Hyperphosphorylation and insolubility of α‐synuclein in transgenic mouse oligodendrocytes
Open accessAbstract
(Oligodendro)glial cytoplasmic inclusions composed of alpha-synuclein (alpha SYN) characterize multiple system atrophy (MSA). Mature oligodendrocytes (OLs) do not normally express alpha SYN, so MSA pathology may arise from aberrant expression of alpha SYN in OLs. To study pathological deposition of alpha SYN in OLs, transgenic mice were generated in which human wild-type alpha SYN was driven by a proteolipid protein promoter. Transgenic alpha SYN was detected in OLs but no other brain cell type. At the light microscopic level, the transgenic alpha SYN profiles resembled glial cytoplasmic inclusions. Strikingly, the diagnostic hyperphosphorylation at S129 of alpha SYN was reproduced in the transgenic mice. A significant proportion of the transgenic alpha SYN was detergent insoluble, as in MSA patients. The histological and biochemical abnormalities were specific for the disease-relevant alpha SYN because control green fluorescent protein was fully soluble and evenly distributed throughout OL cell bodies and processes. Thus, ectopic expression alpha SYN in OLs might initiate salient features of MSA pathology.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Transgenic mouse models overexpressing human α-syn under oligodendroglia-specific promoters such as PLP, MBP, and CNP have been developed to study MSA.
“Transgenic (tg) mouse models overexpressing human α-syn under different oligodendroglia-specific promoters, such as proteolipid protein (PLP) [31], myelin basic protein (MBP) [51], and 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNP) [67], have been developed to study MSA.”
From Novel oligodendroglial alpha synuclein viral vector models of multiple system atrophy: studies in rodents and nonhuman primates (2017) · cites this paper as [31]
Currently available animal models of MSA are limited to 3 transgenic mouse lines overexpressing human α-syn under PLP, MBP, and CNP promoters.
“Currently available animal models of MSA are limited to 3 tg mouse lines overexpressing human α-syn under proteolipid protein (PLP) promoter [31], myelin basic protein (MBP) promoter [51], and 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNP) promoter [67].”
From Novel oligodendroglial alpha synuclein viral vector models of multiple system atrophy: studies in rodents and nonhuman primates (2017) · cites this paper as [31]
Initial studies using PLP-driven expression reported formation of GCIs, but demyelination and neurodegeneration were lacking.
“Initial studies using PLP-driven expression reported formation of GCIs, however demyelination and neurodegeneration was lacking [31].”
From Novel oligodendroglial alpha synuclein viral vector models of multiple system atrophy: studies in rodents and nonhuman primates (2017) · cites this paper as [31]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Manipulating the mouse embryo: A laboratory manual
Hogan, B., Costantini, F. D., & Lacy, E. (1986) · Cited by 4,467 · see citing works
Manipulating the Mouse Embryo: A Laboratory Manual
Behringer, R. R., Gertsenstein, M., Nagy, K. V., & Nagy, A. (2002) · Cited by 2,046 · see citing works
α-Synuclein is phosphorylated in synucleinopathy lesions
Fujiwara, H., Hasegawa, M., Dohmae, N., Kawashima, A., Masliah, E., Goldberg, M., Shen, J., Takio, K., & Iwatsubo, T. (2002) · Nature Cell Biology · doi:10.1038/ncb748 · Cited by 1,906 · see citing works
Self-citationGiasson, 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 1,551 · see citing works
Consensus statement on the diagnosis of multiple system atrophy
Gilman, S., Low, P. A., Quinn, N. P., Albanese, A., Ben‐Shlomo, Y., Fowler, C. J., Kaufmann, H., Klockgether, T., Lang, A. E., Lantos, P. L., et al. (1998) · Clinical Autonomic Research · doi:10.1007/bf02309628 · Cited by 1,316 · see citing works
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 · see citing works
Spillantini, M. G., Crowther, R. A., Jakes, R., Cairns, N. J., Lantos, P. L., & Goedert, M. (1998) · Neuroscience Letters · doi:10.1016/s0304-3940(98)00504-7 · Cited by 1,026 · see citing works
Consensus statement on the diagnosis of multiple system atrophy
Gilman, S., Low, P. A., Quinn, N. P., Albanese, A., Ben‐Shlomo, Y., Fowler, C. J., Kaufmann, H., Klockgether, T., Lang, A. E., Lantos, P. L., et al. (1999) · Journal of the Neurological Sciences · doi:10.1016/s0022-510x(98)00304-9 · Cited by 915 · see citing works
Tu, P., Galvin, J. E., Baba, M., Giasson, B., Tomita, T., Leight, S., Nakajo, S., Iwatsubo, T., Trojanowski, J. Q., & Lee, V. M. ‐. (1998) · Annals of Neurology · doi:10.1002/ana.410440324 · Cited by 686 · see citing works
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 641 · see citing works
Self-citationConstitutive 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 521 · see citing works
Self-citationMicroscopic analysis of polymerization dynamics with individual actin filaments
Fujiwara, I., Takahashi, S., Tadakuma, H., Funatsu, T., & Ishiwata, S. (2002) · Nature Cell Biology · doi:10.1038/ncb841 · Cited by 420 · see citing works
Synucleins Are a Novel Class of Substrates for G Protein-coupled Receptor Kinases
Pronin, A. N., Morris, A. J., Surguchov, A. P., & Benovic, J. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m003542200 · Cited by 388 · see citing works
Mallon, B. S., Shick, H. E., Kidd, G. J., & Macklin, W. B. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-03-00876.2002 · Cited by 382 · see citing works
Self-citationWidespread 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 · see citing works
Arima, K., Uéda, K., Sunohara, N., Arakawa, K., Hirai, S., Nakamura, M., Tonozuka-Uehara, H., & Kawai, M. (1998) · Acta Neuropathologica · doi:10.1007/s004010050917 · Cited by 239 · see citing works
Kahle, P. J., Neumann, M., Ozmen, L., Müller, V., Odoy, S., Okamoto, N., Jacobsen, H., Iwatsubo, T., Trojanowski, J. Q., Takahashi, H., et al. (2001) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63072-6 · Cited by 239 · see citing works
Self-citationCampbell, 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 221 · see citing works
The Definition of Multiple System Atrophy
Lantos, P. L. (1998) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199812000-00001 · Cited by 199 · see citing works
Starnberg Trial on Epidemiology of Parkinsonism and Hypertension in the Elderly
Trenkwalder, C. (1995) · Archives of Neurology · doi:10.1001/archneur.1995.00540340109020 · Cited by 158 · see citing works
Duda, J. E., Giasson, B. I., Gur, T., Montine, T. J., Robertson, D., Biaggioni, I., Hurtig, H. I., Stern, M. B., Gollomp, S. M., Grossman, M., et al. (2000) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/59.9.830 · Cited by 150 · see citing works
Gai, W. P., Power, J. H., Blumbergs, P. C., Culvenor, J. G., & Jensen, P. H. (1999) · PubMed · Cited by 136 · see citing works
Fuss, B., Mallon, B. S., Phan, T., Ohlemeyer, C., Kirchhoff, F., Nishiyama, A., & Macklin, W. B. (2000) · Developmental Biology · doi:10.1006/dbio.1999.9574 · Cited by 130 · see citing works
Self-citationGai, W. P., Power, J. H. T., Blumbergs, P. C., Culvenor, J. G., & Jensen, P. H. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.02093.x · Cited by 122 · see citing works
Ozawa, T., Okuizumi, K., Ikeuchi, T., Wakabayashi, K., Takahashi, H., & Tsuji, S. (2001) · Acta Neuropathologica · doi:10.1007/s004010100367 · Cited by 109 · see citing works
Hanna, P. A., Jankovic, J. J., & Kirkpatrick, J. B. (1999) · Archives of Neurology · doi:10.1001/archneur.56.1.90 · Cited by 82 · see citing works
Expression of ??-synuclein in a human glioma cell line and its up-regulation by interleukin-1??
Tanji, K., Imaizumi, T., Yoshida, H., Mori, F., Yoshimoto, M., Satoh, K., & Wakabayashi, K. (2001) · Neuroreport · doi:10.1097/00001756-200107030-00028 · Cited by 81 · see citing works
Expression of α-synuclein in a human glioma cell line and its up-regulation by interleukin-1β
丹治, 邦. (2002) · Medical Entomology and Zoology · Cited by 11 · see citing works
Solano (2000) · doi:10.1002/1531-8249(200002)47:2 · Cited by 3 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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 · see citing works
Toll-Like Receptor 4 Promotes α-Synuclein Clearance and Survival of Nigral Dopaminergic Neurons
Stefanova, N., Fellner, L., Reindl, M., Masliah, E., Poewe, W., & Wenning, G. K. (2011) · The American Journal of Pathology · doi:10.1016/j.ajpath.2011.04.013 · Cited by 272 · see citing works
Shults, C. W., Rockenstein, E., Crews, L., Adame, A., Mante, M., Larrea, G., Hashimoto, M., Song, D., Iwatsubo, T., Tsuboi, K., et al. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.3527-05.2005 · Cited by 254 · see citing works
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 · see citing works
Self-citationAbsence of α-synuclein mRNA expression in normal and multiple system atrophy oligodendroglia
Miller, D. W., Johnson, J. M., Solano, S. M., Hollingsworth, Z. R., Standaert, D. G., & Young, A. B. (2005) · Journal of Neural Transmission · doi:10.1007/s00702-005-0378-1 · Cited by 198 · see citing works
Neuropathology of multiple system atrophy: New thoughts about pathogenesis
Jellinger, K. A. (2014) · Movement Disorders · doi:10.1002/mds.26052 · Cited by 181 · see citing works
Oligodendroglia and Myelin in Neurodegenerative Diseases: More Than Just Bystanders?
Ettle, B., Schlachetzki, J. C. M., & Winkler, J. (2016) · Molecular Neurobiology · doi:10.1007/s12035-015-9205-3 · Cited by 160 · see citing works
Nishie, M., Mori, F., Yoshimoto, M., Takahashi, H., & Wakabayashi, K. (2004) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2004.00564.x · Cited by 123 · see citing works
Stefanova, N., Georgievska, B., Eriksson, H., Poewe, W., & Wenning, G. K. (2012) · Neurotoxicity Research · doi:10.1007/s12640-011-9294-3 · Cited by 111 · see citing works
Altered lipid levels provide evidence for myelin dysfunction in multiple system atrophy
Don, A. S., Hsiao, J.-H. T., Bleasel, J. M., Couttas, T. A., Halliday, G. M., & Kim, W. S. (2014) · Acta Neuropathologica Communications · doi:10.1186/s40478-014-0150-6 · Cited by 88 · see citing works
Stemberger, S., Poewe, W., Wenning, G. K., & Stefanova, N. (2010) · Experimental Neurology · doi:10.1016/j.expneurol.2010.05.008 · Cited by 83 · see citing works
Oligodendroglial α‐synucleinopathy‐driven neuroinflammation in multiple system atrophy
Hoffmann, A., Ettle, B., Battis, K., Reiprich, S., Schlachetzki, J. C. M., Masliah, E., Wegner, M., Kuhlmann, T., Riemenschneider, M. J., & Winkler, J. (2019) · Brain Pathology · doi:10.1111/bpa.12678 · Cited by 83 · see citing works
Refolo, V., Bez, F., Polissidis, A., Kuzdas-Wood, D., Sturm, E., Kamaratou, M., Poewe, W., Stefanis, L., Angela Cenci, M., Romero-Ramos, M., et al. (2018) · Acta Neuropathologica Communications · doi:10.1186/s40478-017-0504-y · Cited by 67 · see citing works
Intracellular alpha-synuclein affects early maturation of primary oligodendrocyte progenitor cells
Ettle, B., Reiprich, S., Deusser, J., Schlachetzki, J. C. M., Xiang, W., Prots, I., Masliah, E., Winner, B., Wegner, M., & Winkler, J. (2014) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2014.06.012 · Cited by 57 · see citing works
Mandel, R. J., Marmion, D. J., Kirik, D., Chu, Y., Heindel, C., McCown, T., Gray, S. J., & Kordower, J. H. (2017) · Acta Neuropathologica Communications · doi:10.1186/s40478-017-0451-7 · Cited by 56 · see citing works
Fernagut, P. O., Meissner, W. G., Biran, M., Fantin, M., Bassil, F., Franconi, J. M., & Tison, F. (2014) · Synapse · doi:10.1002/syn.21719 · Cited by 35 · see citing works
Animal modeling an oligodendrogliopathy – multiple system atrophy
Bleasel, J. M., Halliday, G. M., & Kim, W. S. (2016) · Acta Neuropathologica Communications · doi:10.1186/s40478-016-0279-6 · Cited by 19 · see citing works
- Authors
- Kahle, P. J., Neumann, M., Ozmen, L., Müller, V., Jacobsen, H., Spooren, W., Fuss, B., Mallon, B., Macklin, W. B., Fujiwara, H., Hasegawa, M., Iwatsubo, T., Kretzschmar, H. A., & Haass, C.
- Affiliations
- Ludwig-Maximilians-Universität München (DE)
- F. Hoffmann-La Roche AG (CH)
- Cleveland Clinic (US)
- The University of Tokyo (JP)
- ORCID
- Venue
- The EMBO Reports
- Published
- 2002-06-01
- Volume
- 3
- Issue
- 6
- Pages
- 583-588
- ISSN
- 1469-221X (ISSN-L)
- 1469-3178
- PMC
- PMC1084143
- OpenAlex
- W2123133951
- Cited by
- 314
- References
- 30
- Citations by year
- 2026: 9 · 2025: 5 · 2024: 11 · 2023: 5 · 2022: 14 · 2021: 14 · 2020: 17 · 2019: 17 · 2018: 12 · 2017: 14 · 2016: 11 · 2015: 12 · 2014: 18 · 2013: 21 · 2012: 13
- FWCI
- 9.51
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- EMBO Reports (publishedVersion)
- PubMed Central (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (SFB 596)
- National Institute of Neurological Disorders and Stroke (R01NS025304)
- 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, multiple system atrophy, oligodendrocytes, glial cytoplasmic inclusions, hyperphosphorylation, S129 phosphorylation, transgenic mice, ectopic protein expression, protein aggregation
- MeSH terms
- Animals, Brain, Humans, Mice, Transgenic, Nerve Tissue Proteins, Oligodendroglia, Phosphorylation, Solubility, Microscopy, Confocal, Multiple System Atrophy, Mice, Synucleins, alpha-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
