The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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
Flagged first, then by citations
Cited by
Sorted by citations
α-Synuclein Locus Triplication Causes Parkinson's Disease
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
α-Synuclein is phosphorylated in synucleinopathy lesions
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
Self-citationMicroglia in neurodegenerative diseases: mechanism and potential therapeutic targets
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”
BackgroundAlpha-synuclein and neurodegenerative diseases
Goedert, M. (2001) · Nature reviews. Neuroscience · doi:10.1038/35081564 · Cited by 1,428
“gov/htbin-post/Omim/dispmim?234200">Hallervorden–Spatz disease ) has also been shown to be immunoreactive for α-synuclei”
BackgroundNeuronal α-Synucleinopathy with Severe Movement Disorder in Mice Expressing A53T Human α-Synuclein
Giasson, B. I., Duda, J. E., Quinn, S. M., Zhang, B., Trojanowski, J. Q., & Lee, V. M.-Y. (2002) · Neuron · doi:10.1016/s0896-6273(02)00682-7 · Cited by 1,266
Self-citationGoedert, M., Spillantini, M. G., Del Tredici, K., & Braak, H. (2013) · Nature Reviews Neurology · doi:10.1038/nrneurol.2012.242 · Cited by 1,190
Luk, K. C., Kehm, V. M., Zhang, B., O’Brien, P., Trojanowski, J. Q., & Lee, V. M. ‐. (2012) · The Journal of Experimental Medicine · doi:10.1084/jem.20112457 · Cited by 1,136
Self-citationEvidence for a Partially Folded Intermediate in α-Synuclein Fibril Formation
Uversky, V. N., Li, J., & Fink, A. L. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m010907200 · Cited by 1,096
Giasson, B. I., Murray, I. V. J., Trojanowski, J. Q., & Lee, V. M.-Y. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008919200 · Cited by 1,080
Self-citationNeuropathological assessment of Parkinson’s disease: refining the diagnostic criteria
Dickson, D. W., Braak, H., Duda, J. E., Duyckaerts, C., Gasser, T., Halliday, G. M., Hardy, J., Leverenz, J. B., Del Tredici, K., Wszolek, Z. K., et al. (2009) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70238-8 · Cited by 972
What does it mean to be natively unfolded?
Uversky, V. N. (2002) · European Journal of Biochemistry · doi:10.1046/j.0014-2956.2001.02649.x · Cited by 1,004
Goedert, M. (2015) · Science · doi:10.1126/science.1255555 · Cited by 1,028
Bendor, J. T., Logan, T. P., & Edwards, R. H. (2013) · Neuron · doi:10.1016/j.neuron.2013.09.004 · Cited by 825
Lee, H.-J., Suk, J.-E., Patrick, C., Bae, E.-J., Cho, J.-H., Rho, S., Hwang, D., Masliah, E., & Lee, S.-J. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.081125 · Cited by 877
Structures of α-synuclein filaments from multiple system atrophy
Schweighauser, M., Shi, Y., Tarutani, A., Kametani, F., Murzin, A. G., Ghetti, B. F., Matsubara, T., Tomita, T., Ando, T., Hasegawa, K., et al. (2020) · Nature · doi:10.1038/s41586-020-2317-6 · Cited by 803
“synuclein inclusions in oligodendrocytes: glial cytoplasmic inclusions (GCIs) or Papp-Lantos bodies (21-25).”
BackgroundSelf-citationConway, K. A., Harper, J. D., & Lansbury, P. T. (2000) · Biochemistry · doi:10.1021/bi991447r · Cited by 786
Murphy, D. D., Rueter, S. M., Trojanowski, J. Q., & Lee, V. M. ‐. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-09-03214.2000 · Cited by 927
“Also, a-synuclein is likely the major component of glial and neuronal inclusions in multiple system atrophy (MSA) and Hallervorden–Spatz disease (Tu et al., 1998).”
BackgroundSelf-citationFiber diffraction of synthetic α-synuclein filaments shows amyloid-like cross-β conformation
Serpell, L. C., Berriman, J. A., Jakes, R., Goedert, M., & Crowther, R. A. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.9.4897 · Cited by 755
Evidence for α-synuclein prions causing multiple system atrophy in humans with parkinsonism
Prusiner, S. B., Woerman, A. L., Mordes, D. A., Watts, J. C., Rampersaud, R., Berry, D. B., Patel, S. S., Oehler, A., Lowe, J. K., Kravitz, S. N., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1514475112 · Cited by 703
“J Neurol Neurosurg Psychiatry 57(6):757–758.”
Distinct α-Synuclein Strains Differentially Promote Tau Inclusions in Neurons
Guo, J. L., Covell, D. J., Daniels, J. P., Iba, M., Stieber, A., Zhang, B., Riddle, D. M., Kwong, L. K., Xu, Y., Trojanowski, J. Q., et al. (2013) · Cell · doi:10.1016/j.cell.2013.05.057 · Cited by 680
Self-citationKahle, P. J., Neumann, M., Ozmen, L., Müller, V., Jacobsen, H., Schindzielorz, A., Okochi, M., Leimer, U., van der Putten, H., Probst, A., et al. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-17-06365.2000 · Cited by 642
“LBs were aSYN-positive in LB variant of Alzheimer’s disease, familial Alzheimer’s disease, and Down’s syndrome (Lippa et al., 1998, 1999; Takeda et al., 1998b ), as well as in neurodegeneration with brain iron accumulation type 1 (formerly known as Hallervorden‐ Spatz disease) (Arawaka et al., 1998; Wakabayashi et al.…”
BackgroundSchulz-Schaeffer, W. J. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0711-0 · Cited by 627
Neuropathology of Parkinson disease
Dickson, D. W. (2018) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2017.07.033 · Cited by 623
α-Synuclein Membrane Interactions and Lipid Specificity
Jo, E., McLaurin, J., Yip, C. M., George‐Hyslop, P. S., & Fraser, P. E. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m004345200 · Cited by 610
Cryo-EM structure of alpha-synuclein fibrils
Guerrero-Ferreira, R., Taylor, N. M. I., Mona, D., Ringler, P., Lauer, M. E., Riek, R., Britschgi, M., & Stahlberg, H. (2018) · eLife · doi:10.7554/elife.36402 · Cited by 615
Alpha-synuclein cortical Lewy bodies correlate with dementia in Parkinson’s disease
Hurtig, H. I., Trojanowski, J. Q., Galvin, J. E., Ewbank, D., Schmidt, M. L., Lee, V. M. Y., Clark, C., Glosser, G., Stern, M. B., Gollomp, S. M., et al. (2000) · Neurology · doi:10.1212/wnl.54.10.1916 · Cited by 604
Self-citationKang, S. H., Li, Y., Fukaya, M., Lorenzini, I., Cleveland, D. W., Ostrow, L. W., Rothstein, J. D., & Bergles, D. E. (2013) · Nature Neuroscience · doi:10.1038/nn.3357 · Cited by 599
Progression and prognosis in multiple system atrophy
Watanabe, H., Saito, Y., Terao, S.-I., Ando, T., Kachi, T., Mukai, E., Aiba, I., Abe, Y., Tamakoshi, A., Doyu, M., et al. (2002) · Brain · doi:10.1093/brain/awf117 · Cited by 596
Cellular milieu imparts distinct pathological α-synuclein strains in α-synucleinopathies
Peng, C., Gathagan, R. J., Covell, D. J., Medellin, C., Stieber, A., Robinson, J. L., Zhang, B., Pitkin, R. M., Olufemi, M. F., Luk, K. C., et al. (2018) · Nature · doi:10.1038/s41586-018-0104-4 · Cited by 605
Self-citationThe Synaptic Function of α-Synuclein
Burré, J. (2015) · Journal of Parkinson s Disease · doi:10.3233/jpd-150642 · Cited by 610
“Since then, -synuclein has been linked to various devastating diseases, including Parkinson’s disease [7, 8], dementia with Lewy bodies [7, 8], multiple system atrophy [9–11], Alzheimer’s disease [12, 13], pantothenate kinase-associated neurodegeneration (PKAN; a.”
BackgroundThe Synucleinopathies: Twenty Years On
Goedert, M., Jakes, R., & Spillantini, M. G. (2017) · Journal of Parkinson s Disease · doi:10.3233/jpd-179005 · Cited by 590
“Similar findings were reported by others at about the same time [73, 74].”
Resultα-Synuclein Shares Physical and Functional Homology with 14-3-3 Proteins
Ostrerova, N., Petrucelli, L., Farrer, M. J., Mehta, N., Choi, P., Hardy, J., & Wolozin, B. L. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-14-05782.1999 · Cited by 560
“Dystrophic neurites in PD and amyotrophic lateral sclerosis show accumulations of a-synuclein, as do glia in multiple systems atrophy (Spillantini et al., 1998; Takeda et al., 1998; Tu et al., 1998). a-Synuclein also accumulates in neuritic plaques in Alzheimer’s disease.”
BackgroundDityrosine Cross-linking Promotes Formation of Stable α-Synuclein Polymers
Souza, J. M., Giasson, B. I., Chen, Q., Lee, V. M. ‐., & Ischiropoulos, H. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m000206200 · Cited by 572
Self-citationThe α‐Synucleinopathies: Parkinson's Disease, Dementia with Lewy Bodies, and Multiple System Atrophy
Spillantini, M. G., & Goedert, M. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb06900.x · Cited by 530
Constitutive Phosphorylation of the Parkinson's Disease Associated α-Synuclein
Okochi, M., Walter, J., Koyama, A., Nakajo, S., Baba, M., Iwatsubo, T., Meijer, L., Kahle, P. J., & Haass, C. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.1.390 · Cited by 535
Self-citationWakabayashi, K., Tanji, K., Mori, F., & Takahashi, H. (2007) · Neuropathology · doi:10.1111/j.1440-1789.2007.00803.x · Cited by 544
Giasson, B. I., Uryu, K., Trojanowski, J. Q., & Lee, V. M. ‐. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.12.7619 · Cited by 510
Self-citationUversky, V. N. (2003) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2003.10506918 · Cited by 516
The Lewy Body in Parkinson’s Disease and Related Neurodegenerative Disorders
Wakabayashi, K., Tanji, K., Odagiri, S., Miki, Y., Mori, F., & Takahashi, H. (2012) · Molecular Neurobiology · doi:10.1007/s12035-012-8280-y · Cited by 507
Wenning, G. K., Colosimo, C., Geser, F., & Poewe, W. H. (2004) · The Lancet Neurology · doi:10.1016/s1474-4422(03)00662-8 · Cited by 470
Galvin, J. E., Lee, V. M. ‐., & Trojanowski, J. Q. (2001) · Archives of Neurology · doi:10.1001/archneur.58.2.186 · Cited by 473
“Significantly, aS has been implicated as a major component of the tubulofilamentous inclusions found in oligodendrocytes in multiple system atrophy known as glial cytoplasmic inclusions (GCIs).(2,3,5,6,28) Multiple system atrophy consists of a syndrome complex with parkinsonism and a combination of cerebellar, autonom…”
BackgroundResultSelf-citationBraak, H., Sastre, M., & Del Tredici, K. (2007) · Acta Neuropathologica · doi:10.1007/s00401-007-0244-3 · Cited by 462
“attention, although their occurrence in PD/DLB has been repeatedly reported by previous authors [1, 2, 12, 23, 30, 31, 46, 51, 61, 66, 67, 71, 72].”
ResultLee, F. J. S., Liu, F., Pristupa, Z. B., & Niznik, H. B. (2001) · The FASEB Journal · doi:10.1096/fj.00-0334com · Cited by 463
Wakabayashi, K., Hayashi, S., Yoshimoto, M., Kudo, H., & Takahashi, H. (2000) · Acta Neuropathologica · doi:10.1007/pl00007400 · Cited by 451
Transmission of multiple system atrophy prions to transgenic mice
Watts, J. C., Giles, K., Oehler, A., Middleton, L. T., Dexter, D. T., Gentleman, S., DeArmond, S. J., & Prusiner, S. B. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1318268110 · Cited by 455
“Proc Natl Acad Sci USA 108(6):2528–2533.”
Interaction of Human α-Synuclein and Parkinson's Disease Variants with Phospholipids
Perrin, R. J., Woods, W. S., Clayton, D. F., & George, J. M. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m004851200 · Cited by 444
Phosphorylated α-Synuclein Is Ubiquitinated in α-Synucleinopathy Lesions
Hasegawa, M., Fujiwara, H., Nonaka, T., Wakabayashi, K., Takahashi, H., Lee, V. M.-Y., Trojanowski, J. Q., Mann, D., & Iwatsubo, T. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m208046200 · Cited by 428
Self-citationNEURODEGENERATIVE DISEASES: New Concepts of Pathogenesis and Their Therapeutic Implications
Skovronsky, D., Lee, V. M. ‐., & Trojanowski, J. Q. (2006) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev.pathol.1.110304.100113 · Cited by 433
Self-citationGalvin, J. E., Uryu, K., Lee, V. M. ‐., & Trojanowski, J. Q. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.23.13450 · Cited by 430
Self-citationThe E46K Mutation in α-Synuclein Increases Amyloid Fibril Formation
Greenbaum, E. A., Graves, C. L., Mishizen-Eberz, A. J., Lupoli, M. A., Lynch, D. R., Englander, S. W., Axelsen, P. H., & Giasson, B. I. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m411638200 · Cited by 388
Self-citationRole of α-Synuclein Carboxy-Terminus on Fibril Formation in Vitro
Murray, I. V. J., Giasson, B. I., Quinn, S. M., Koppaka, V., Axelsen, P. H., Ischiropoulos, H., Trojanowski, J. Q., & Lee, V. M. ‐. (2003) · Biochemistry · doi:10.1021/bi027363r · Cited by 372
Self-citationProposed neuropathological criteria for the post mortem diagnosis of multiple system atrophy
Trojanowski, J. Q., Revesz, T., & the Neuropathology Working Group on MSA (2007) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2007.00907.x · Cited by 349
Self-citationMutations in COQ2 in Familial and Sporadic Multiple-System Atrophy
The Multiple-System Atrophy Research Collaboration (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1212115 · Cited by 342
Human Astrocytes Transfer Aggregated Alpha-Synuclein via Tunneling Nanotubes
Rostami, J., Holmqvist, S., Lindström, V., Sigvardson, J., Westermark, G. T., Ingelsson, M., Bergström, J., Roybon, L., & Erlandsson, A. (2017) · The Journal of Neuroscience · doi:10.1523/jneurosci.0983-17.2017 · Cited by 339
“…an unexpected role of astrocytes in the propagation of -SYN pathology via TNTs, revealing astrocytes as a potential target for therapeutic intervention. advanced disease stages (Tu et al., 1998; Wakabayashi et al., 2000; Terada et al., 2003; Croisier and Graeber, 2006; Braak et al., 2007).”
BackgroundIgaz, L. M., Kwong, L. K., Xu, Y., Truax, A. C., Uryu, K., Neumann, M., Clark, C. M., Elman, L. B., Miller, B. L., Grossman, M., et al. (2008) · American Journal Of Pathology · doi:10.2353/ajpath.2008.080003 · Cited by 332
Self-citationBiophysics of Parkinsons Disease: Structure and Aggregation of α- Synuclein
Uversky, V. N., & Eliezer, D. (2009) · Current Protein and Peptide Science · doi:10.2174/138920309789351921 · Cited by 325
Hyperphosphorylation and insolubility of α‐synuclein in transgenic mouse oligodendrocytes
Kahle, P. J., Neumann, M., Ozmen, L., Müller, V., Jacobsen, H., Spooren, W., Fuss, B., Mallon, B., Macklin, W. B., Fujiwara, H., et al. (2002) · The EMBO Reports · doi:10.1093/embo-reports/kvf109 · Cited by 314
Self-citationUversky, V. N. (2003) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-003-3096-6 · Cited by 322
Widespread Alterations of α-Synuclein in Multiple System Atrophy
Dickson, D. W., Liu, W.-K., Hardy, J., Farrer, M. J., Mehta, N. D., Uitti, R. J., Mark, M. H., Zimmerman, T., Golbe, L. I., Sage, J., et al. (1999) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)65226-1 · Cited by 298
Yazawa, I., Giasson, B. I., Sasaki, R., Zhang, B., Joyce, S., Uryu, K., Trojanowski, J. Q., & Lee, V. M.-Y. (2005) · Neuron · doi:10.1016/j.neuron.2005.01.032 · Cited by 301
Self-citationα-Synuclein pathology in Parkinson’s disease and related α-synucleinopathies
Henderson, M. X., Trojanowski, J. Q., & Lee, V. M. ‐. (2019) · Neuroscience Letters · doi:10.1016/j.neulet.2019.134316 · Cited by 301
Self-citationGenomic Rearrangements and Gene Copy-Number Alterations as a Cause of Nervous System Disorders
Lee, J. A., & Lupski, J. R. (2006) · Neuron · doi:10.1016/j.neuron.2006.09.027 · Cited by 288
“…(Maraganore et al., 2006). a-Synuclein is a small synaptic protein found to be a major component of Lewy bodies (LBs) and Lewy neurites, which are the pathologic hallmarks of sporadic PD and dementia with LBs (DLB), and glial cell cytoplasmic inclusions (Spillantini et al., 1997; Tu et al., 1998).”
Functional Consequences of α-Synuclein Tyrosine Nitration
Hodara, R., Norris, E. H., Giasson, B. I., Mishizen-Eberz, A. J., Lynch, D. R., Lee, V. M. ‐., & Ischiropoulos, H. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m408906200 · Cited by 296
Self-citationMutation E46K increases phospholipid binding and assembly into filaments of human α‐synuclein
Choi, W., Zibaee, S., Jakes, R., Serpell, L. C., Davletov, B. A., Crowther, R. A., & Goedert, M. (2004) · FEBS Letters · doi:10.1016/j.febslet.2004.09.038 · Cited by 292
Exposure to Long Chain Polyunsaturated Fatty Acids Triggers Rapid Multimerization of Synucleins
Perrin, R. J., Woods, W. S., Clayton, D. F., & George, J. M. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m105022200 · Cited by 283
Widespread Nitration of Pathological Inclusions in Neurodegenerative Synucleinopathies
Duda, J. E., Giasson, B. I., Chen, Q., Gur, T., Hurtig, H. I., Stern, M. B., Gollomp, S. M., Ischiropoulos, H., Lee, V. M. ‐., & Trojanowski, J. Q. (2000) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64781-5 · Cited by 276
Self-citationNorris, E. H., Giasson, B. I., Hodara, R., Xu, S., Trojanowski, J. Q., Ischiropoulos, H., & Lee, V. M.-Y. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m412621200 · Cited by 273
Self-citationAlpha-synuclein cell-to-cell transfer and seeding in grafted dopaminergic neurons in vivo
Angot, E., Steiner, J. A., Lema Tomé, C. M., Ekström, P., Mattsson, B., Björklund, A., & Brundin, P. (2012) · PLoS ONE · doi:10.1371/journal.pone.0039465 · Cited by 270
Neuropathology of synuclein aggregates
Duda, J. E., Lee, V. M. ‐., & Trojanowski, J. Q. (2000) · Journal of Neuroscience Research · doi:10.1002/1097-4547(20000715)61:2 · Cited by 263
Self-citationInterface between tauopathies and synucleinopathies: A tale of two proteins
Galpern, W. R., & Lang, A. E. (2006) · Annals of Neurology · doi:10.1002/ana.20819 · Cited by 267
Biochemical Characterization of the Core Structure of α-Synuclein Filaments
Miake, H., Mizusawa, H., Iwatsubo, T., & Hasegawa, M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m110551200 · Cited by 266
Self-citationFyn kinase regulates misfolded α-synuclein uptake and NLRP3 inflammasome activation in microglia
Panicker, N., Sarkar, S., Harischandra, D. S., Neal, M. P., Kam, T., Jin, H., Saminathan, H., Langley, M. R., Charli, A., Samidurai, M., et al. (2019) · The Journal of Experimental Medicine · doi:10.1084/jem.20182191 · Cited by 257
“…is an active area of investigation; in patients with multiple system atrophy, αSyn accumulates in oligodendrocytes as glial cytoplasmic inclusions (Tu et al., 1998) and can seed endogenous αSyn aggregation with even greater potency than neuronal αSyn (Peng et al., 2018). αSyn uptake in neurons…”
BackgroundHDL and cholesterol handling in the brain
Vitali, C., Wellington, C. L., & Calabresi, L. (2014) · Cardiovascular Research · doi:10.1093/cvr/cvu148 · Cited by 254
Propagation of prions causing synucleinopathies in cultured cells
Woerman, A. L., Stöhr, J., Aoyagi, A., Rampersaud, R., Krejciova, Z., Watts, J. C., Ohyama, T., Patel, S. S., Widjaja, K., Oehler, A., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1513426112 · Cited by 250
“Although no LBs were found, abundant immunostaining in the cytoplasm of glial cells was identified (8, 10, 11).”
BackgroundBenskey, M. J., Perez, R. G., & Manfredsson, F. P. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13570 · Cited by 257
Environmental Exposures and Gene Regulation in Disease Etiology
Edwards, T. M., & Myers, J. P. (2007) · Environmental Health Perspectives · doi:10.1289/ehp.9951 · Cited by 242
Lindström, V., Gustafsson, G., Sanders, L. H., Howlett, E. H., Sigvardson, J., Kasrayan, A., Ingelsson, M., Bergström, J., & Erlandsson, A. (2017) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2017.04.009 · Cited by 233
“Although α-synuclein deposits are primarily found in neurons, they also appear frequently in astrocytes at advanced disease stages (Braak et al., 2007; Croisier and Graeber, 2006; Terada et al., 2003; Tu et al., 1998; Wakabayashi et al., 2000).”
BackgroundMolecular mechanisms of α-synuclein neurodegeneration
Waxman, E. A., & Giasson, B. I. (2008) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2008.09.013 · Cited by 247
Self-citationα-Synuclein Overexpression Protects against Paraquat-Induced Neurodegeneration
Manning-Bog, A., McCormack, A. L., Purisai, M. G., Bolin, L. M., & Monte, D. A. D. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-08-03095.2003 · Cited by 242
“…(Conway et al., 1998; Giasson et al., 1999) is likely to explain, at least in part, its involvement in the formation of intracellular inclusions typical of diseases such as Parkinson’s disease (PD), dementia with Lewy bodies, and multiple system atrophy (Spillantini et al., 1998; Tu et al., 1998).”
BackgroundThe role of alpha-synuclein in neurotransmission and synaptic plasticity
Cheng, F., Vivacqua, G., & Yu, S. (2010) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2010.12.001 · Cited by 245
“The central hydrophobic NAC region of a-syn was initially identified from the AD brains as the non-b-amyloid component of the AD amyloid (Uéda et al., 1993).”
InfluentialNeumann, M., Kwong, L. K., Truax, A. C., Vanmassenhove, B., Kretzschmar, H. A., Deerlin, V. M. V., Clark, C. M., Grossman, M., Miller, B. L., Trojanowski, J. Q., et al. (2007) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/01.jnen.0000248554.45456.58 · Cited by 238
“Furthermore, >-synuclein- and tau-positive glial inclusions in MSA, PSP, and CBD were TDP-43-negative, and no TDP-43-positive inclusions were detectable in PSP, CBD, and MSA, thereby demonstrating specificity of the TDP-43 glial inclusions described in this study for FTLD-U.”
BackgroundSelf-citationIntrinsic disorder in proteins associated with neurodegenerative diseases
Vladimir, N. (2009) · Frontiers in bioscience · doi:10.2741/3594 · Cited by 241
Jo, E., Fuller, N., Rand, R. P., George‐Hyslop, P. S., & Fraser, P. E. (2002) · Journal of Molecular Biology · doi:10.1006/jmbi.2001.5269 · Cited by 238
Astrocytes have the capacity to act as antigen-presenting cells in the Parkinson’s disease brain
Rostami, J., Fotaki, G., Sirois, J., Mzezewa, R., Bergström, J., Essand, M., Healy, L., & Erlandsson, A. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01776-7 · Cited by 212
Cell death mechanisms in Parkinson's disease
Jellinger, K. A. (2000) · Journal of Neural Transmission · doi:10.1007/s007020050001 · Cited by 227
Campbell, B. C. V., McLean, C., Culvenor, J. G., Gai, W., Blumbergs, P. C., Jäkälä, P., Beyreuther, K. T., Masters, C. L., & Li, Q. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00021.x · Cited by 226
Mice lacking alpha-synuclein are resistant to mitochondrial toxins
Klivènyi, P., Siwek, D. F., Gardian, G., Yang, L., Starkov, A. A., Cléren, C., Ferrante, R. J., Kowall, N. W., Abeliovich, A., & Beal, M. F. (2005) · Neurobiology of Disease · doi:10.1016/j.nbd.2005.08.018 · Cited by 216
“…associated with dominantly inherited PD, and that a-synuclein appears to be the most abundant protein in Lewy bodies (Polymeropoulos et al., 1997; Spillantini et al., 1998; Kruger et al., 1999). a-Synuclein is also part of glial cytoplasmic inclusions of multiple system atrophy (Tu et al., 1998).”
Multiple System Atrophy: A Sporadic Synucleinopathy
Dickson, D. W., Lin, W.-L., Liu, W.-K., & Yen, S.-H. C. (1999) · Brain Pathology · doi:10.1111/j.1750-3639.1999.tb00553.x · Cited by 212
“biochemical changes of -synuclein in MSA (72), and it also suggested changes in solubility of -synuclein.”
BackgroundSpecificity and Regulation of Casein Kinase-Mediated Phosphorylation of ??-Synuclein
Waxman, E. A., & Giasson, B. I. (2008) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3186fc995 · Cited by 241
Self-citationStefanova, N., Reindl, M., Neumann, M., Haass, C., Poewe, W., Kahle, P. J., & Wenning, G. K. (2005) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)62307-3 · Cited by 208
Tong, J., Wong, H., Guttman, M., Ang, L. C., Forno, L. S., Shimadzu, M., Rajput, A. H., Muenter, M. D., Kish, S. J., Hornykiewicz, O., et al. (2009) · Brain · doi:10.1093/brain/awp282 · Cited by 210
“and are consistent with previous findings of Tu et al. (1998) and”
ResultZhou, W., Hurlbert, M. S., Schaack, J. B., Prasad, K. N., & Freed, C. R. (2000) · Brain Research · doi:10.1016/s0006-8993(00)02215-0 · Cited by 207
α-Synuclein: Normal Function and Role in Neurodegenerative Diseases
Norris, E. H., Giasson, B. I., & Lee, V. M. ‐. (2004) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/s0070-2153(04)60002-0 · Cited by 208
Self-citationGlia and alpha-synuclein in neurodegeneration: A complex interaction
Brück, D., Wenning, G. K., Stefanova, N., & Fellner, L. (2015) · Neurobiology of Disease · doi:10.1016/j.nbd.2015.03.003 · Cited by 213
“…Ubhi et al., 2010) Augmented neurodegeneration Altered levels of oxidized and nitrated AS (Ubhi et al., 2009) namely AS (Papp et al., 1989; Kato and Nakamura, 1990; Kato et al., 1991; Papp and Lantos, 1992; Arima et al., 1998; Spillantini et al., 1998; Tu et al., 1998; Wakabayashi et al., 1998).”
Tubulin Seeds α-Synuclein Fibril Formation
Alim, M., Hossain, M. S., Arima, K., Takeda, K., Izumiyama, Y., Nakamura, M., Kaji, H., Shinoda, T., Hisanaga, S., & Uéda, K. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m102981200 · Cited by 204
The role of α-synuclein in neurodegenerative diseases
Bennett, M. C. (2004) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2004.10.010 · Cited by 198
Yu, S., Li, X., Liu, G., Han, J., Zhang, C., Li, Y., Xu, S., Liu, C., Gao, Y., Yang, H., et al. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2006.12.028 · Cited by 202
Galvin, J. E., Giasson, B. I., Hurtig, H. I., Lee, V. M. ‐., & Trojanowski, J. Q. (2000) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64548-8 · Cited by 193
Self-citation
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
