goldman, J. E., Yen, S.-H. C., Chiu, F., & Peress, N. S. (1983) · Science · doi:10.1126/science.6308771 · Cited by 268
Aggregation of Neurofilament and α-Synuclein Proteins in Lewy Bodies
Trojanowski, J. Q., & Lee, V. M. (1998) · Archives of Neurology · doi:10.1001/archneur.55.2.151 · Cited by 257
Self-citationDalchau, R., Kirkley, J., & Fabre, J. W. (1980) · European Journal of Immunology · doi:10.1002/eji.1830101003 · Cited by 233
Glial Inclusions in CNS Degenerative Diseases
Chin, S., & Goldman, J. E. (1996) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199605000-00001 · Cited by 210
Irizarry, M. C., Kim, T., McNamara, M. J., Tanzi, R. E., George, J. M., Clayton, D. F., & Hyman, B. T. (1996) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199608000-00004 · Cited by 205
A new brain‐specific 14‐kDa protein is a phosphoprotein
Nakajo, S., TSUKADA, K., Omata, K., Nakamura, Y., & Nakaya, K. (1993) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1993.tb18337.x · Cited by 170
Self-citationLEE, V. M.-Y., Page, C. D., Wu, H. ‐., & Schlaepfer, W. W. (1984) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1984.tb09692.x · Cited by 163
Self-citationEpitope map of neurofilament protein domains in cortical and peripheral nervous system Lewy bodies.
Schmidt, M. L., Murray, J., Lee, V. M. Y., Hill, W. D., Wertkin, A. M., & Trojanowski, J. Q. (1991) · PubMed Central · Cited by 161
Self-citationThe Molecular and Genetic Basis of Neurological Disease.
BARKER, R. (1998) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.65.5.806a · Cited by 158
Jensen, P. H., Højrup, P., Hager, H., Nielsen, M. S., JACOBSEN, L., Olesen, O. F., Gliemann, J., & Jakes, R. (1997) · Biochemical Journal · doi:10.1042/bj3230539 · Cited by 143
An Improved Approach to Prepare Human Brains for Research
Vonsattel, J. P., Aizawa, H., DiFiglia, M., McKee, A. C., MacDonald, M. E., Gusella, J. F., Landwehrmeyer, G. B., Bird, E. D., Richardson, E. P., & Hedley‐Whyte, E. T. (1995) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199501000-00006 · Cited by 134
Shibayama‐Imazu, T., Okahashi, I., Omata, K., Nakajo, S., Ochiai, H., Nakai, Y., Hama, T., Nakamura, Y., & Nakaya, K. (1993) · Brain Research · doi:10.1016/0006-8993(93)90796-p · Cited by 117
Self-citationAssignment of Human α-Synuclein (SNCA) and β-Synuclein (SNCB) Genes to Chromosomes 4q21 and 5q35
Spillantini, M. G., Divane, A., & Goedert, M. (1995) · Genomics · doi:10.1006/geno.1995.1063 · Cited by 108
Purification and Characterization of a Novel Brain‐Specific 14‐kDa Protein
Nakajo, S., Omata, K., Aiuchi, T., Shibayama, T., Okahashi, I., Ochiai, H., Nakai, Y., Nakaya, K., & Nakamura, Y. (1990) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1990.tb05792.x · Cited by 108
Self-citationHill, W., Lee, V. M. ‐., Hurtig, H. I., Murray, J. M., & Trojanowski, J. Q. (1991) · The Journal of Comparative Neurology · doi:10.1002/cne.903090111 · Cited by 107
Self-citationGoedert, M. (1997) · Nature · doi:10.1038/40767 · Cited by 95
Cairns, N. J., Atkinson, P. F., Hanger, D. P., Anderton, B. H., Daniel, S. E., & Lantos, P. L. (1997) · Neuroscience Letters · doi:10.1016/s0304-3940(97)00474-6 · Cited by 85
Tu, P., Robinson, K. A., Snoo, F. D., Eyer, J., Peterson, A. C., Lee, V. M. ‐., & Trojanowski, J. Q. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-03-01064.1997 · Cited by 62
Self-citationMonoclonal antibodies to purified cortical lewy bodies recognize the mid‐size neurofilament subunit
Galvin, J. E., Lee, V. M. ‐., Baba, M., Mann, D. M. A., Dickson, D. W., Yamaguchi, H., Schmidt, M. L., Iwatsubo, T., & Trojanowski, J. Q. (1997) · Annals of Neurology · doi:10.1002/ana.410420410 · Cited by 51
Self-citationKim, S. U., McMorris, F. A., & Sprinkle, T. J. (1984) · Brain Research · doi:10.1016/0006-8993(84)91360-x · Cited by 32
Arai, N., Nishimura, M., Oda, M., Morimatsu, Y., Ohe, R., & Nagatomo, H. (1992) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(92)90101-p · Cited by 31
Tamaoka, A., Mizusawa, H., Mori, H., & Shoji, S.-I. (1995) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(94)00275-s · Cited by 28
Nakajo, S., Tsukada, K., Kameyama, H., Furuyama, Y., & Nakaya, K. (1996) · Brain Research · doi:10.1016/s0006-8993(96)00914-6 · Cited by 27
Self-citation
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Singleton, A. B., Farrer, M., Johnson, J., Singleton, A., Hague, S., Kachergus, J., Hulihan, M., Peuralinna, T., Dutra, A., Nussbaum, R., et al. (2003) · Science · doi:10.1126/science.1090278 · Cited by 4,383
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Fujiwara, H., Hasegawa, M., Dohmae, N., Kawashima, A., Masliah, E., Goldberg, M. S., Shen, J., Takio, K., & Iwatsubo, T. (2002) · Nature Cell Biology · doi:10.1038/ncb748 · Cited by 2,174
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Gao, C., Jiang, J., Tan, Y., & Chen, S. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01588-0 · Cited by 1,616
Giasson, B. I., Duda, J. E., Murray, I. V. J., Chen, Q., Souza, J. M., Hurtig, H. I., Ischiropoulos, H., Trojanowski, J. Q., & Lee, V. M. ‐. (2000) · Science · doi:10.1126/science.290.5493.985 · Cited by 1,567
Self-citationConway, K. A., Harper, J. D., & Lansbury, P. T. (1998) · Nature Medicine · doi:10.1038/3311 · Cited by 1,520
“and from filamentous inclusions characteristic of multiple system atroph”
Background
Metadata
- 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.
- ORCID
- 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 › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › 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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