The DOI matches its Crossref record; 85 of the 86 references it cites were found in a registry or an index.
Synuclein activates microglia in a model of Parkinson's disease
Open accessAbstract
Parkinson's disease (PD) is the most common neurodegenerative movement disorder afflicting >500,000 patients in the United States alone. This age-related progressive disorder is typified by invariant loss of dopaminergic substantia nigra neurons (DAN), dystrophic neurites, the presence of alpha-synuclein (SYN) positive intracytoplasmic inclusions (Lewy bodies) in the remaining DAN, and activated microglia. As such, microglial activation and resultant increase in proinflammatory molecules have moved to the forefront of PD research as a potential pathobiologic mechanism of disease. Herein, we present data demonstrating early microglial activation in mice that over-express wild-type SYN, the release of SYN from a SYN overexpressing MN9D cell line, and dose-dependent SYN-mediated activation of primary microglial cultures with consequent increases in proinflammatory molecules. Furthermore, we provide evidence that the CD36 scavenger receptor and downstream kinases are involved in SYN-mediated microglial activation. Together, our data suggest an early role for SYN and inflammation in PD pathogenesis.
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“SR-B2 promotes α-synuclein–microglial interactions64 and senses misfolded mutant or oxidized SOD1 in diseased motor neurons or in the extracellular space, rendering these cells proinflammatory85.”
From Microglia in neurodegeneration (2018) · cites this paper as [64]
In the citing paper
“Microglia accumulate near α-synuclein deposits and become proinflammatory in a manner dependent on receptors that also bind Aβ, such as CD36 and TLR263–65.”
From Microglia in neurodegeneration (2018) · cites this paper as [64]
In the citing paper
“Microglia also phagocytose α-synuclein, the constituent protein of Lewy bodies in Parkinson’s and Lewy Body dementias, and become pro-inflammatory in the process, expressing cytokines (IL1β, IL6, TNFα), reactive oxygen species (ROS) and prostaglandin synthesising cyclooxygenase 2 (COX2) [24,25,26].”
From ROS Generation in Microglia: Understanding Oxidative Stress and Inflammation in Neurodegenerative Disease (2020) · cites this paper as [25]
Citations
Cites
Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4
LAEMMLI, U. K. (1970) · Nature · doi:10.1038/227680a0 · Cited by 249,961
Raza, H., John, A., & Nemmar, A. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350087 · Cited by 47,311
Mutation 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
Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism
Kitada, T., Asakawa, S., Hattori, N., Matsumine, H., Yamamura, Y., Minoshima, S., Yokochi, M., Mizuno, Y., & Shimizu, N. (1998) · Nature · doi:10.1038/33416 · Cited by 5,227
Microglia: a sensor for pathological events in the CNS
Kreutzberg, G. W. (1996) · Trends in Neurosciences · doi:10.1016/0166-2236(96)10049-7 · Cited by 4,396
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
Microglia-mediated neurotoxicity: uncovering the molecular mechanisms
Block, M. L., Zecca, L., & Hong, J.-S. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2038 · Cited by 4,110
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
McGeer, P. L., Itagaki, S., Boyes, B. E., & McGeer, E. G. (1988) · Neurology · doi:10.1212/wnl.38.8.1285 · Cited by 2,990
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
Research works printed but not linked: 1
- Manning-Bog, 2001, The herbicide paraquat causes upregulation and aggregation of alpha-synuclein in mice, J. Biol. Chem., 13, 13
Cited by
Sorted by citations
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Immunity in Parkinson's disease – The role of innate responses
Iyengar, A. S., Dunkley, P. R., & Dickson, P. W. (2025) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2025.578716 · Cited by 4
Alpha-Synuclein and the Immune Response in Parkinson’s Disease
Roodveldt, C., Labrador‐Garrido, A., Izquierdo, G., & Pozo, D. (2011) · InTech eBooks · doi:10.5772/17417 · Cited by 3
“This illustrates how microglia itself, and not only dopaminergic neurons, can be highly affected by the medium in a PD scenario.”
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Wilshusen, R. A., & Mosley, R. L. (2014) · Springer eBooks · doi:10.1007/978-1-4939-1071-7_7 · Cited by 2
“Morphological changes of microglia become more macrophagelike in appearance, express surface proteins such as CD11b or major histocompatibility complex (MHC) antigens, and change the expression pattern of cytokines to resemble a more proinfl ammatory profi le [ 38 , 52 , 53 ].”
BackgroundPérez, T. S., & Gil, Y. B. (2017) · Revista de Indias · doi:10.3989/revindias.2017.009 · Cited by 2
Role of the Innate and Adaptive Immune System in the Pathogenesis of PD
Kannarkat, G. T., & Tansey, M. G. (2014) · Springer eBooks · doi:10.1007/978-3-319-08046-8_3 · Cited by 2
Kline, E. M., Jernigan, J. E., Scharer, C. D., Maurer, J., Hicks, S. L., Herrick, M. K., Wallings, R. L., Kelly, S. D., Chang, J., Menees, K. B., et al. (2025) · Scientific Reports · doi:10.1038/s41598-025-95679-3 · Cited by 1
Wang, Y.-C., Huang, L.-Y., Yan-Fu, Xiong, S.-Y., Wang, Z.-T., Tan, C., & Tan, L. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-025-06729-3 · Cited by 1
Parkinson's disease: A chronic systemic inflammatory disorder
Khan, H., & Benskey, M. J. (2025) · Handbook of behavioral neuroscience · doi:10.1016/b978-0-443-21992-4.00006-3 · Cited by 1
van der Heide, A., Kischkel, B., Bleeker‐Rovers, C. P., de Jonge, M. I., Bloem, B. R., Verbeek, M. M., Joosten, L. A. B., & Helmich, R. C. G. (2025) · npj Parkinson s Disease · doi:10.1038/s41531-025-01178-7 · Cited by 2
“Pathological α -synuclein and neurotransmitter imbalances in PD can trigger the activation of microglia and astrocytes 9,10 , leading to neuroin fl ammation characterized by elevatedconcentrationsofC-reactiveprotein(CRP),reactiveoxygenspecies (ROS) 11,12 and pro-in fl ammatory cytokines 6,8,13 .”
Dapueto, A., Olivera‐Bravo, S., & Prunell, G. (2026) · Neuroglia · doi:10.3390/neuroglia7010005 · Cited by 1
“Moreover, preclinical models of the disease demonstrate that robust immune activation can precede dopaminergic neuron degeneration in the SNpc [27–30], and direct injection of lipopolysaccharide, a potent proinflammatory stimulus, into the SNpc is sufficient to trigger dopaminergic neuron loss [31].”
Weber, H., Statz, M., Casadei, N., Rieß, O., Richter, F., Hermann, W., Storch, A., & Fauser, M. (2026) · npj Parkinson s Disease · doi:10.1038/s41531-026-01436-2 · Cited by 1
“Also, enhanced system-wide neuroin fl ammation has previously been reported in the SNCA rat model 68 , and it is well established that α -synuclein accumulation can trigger microglial activation in vivo and in vitro 69 – 71 .”
Hyun, M., & Lee, S. (2009) · Experimental Neurobiology · doi:10.5607/en.2009.18.1.19 · Cited by 1
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Romero‐Ramos, M. (2017) · Springer eBooks · doi:10.1007/978-3-319-64597-1_150-1 · Cited by 1
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Blake, S. M., Piboolnurak, P., Borman, P. L., Harding, T., & Blake, C. P. (2022) · GSC Biological and Pharmaceutical Sciences · doi:10.30574/gscbps.2022.18.2.0052 · Cited by 1
James, B. C., Cox, A. J., & Lewohl, J. M. (2024) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.15340 · Cited by 1
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Ciolac, D., & González‐Escamilla, G. (2024) · Neuromethods · doi:10.1007/978-1-0716-4083-8_4 · Cited by 1
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Cho, S., & Febbraio, M. (2013) · Springer eBooks · doi:10.1007/978-1-4614-8915-3_18 · Cited by 1
Immune response during idiopathic Parkinson's disease: From humans to animal models
Nissen, S. K., Ferreira, S. A., Klæstrup, I. H., & Romero‐Ramos, M. (2021) · International review of movement disorders · doi:10.1016/bs.irmvd.2021.08.006 · Cited by 1
Pabon, M. M. (2011) · Digital Commons - University of South Florida (University of South Florida) · Cited by 1
Modulation of the ROCK pathway in models of Parkinson´s disease
Saal, K. A. (2015) · doi:10.53846/goediss-5423 · Cited by 1
Alpha-synuclein and the multiple hit hypothesis of Parkinson's disease
Feng, L. (2012) · DigitalGeorgetown (Georgetown University Library) · Cited by 1
Environmental Explorations of Parkinson's Disease Using Rodent Genetic Models
Chesselet, M., & Fernagut, P. (2008) · Elsevier eBooks · doi:10.1016/b978-0-12-374028-1.00021-x · Cited by 1
Iba, M., McDevitt, R. A., Kim, C., Roy, R., Sarantopoulou, D., Tommer, E., Kwon, S., Siegars, B., Sallin, M. A., Sen, J. M., et al. (2021) · Research Square · doi:10.21203/rs.3.rs-211252/v1 · Cited by 1
Microglial properties in health and disease
Krabbe, G. (2011) · Universitätsbibliothek der FU Berlin Hochschulschriftenstelle u. Dokumentenserver · doi:10.17169/refubium-15999
Effects of Alpha-Synuclein on Cellular Homeostasis
Vekrellis, K., Minakaki, G., & Emmanouilidou, E. (2011) · InTech eBooks · doi:10.5772/17637
“microglia activation which induces the production of various cytokines, such as IL1β and IL6, and inflammation-related enzymes (Su et al., 2008; Zhang et al., 2005).”
BackgroundWakabayashi, K. (2010) · Elsevier eBooks · doi:10.1016/b978-0-12-374105-9.00247-1
Bennett, N. K. (2016) · doi:10.7282/t3sf2zgb
“A considerable body of work indicates that intercellularly transmitted ASYN from neuron-to-glia triggers microglial activation [70, 73-76], and chronic and excessive ASYN exposure has been observed to result in microglial secretion of neurotoxic substances including reactive oxygen species [77].”
BackgroundInfluentialParkinson’s Disease and Other Synucleinopathies
Cookson, M. R. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-811304-2.00006-7
Vezheeva, O. A., Sergeeva, T. N., & Sergeev, V. G. (2013) · Medical academic journal · doi:10.17816/maj13371-77
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Locke, S. K. (1997)
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Belova, O. V., Arefieva, T. I., & Moskvina, S. N. (2020) · Neuroscience and Behavioral Physiology · doi:10.1007/s11055-020-01014-w
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Hanamsagar, R., Cardona, S. M., Kielian, T., & Cardona, A. E. (2014) · Springer eBooks · doi:10.1007/978-1-4939-1429-6_5
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Romero‐Ramos, M. (2019) · Springer eBooks · doi:10.1007/978-3-319-99375-1_150
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Rady, A. H. A., Hendi, N. I., Hefnawy, M. T., Hassan, H., Hammad, G., ALsaad, S. A., & Meshref, M. M. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-15702-8.00021-x
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Paquette, C., Charlton, T., Prowse, N. A., Fortin, T., Hongyu, S., & Hayley, S. P. (2025) · SSRN Electronic Journal · doi:10.2139/ssrn.5370764
Jin, T., Shi, R.-Z., Shi, J.-W., Liu, F., & Liang, Y. (2025) · Journal of Asian Natural Products Research · doi:10.1080/10286020.2025.2544148
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Szklany, K. (2013) · Utrecht University Repository (Utrecht University)
Zhang, Y.-N., Fan, J.-K., Gu, L., Yang, H.-M., Zhan, S.-Q., & Zhang, H. (2021) · Figshare · doi:10.6084/m9.figshare.13605718
Zhang, Y.-N., Fan, J.-K., Gu, L., Yang, H.-M., Zhan, S.-Q., & Zhang, H. (2021) · Figshare · doi:10.6084/m9.figshare.13605715
Beal, M. F., Chiluwal, J., Calingasan, N. Y., Milne, G. L., Shchepinov, M. S., & Tapias, V. (2020) · Figshare · doi:10.6084/m9.figshare.13467573
Iba, M., McDevitt, R. A., Kim, C., Roy, R., Sarantopoulou, D., Tommer, E., Siegars, B., Sallin, M. A., Kwon, S., Sen, J. M., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20967836
Zhang, Y.-N., Fan, J.-K., Gu, L., Yang, H.-M., Zhan, S., & Zhang, H. (2021) · Figshare · doi:10.6084/m9.figshare.13605712
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“This is consistent with a previous study that showed that α -syn dose-dependently increased the fraction of activated primary microglial mono-culture with a “ fried egg ” appearance [45].”
Hoffmann, P. A., Martin, J. C., Evora, A., Brillet, F., Scott, K. P., & Platt, B. (2026) · Research Square · doi:10.21203/rs.3.rs-8852210/v1
Understanding the role of perivascular macrophages in Parkinson's disease pathophysiology
Fuentealba, J. R. (2017) · theses.fr (ABES) · doi:10.70675/b2e8f905z4f72z497eza017zc5b9d7fe53a1
“Also, nitrated, misfolded or aggregated forms of ⍺-Syn can activate microglial TLR4, leading to proliferation (Béraud and Maguire-Zeiss, 2012; Reynolds et al., 2008; Su et al., 2008; Zhang et al., 2005).”
BackgroundÉtude des bases cérébrales de la maladie à corps de Lewy par IRM multimodale
Chabran, E. (2019) · theses.fr (ABES) · doi:10.70675/0e043513z1fabz4531za279z1f82876b9864
“…sécrétée provoque une suractivation des cellules microgliales, qui déclenchent des cascades pro-inflammatoires aboutissant en dernier lieu à un effet neurotoxique (notamment du fait de la production de radicaux libres et de cytokines) [Zhang et al., 2005; Su et al., 2008; Hoenen et al., 2016].”
BackgroundModélisation et recherche de stratégies expérimentales dans l’atrophie multisystématisée
Guerin, P. A. (2018) · theses.fr (ABES) · doi:10.70675/b4a315bfz31baz46d1z9e9fz88481e022180
Étude moléculaire de l'inflammation chronique dans la maladie de Parkinson
Compagnion, A. (2019) · theses.fr (ABES) · doi:10.70675/04ca138dz3131z4e24z884czbba2f7954a99
Yildirim-Balatan, C. (2021) · theses.fr (ABES) · doi:10.70675/3372ff2ez69a6z4970z881bze4dfe0a15571
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Patrigeon, M. (2022) · theses.fr (ABES) · doi:10.70675/8d75463az5b67z46bfz8649zc3e016dabdda
Hoffmann, P. A., Martin, J. C., Evora, A., Brillet, F., Scott, K. P., & Platt, B. (2026) · Research Square · doi:10.21203/rs.3.rs-10729381/v1
Gaur, P. K., Bisht, P. R., & Gupta, S. L. (2026) · Journal of Biomaterials Science Polymer Edition · doi:10.1080/09205063.2026.2723464
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Toutounchian, S., & Kiani, I. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-40467-2.00004-x
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Лазаревна, А. Е., Idova, G. V., Zhanaeva, S. Y., Tikhonova, M. A., Gevorgyan, M. M., & Aftanas, L. I. (2026) · Biochemistry (Moscow) · doi:10.1134/s0006297926600614
“Aggregated α-synuclein is known to activate microglia and promote the production of pro-inflammatory cytokines both in vitro and in vivo [29, 30].”
Groenewald, K., Klein, J. C., Fryer, T. D., Smith, G., Dzamko, N., Chua, M., Scott, A. M., Baskar, J., Hamprecht, D. W., Everett, J., et al. (2026) · Frontiers in Neurology · doi:10.3389/fneur.2026.1951452
Metadata
- Authors
- Su, X., Maguire-Zeiss, K. A., Giuliano, R., Prifti, L., Venkatesh, K., & Federoff, H. J.
- Affiliations
- University of Rochester Medicine (US)
- Corresponding author
- Federoff, Howard J.
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2008-11
- Volume
- 29
- Issue
- 11
- Pages
- 1690-1701
- ISSN
- 0197-4580 (ISSN-L)
- PMC
- PMC2621109
- OpenAlex
- W2120997873
- Cited by
- 474
- References
- 86
- Citations by year
- 2026: 11 · 2025: 17 · 2024: 27 · 2023: 19 · 2022: 46 · 2021: 46 · 2020: 37 · 2019: 30 · 2018: 26 · 2017: 18 · 2016: 15 · 2015: 22 · 2014: 32 · 2013: 21 · 2012: 24
- FWCI
- 12.04
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (T32NS007489)
- 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
- Parkinson's disease, alpha-synuclein, microglial activation, neuroinflammation, CD36 scavenger receptor, proinflammatory molecules, Lewy bodies, MN9D cells, pathogenesis
- MeSH terms
- Animals, Cell Line, Disease Models, Animal, Humans, Male, Mice, Inbred C57BL, Mice, Transgenic, Cytokines, Microglia, Parkinsonian Disorders, Mice, Synucleins
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