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.
Integrity signals
Registry
Cites
Statistics
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?
SR-B2 promotes α-synuclein-microglial interactions and detects misfolded mutant or oxidized SOD1 in diseased motor neurons or extracellular space, making these cells proinflammatory.
“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]
Microglia accumulate near α-synuclein deposits and become proinflammatory via receptors that also bind Aβ, such as CD36 and TLR2.
“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]
Microglia phagocytose α-synuclein and become pro-inflammatory, expressing cytokines (IL1β, IL6, TNFα), ROS and COX2.
“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]
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 · see citing works
Raza, H., John, A., & Nemmar, A. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350087 · Cited by 47,311 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 3,151 · see citing works
McGeer, P. L., Itagaki, S., Boyes, B. E., & McGeer, E. G. (1988) · Neurology · doi:10.1212/wnl.38.8.1285 · Cited by 2,990 · see citing works
Masliah, E., Rockenstein, E. M., Veinbergs, I., Mallory, M. E., Hashimoto, M., Takeda, A., Sagara, Y., Sisk, A., & Mucke, L. (2000) · Science · doi:10.1126/science.287.5456.1265 · Cited by 1,763 · see citing works
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 · see citing works
(1998) · Europe PMC (PubMed Central) · Cited by 1,594 · see citing works
Zhang, W., Wang, T., Pei, Z., Miller, D. S., Wu, X., Block, M. L., Wilson, B., Zhang, W., Zhou, Y., Hong, J.-S., et al. (2005) · The FASEB Journal · doi:10.1096/fj.04-2751com · Cited by 1,265 · see citing works
Liu, B., & Hong, J.-S. (2003) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.102.035048 · Cited by 1,095 · see citing works
Lee, M. K., Stirling, W., Xu, Y., Xu, X., Qui, D., Mandir, A. S., Dawson, T. M., Copeland, N. G., Jenkins, N. A., & Price, D. L. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.132197599 · Cited by 824 · see citing works
Intravesicular Localization and Exocytosis of α-Synuclein and its Aggregates
Lee, H.-J., Patel, S. S., & Lee, S. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.0692-05.2005 · Cited by 798 · see citing works
Mapping of a gene for Parkinson's disease to chromosome 4q21-q23
Polymeropoulos, M. H., Higgins, J. J., Golbe, L. I., Johnson, W. G., Ide, S. E., Di Iorio, G., Sanges, G., Stenroos, E. S., Pho, L. T., Schaffer, A. A., et al. (1996) · Science · doi:10.1126/science.274.5290.1197 · Cited by 788 · see citing works
Fiber 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 748 · see citing works
The Herbicide Paraquat Causes Up-regulation and Aggregation of α-Synuclein in Mice
Manning-Bog, A., McCormack, A. L., Li, J., Uversky, V. N., Fink, A. L., & Monte, D. A. D. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.c100560200 · Cited by 684 · see citing works
Kim, Y. S., & Joh, T. H. (2006) · Experimental & Molecular Medicine · doi:10.1038/emm.2006.40 · Cited by 655 · see citing works
Kahle, 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
Experimental models of Parkinson's disease
Beal, M. F. (2001) · Nature reviews. Neuroscience · doi:10.1038/35072550 · Cited by 634 · see citing works
El-Agnaf, O. M. A., Salem, S. A., Paleologou, K. E., Cooper, L. J., Fullwood, N. J., Gibson, M. J., Curran, M. D., Court, J. A., Mann, D. M. A., Ikeda, S.-I., et al. (2003) · The FASEB Journal · doi:10.1096/fj.03-0098fje · Cited by 590 · see citing works
Abbas, N., Lücking, C. B., Ricard, S., Dürr, A., Bonifati, V., Michele, G. D., Bouley, S., Vaughan, J. R., Gasser, T., Marconi, R., et al. (1999) · Human Molecular Genetics · doi:10.1093/hmg/8.4.567 · Cited by 529 · see citing works
Inflammation and the Degenerative Diseases of Aging
McGeer, P. L., & McGeer, E. G. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1332.007 · Cited by 519 · see citing works
Przedborski, S., Jackson-Lewis, V. R., Naini, A., Jakowec, M. W., Petzinger, G. M., Miller, R., & Akram, M. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00183.x · Cited by 507 · see citing works
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 505 · see citing works
Neuropathology in mice expressing human alpha-synuclein
van der Putten, H., Wiederhold, K., Probst, A., Barbieri, S., Mistl, C., Danner, S., Kauffmann, S., Hofele, K., Spooren, W. P. J. M., Rüegg, M. A., et al. (2000) · PubMed Central · doi:10.5451/unibas-ep2767 · Cited by 505 · see citing works
Inflammatory Regulators in Parkinson's Disease: iNOS, Lipocortin-1, and Cyclooxygenases-1 and -2
Knott, C., Stern, G., & Wilkin, G. P. (2000) · Molecular and Cellular Neuroscience · doi:10.1006/mcne.2000.0914 · Cited by 503 · see citing works
A Cell Surface Receptor Complex for Fibrillar β-Amyloid Mediates Microglial Activation
Bamberger, M. E., Harris, M. E., McDonald, D. R., Husemann, J., & Landreth, G. E. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-07-02665.2003 · Cited by 501 · see citing works
CD36 Mediates the Innate Host Response to β-Amyloid
El Khoury, J. B., Moore, K. J., Means, T. K., Leung, J., Terada, K., Toft, M., Freeman, M. W., & Luster, A. D. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20021546 · Cited by 483 · see citing works
Neuropathology in Mice Expressing Human α-Synuclein
van der Putten, H., Wiederhold, K., Probst, A., Barbieri, S., Mistl, C., Danner, S., Kauffmann, S., Hofele, K., Spooren, W. P. J. M., Rüegg, M. A., et al. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-16-06021.2000 · Cited by 478 · see citing works
Tatton, N. A., & Kish, S. J. (1997) · Neuroscience · doi:10.1016/s0306-4522(96)00545-3 · Cited by 469 · see citing works
Langston, J. W., Irwin, I., Langston, E. B., & Forno, L. S. (1984) · Neuroscience Letters · doi:10.1016/0304-3940(84)90293-3 · Cited by 435 · see citing works
Croisier, E., Moran, L. B., Dexter, D. T., Pearce, R. K., & Graeber, M. B. (2005) · Journal of Neuroinflammation · doi:10.1186/1742-2094-2-14 · Cited by 414 · see citing works
Coraci, I. S., Husemann, J., Berman, J. W., Hulette, C., Dufour, J. H., Campanella, G. K., Luster, A. D., Silverstein, S. C., & El Khoury, J. B. (2002) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64354-4 · Cited by 398 · see citing works
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 · see citing works
Vila, M., Vukosavić, S., Jackson-Lewis, V. R., Neystat, M., Jakowec, M. W., & Przedborski, S. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.740721.x · Cited by 388 · see citing works
Borghi, R., Marchese, R., Negro, A., Marinelli, L., Forloni, G., Zaccheo, D., Abbruzzese, G., & Tabaton, M. (2000) · Neuroscience Letters · doi:10.1016/s0304-3940(00)01153-8 · Cited by 363 · see citing works
Husemann, J., Loike, J. D., Anankov, R., Febbraio, M., & Silverstein, S. C. (2002) · Glia · doi:10.1002/glia.10148 · Cited by 359 · see citing works
A CD36-initiated Signaling Cascade Mediates Inflammatory Effects of β-Amyloid
Moore, K. J., El Khoury, J., Medeiros, L. A., Terada, K., Geula, C., Luster, A. D., & Freeman, M. W. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m208788200 · Cited by 327 · see citing works
Thomas, D. M., Walker, P. D., Benjamins, J. A., Geddes, T. J., & Kuhn, D. M. (2004) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.104.070961 · Cited by 315 · see citing works
Neuroinflammatory processes in Parkinson's disease
Hirsch, É. C., Hunot, S., & Hartmann, A. (2005) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2004.10.013 · Cited by 298 · see citing works
Song, D. D., Shults, C. W., Sisk, A., Rockenstein, E. M., & Masliah, E. (2003) · Experimental Neurology · doi:10.1016/s0014-4886(03)00342-x · Cited by 294 · see citing works
MPTP induces alpha-synuclein aggregation in the substantia nigra of baboons
Kowall, N. W., Hantraye, P., Brouillet, E., Beal, M. F., McKee, A. C., & Ferrante, R. J. (2000) · Neuroreport · doi:10.1097/00001756-200001170-00041 · Cited by 291 · see citing works
Neurochemical findings in the MPTP model of Parkinson's disease
Schmidt, N., & Ferger, B. (2001) · Journal of Neural Transmission · doi:10.1007/s007020100004 · Cited by 290 · see citing works
Behavioral and Neurochemical Effects of Wild-Type and Mutated Human α-Synuclein in Transgenic Mice
Richfield, E. K., Thiruchelvam, M. J., Cory-Slechta, D. A., Wuertzer, C., Gainetdinov, R. R., Caron, M. G., Di Monte, D. A., & Federoff, H. J. (2002) · Experimental Neurology · doi:10.1006/exnr.2002.7882 · Cited by 285 · see citing works
Self-citationKohutnicka, M., Lewandowska, E., Kurkowska‐Jastrzębska, I., Członkowski, A., & Członkowska, A. (1998) · Immunopharmacology · doi:10.1016/s0162-3109(98)00022-8 · Cited by 283 · see citing works
Matsuoka, Y., Vila, M., Lincoln, S., McCormack, A., Picciano, M., LaFrancois, J., Yu, X., Dickson, D., Langston, W. J., McGowan, E., et al. (2001) · Neurobiology of Disease · doi:10.1006/nbdi.2001.0392 · Cited by 281 · see citing works
Familial Aggregation of Parkinson's Disease in Iceland
Sveinbjörnsdóttir, S., Hicks, A. A., Jónsson, T., Pétursson, H., Guðmundsson, G., Frigge, M. L., Kong, A., Gulcher, J. R., & Stefánsson, K. (2000) · New England Journal of Medicine · doi:10.1056/nejm200012143432404 · Cited by 275 · see citing works
Neural Activity Controls the Synaptic Accumulation of α-Synuclein
Fortin, D. L., Nemani, V. M., Voglmaier, S. M., Anthony, M. D., Ryan, T. A., & Edwards, R. H. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.2922-05.2005 · Cited by 271 · see citing works
MPTP-induced parkinsonism in human and non-human primates--clinical and experimental aspects.
Langston, J. W., Langston, E. B., & Irwin, I. (1984) · PubMed · Cited by 252 · see citing works
Proteolytic Cleavage of Extracellular Secreted α-Synuclein via Matrix Metalloproteinases
Sung, J. Y., Park, S., Lee, C.-H., Um, J. W., Lee, H. J., Kim, J., Oh, Y. J., Lee, S., Paik, S. R., & Chung, K. C. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m503341200 · Cited by 238 · see citing works
α-Synuclein activates stress signaling protein kinases in THP-1 cells and microglia
Klegeris, A., Pelech, S., Giasson, B. I., Maguire, J., Zhang, H., McGeer, E. G., & McGeer, P. L. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2006.11.013 · Cited by 227 · see citing works
Mechanisms of Cell Signaling and Inflammation in Alzheimers Disease
Ho, G. J., Drego, R., Hakimian, E., & Masliah, E. (2005) · Current Drug Targets - Inflammation & Allergy · doi:10.2174/1568010053586237 · Cited by 199 · see citing works
Expression of mutant alpha-synuclein causes increased susceptibility to dopamine toxicity
Tabrizi, S. J. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.18.2683 · Cited by 197 · see citing works
Przedborski, S., Chen, Q., Vila, M., Giasson, B. I., Djaldatti, R., Vukosavić, S., Souza, J. M., Jackson-Lewis, V. R., Lee, V. M. ‐., & Ischiropoulos, H. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00174.x · Cited by 190 · see citing works
Risk factors for dopaminergic neuron loss in human α‐synuclein transgenic mice
Thiruchelvam, M. J., Powers, J. M., Cory‐Slechta, D. A., & Richfield, E. K. (2004) · European Journal of Neuroscience · doi:10.1111/j.0953-816x.2004.03139.x · Cited by 174 · see citing works
Inflammation, the complement system and the diseases of aging
McGeer, E. G., Klegeris, A., & McGeer, P. L. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.08.008 · Cited by 170 · see citing works
Inflammation, Neurodegenerative Diseases, and Environmental Exposures
Campbell, A. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1332.008 · Cited by 163 · see citing works
Dose-dependent destruction of the coeruleus-cortical and nigral-striatal projections by MPTP
Seniuk, N. A., Tatton, W. G., & Greenwood, C. E. (1990) · Brain Research · doi:10.1016/0006-8993(90)91055-l · Cited by 153 · see citing works
Age-related susceptibility to MPTP-induced neurotoxicity in mice.
Ali, S. F., David, S. N., & Newport, G. D. (1993) · PubMed · Cited by 153 · see citing works
Gómez-Santos, C., Ferrer, I., Reiriz, J., Viñals, F., Barrachina, M., & Ambrosio, S. (2002) · Brain Research · doi:10.1016/s0006-8993(02)02422-8 · Cited by 148 · see citing works
The effect of fetal mesencephalon implants on primate MPTP-induced parkinsonism
Bankiewicz, K. S., Plunkett, R. J., Jacobowitz, D. M., Porrino, L. J., di Porzio, U., London, W. T., Kopin, I. J., & Oldfield, E. H. (1990) · Journal of neurosurgery · doi:10.3171/jns.1990.72.2.0231 · Cited by 142 · see citing works
Fibrillar Amyloid Protein Present in Atheroma Activates CD36 Signal Transduction
Medeiros, L. A., Khan, T., Khoury, J. B. E., Pham, C. L. L., Hatters, D. M., Howlett, G. J., Lopez, R., O’Brien, K. D., & Moore, K. J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m311735200 · Cited by 140 · see citing works
Strathdee, C., McLeod, M. R., & Hall, J. R. (1999) · Gene · doi:10.1016/s0378-1119(99)00045-1 · Cited by 138 · see citing works
Alpha synuclein is present in Lewy bodies in sporadic Parkinson's disease
Mezey, É., Dehejia, A. M., Harta, G., Suchy, S. F., Nussbaum, R. L., Brownstein, M. J., & Polymeropoulos, M. H. (1998) · Molecular Psychiatry · doi:10.1038/sj.mp.4000446 · Cited by 137 · see citing works
Rathke‐Hartlieb, S., Kahle, P. J., Neumann, M., Ozmen, L., Haid, S., Okochi, M., Haass, C., & Schulz, J. B. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00366.x · Cited by 128 · see citing works
Husemann, J., Loike, J. D., Kodama, T., & Silverstein, S. C. (2001) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(01)00239-9 · Cited by 123 · see citing works
Varastet, M., RICHE, D., Mazière, M., & Hantraye, P. (1994) · Neuroscience · doi:10.1016/0306-4522(94)90006-x · Cited by 118 · see citing works
Microglial cells respond to amyloidogenic PrP peptide by the production of inflammatory cytokines
Peyrin, J., Lasmézas, C. I., Haı̈k, S., Tagliavini, F., Salmona, M., Williams, A., Richie, D., Deslys, J., & Dormont, D. (1999) · Neuroreport · doi:10.1097/00001756-199903170-00012 · Cited by 115 · see citing works
Binding Sites of Amyloid β-Peptide in Cell Plasma Membrane and Implications for Alzheimers Disease
Verdier, Y., & Penke, B. (2004) · Current Protein and Peptide Science · doi:10.2174/1389203043486937 · Cited by 114 · see citing works
Ancolio, K., da Costa, C. A., Uéda, K., & Checler, F. (2000) · Neuroscience Letters · doi:10.1016/s0304-3940(00)01049-1 · Cited by 110 · see citing works
Transgenic Models of α‐Synuclein Pathology
Hashimoto, M., Rockenstein, E. M., & Masliah, E. (2003) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2003.tb07475.x · Cited by 108 · see citing works
Miller, R. M., Callahan, L. M., Casaceli, C., Chen, L., Kiser, G. L., Chui, B., Kaysser-Kranich, T., Sendera, T. J., Palaniappan, C., & Federoff, H. J. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.4204-03.2004 · Cited by 104 · see citing works
Self-citationGenetics of Parkinson's Disease
Polymeropoulos, M. H. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb06901.x · Cited by 63 · see citing works
Convergent Pathobiologic Model of Parkinson's Disease
Maguire‐Zeiss, K. A., & Federoff, H. J. (2003) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2003.tb07473.x · Cited by 58 · see citing works
Self-citationDong, Z., Ferger, B., Feldon, J., & Büeler, H. (2002) · Journal of Neurobiology · doi:10.1002/neu.10094 · Cited by 47 · see citing works
Kunjathoor, V. V., Tseng, A. A., Medeiros, L. A., Khan, T., & Moore, K. J. (2004) · Journal of Neuroinflammation · doi:10.1186/1742-2094-1-23 · Cited by 44 · see citing works
Progress in the clinical and molecular genetics of familial parkinsonism
Kitada, T., Asakawa, S., Matsumine, H., Hattori, N., Shimura, H., Minoshima, S., Shimizu, N., & Mizuno, Y. (2000) · Neurogenetics · doi:10.1007/s100489900083 · Cited by 41 · see citing works
Identification of human α-synuclein specific single chain antibodies
Maguire‐Zeiss, K. A., Wang, C. I., Yehling, E., Sullivan, M. A., Short, D. W., Su, X., Gouzer, G., Henricksen, L. A., Wuertzer, C. A., & Federoff, H. J. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.08.127 · Cited by 32 · see citing works
Self-citationHeller, A., Price, S. D., & Won, L. (1996) · Brain Research · doi:10.1016/0006-8993(96)00345-9 · Cited by 29 · see citing works
Overview of Parkinson's Disease
Duvoisin, R. C. (1992) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1992.tb24537.x · Cited by 28 · see citing works
Heller, A., Freeney, A., Hessefort, S., Villereal, M. L., & Won, L. (2000) · Neuroscience Letters · doi:10.1016/s0304-3940(00)01589-5 · Cited by 6 · see citing works
Flagged first, then by citations
1 of the 86 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Neuroinflammation in Parkinson’s disease: A target for neuroprotection?
Hirsch, E. C., & Hunot, S. (2009) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70062-6 · Cited by 1,984 · see citing works
The Role of Oxidative Stress in Parkinson's Disease
Dias, V., Junn, E., & Mouradian, M. M. (2013) · Journal of Parkinson’s Disease · doi:10.3233/jpd-130230 · Cited by 1,845 · see citing works
“Similarly, exposure of primary microglial cells to recombinant aggregated or mutated alphasynuclein results in increased activated microglia and ROS production followed by the secretion of TNF-alpha, IL6 and IL-1beta [266] [272] [273] and the activation of intracellular pathways such as ERK1/2 and p38 MAPK [272].”
BackgroundMicroglia in neurodegeneration
Hickman, S., Izzy, S., Sen, P., Morsett, L., & El Khoury, J. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0242-x · Cited by 1,710 · see citing works
Role of Pro-Inflammatory Cytokines Released from Microglia in Neurodegenerative Diseases
Smith, J. A., Das, A., Ray, S. K., & Banik, N. L. (2012) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2011.10.004 · Cited by 1,165 · see citing works
Emmanouilidou, E., Melachroinou, K., Roumeliotis, T., Garbis, S. D., Ntzouni, M., Margaritis, L. H., Stefanis, L., & Vekrellis, K. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.5699-09.2010 · Cited by 1,115 · see citing works
“It has been reported that recombinant -synuclein can activate microglia cells (Zhang et al., 2005; Su et al., 2008).”
BackgroundSimpson, D. S. A., & Oliver, P. L. (2020) · Antioxidants · doi:10.3390/antiox9080743 · Cited by 1,044 · see citing works
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 · see citing works
Neuroinflammation in Parkinson's disease and its potential as therapeutic target
Wang, Q., Liu, Y., & Zhou, J. (2015) · Translational Neurodegeneration · doi:10.1186/s40035-015-0042-0 · Cited by 884 · see citing works
“Wild-type or pathogenic forms of α-synuclein induces pronounced microglial activation in vitro [63].”
BackgroundKim, C., Ho, D.-H., Suk, J.-E., You, S., Michael, S., Kang, J., Joong Lee, S., Masliah, E., Hwang, D., Lee, H.-J., et al. (2013) · Nature Communications · doi:10.1038/ncomms2534 · Cited by 856 · see citing works
Inflammation in Parkinson’s Disease: Mechanisms and Therapeutic Implications
Pajares, M., I. Rojo, A., Manda, G., Boscá, L., & Cuadrado, A. (2020) · Cells · doi:10.3390/cells9071687 · Cited by 779 · see citing works
Alpha-synuclein: Pathology, mitochondrial dysfunction and neuroinflammation in Parkinson’s disease
Rocha, E. M., Miranda, B. D., & Sanders, L. H. (2017) · Neurobiology of Disease · doi:10.1016/j.nbd.2017.04.004 · Cited by 769 · see citing works
Microglia: biology and pathology
Graeber, M. B., & Streit, W. J. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0622-0 · Cited by 720 · see citing works
“In keeping with the view that microglia in PD are reactive rather than aggressive, synuclein has been found to stimulate microglia [174].”
BackgroundMicroglia in Neurological Diseases: A Road Map to Brain-Disease Dependent-Inflammatory Response
Bachiller, S., Jiménez-Ferrer, I., Paulus, A., Yang, Y., Swanberg, M., Deierborg, T., & Boza‐Serrano, A. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00488 · Cited by 706 · see citing works
Toll‐like receptor 4 is required for α‐synuclein dependent activation of microglia and astroglia
Fellner, L., Irschick, R., Schanda, K., Reindl, M., Klimaschewski, L., Poewe, W., Wenning, G. K., & Stefanova, N. (2013) · Glia · doi:10.1002/glia.22437 · Cited by 697 · see citing works
“VC 2012 Wiley Periodicals, Inc. Reynolds et al., 2008; Rojanathammanee et al., 2011; Su et al., 2008).”
BackgroundTakata, F., Nakagawa, S., Matsumoto, J., & Dohgu, S. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.661838 · Cited by 651 · see citing works
Neuroinflammation in Parkinson's disease
Hirsch, É. C., Vyas, S., & Hunot, S. (2011) · Parkinsonism & Related Disorders · doi:10.1016/s1353-8020(11)70065-7 · Cited by 642 · see citing works
“This hypothesis is supported by several lines of evidence: (1) Overexpression of a-synuclein in animals leads to neuroinflammatory processes [14].”
ResultJiang, T., Sun, Q., & Chen, S. (2016) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2016.07.005 · Cited by 594 · see citing works
“Microglial cells are a dynamic immune cell population of the CNS. Evidence suggested that extracellular aggregated α-Syn activated microglia specifically (Su et al., 2008; Zhang et al., 2007).”
BackgroundTansey, M. G., McCoy, M. K., & Frank-Cannon, T. C. (2007) · Experimental Neurology · doi:10.1016/j.expneurol.2007.07.004 · Cited by 580 · see citing works
“…that mice that overexpress wild-type α-synuclein display early microglia activation and that α-synuclein release from an α-synuclein-overexpressing dopaminergic neuron-like cell line triggers a cascade of proinflammatory mediators that include TNF, IL-1β, IL-6, COX-2 and iNOS (Su et al., 2007).”
BackgroundInfluentialMicroglia in Neuroinflammation and Neurodegeneration: From Understanding to Therapy
Muzio, L., Viotti, A., & Martino, G. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.742065 · Cited by 581 · see citing works
“Peripheral T cells can infiltrate the CNS of PD patients (Brochard et al., 2009), and interact with the α-synuclein protein, stimulating microglial activation – i.e., increase of MHC II levels – and eventually concurring to the demise of DA neurons as shown in a rat model (Subbarayan et al., 2020).”
BackgroundParkinson’s Disease: Etiology, Neuropathology, and Pathogenesis
Kouli, A., Torsney, K., & Kuan, W. (2018) · Codon Publications eBooks · doi:10.15586/codonpublications.parkinsonsdisease.2018.ch1 · Cited by 556 · see citing works
“For instance, in primary cultures, α-synuclein mediates a dose-dependent activation of microglia (154).”
Microbiome–microglia connections via the gut–brain axis
Abdel-Haq, R., Schlachetzki, J. C. M., Glass, C. K., & Mazmanian, S. K. (2019) · Journal of Experimental Medicine · doi:10.1084/jem.20180794 · Cited by 471 · see citing works
Defects in trafficking bridge Parkinson’s disease pathology and genetics
Abeliovich, A., & Gitler, A. D. (2016) · Nature · doi:10.1038/nature20414 · Cited by 462 · see citing works
Mhyre, T. R., Boyd, J. T., Hamill, R. W., & Maguire‐Zeiss, K. A. (2012) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-94-007-5416-4_16 · Cited by 442 · see citing works
“A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript Maguire-Zeiss et al. 2008; Reynolds et al. 2008; Su et al. 2008; Theodore et al. 2008; Su et al. 2009; Lee et al. 2010; Beraud et al. 2011).”
BackgroundSelf-citationLinking Neuroinflammation and Neurodegeneration in Parkinson's Disease
Gelders, G., Baekelandt, V., & Van der Perren, A. (2018) · Journal of Immunology Research · doi:10.1155/2018/4784268 · Cited by 430 · see citing works
“Microglial activation lymphocytic infiltration [66, 68, 69]”
BackgroundMicroglia Mediated Neuroinflammation in Parkinson’s Disease
Işık, S., Yeman-Kıyak, B., Akbayır, R., Şeyhali-Abutayeh, R., & Arpaci, T. (2023) · Cells · doi:10.3390/cells12071012 · Cited by 402 · see citing works
Theodore, S., Cao, S., McLean, P. J., & Standaert, D. G. (2008) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e31818e5e99 · Cited by 367 · see citing works
“Early activation of microglia is also present in a transgenic mouse model of PD in which wild-type human >-SYN is expressed under a tyrosine hydroxylase promoter (31).”
Vegeto, E., Benedusi, V., & Maggi, A. C. (2008) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2008.04.001 · Cited by 356 · see citing works
Targeting Microglial Activation States as a Therapeutic Avenue in Parkinson’s Disease
Subramaniam, S., & Federoff, H. J. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00176 · Cited by 343 · see citing works
Self-citationThe Role of Oxidative Stress in Parkinson’s Disease
Chang, K., & Chen, C. (2020) · Antioxidants · doi:10.3390/antiox9070597 · Cited by 357 · see citing works
Microglial Dynamics and Role in the Healthy and Diseased Brain: A Paradigm of Functional Plasticity
Gomez-Nicola, D., & Perry, V. H. (2015) · The Neuroscientist · doi:10.1177/1073858414530512 · Cited by 340 · see citing works
The Role of Innate and Adaptive Immunity in Parkinson's Disease
Kannarkat, G. T., Boss, J. M., & Tansey, M. G. (2013) · Journal of Parkinson’s Disease · doi:10.3233/jpd-130250 · Cited by 324 · see citing works
“In response to these stimuli, microglia produce cytokines [59, 61, 62], reactive oxygen species [63, 64], prostanoids that have immunomodulatory functions [65], and chemokines that recruit peripheral immune cells [66, 67].”
BackgroundDaniele, S. G., Béraud, D., Davenport, C., Cheng, K., Yin, H., & Maguire-Zeiss, K. A. (2015) · Science Signaling · doi:10.1126/scisignal.2005965 · Cited by 303 · see citing works
“2 ng endotoxin/ml], consistent with our previous reports (48, 52).”
BackgroundResultInfluentialSelf-citationMicroglial phenotypes in Parkinson’s disease and animal models of the disease
Joers, V., Tansey, M. G., Mulas, G., & Carta, A. R. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2016.04.006 · Cited by 285 · see citing works
“Similarly, one-month old TH α-synuclein mice displayed an increase of Iba1-positive ameboid shaped microglia in the SN and increased expression of TNF in both the SN and striatum (Su et al., 2008).”
BackgroundInfluentialHarischandra, D. S., Ghaisas, S., Zenitsky, G. D., Jin, H., Kanthasamy, A., Anantharam, V., & Kanthasamy, A. G. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00654 · Cited by 290 · see citing works
DAMPs as mediators of sterile inflammation in aging-related pathologies
Feldman, N., Rotter-Maskowitz, A., & Okun, E. (2015) · Ageing Research Reviews · doi:10.1016/j.arr.2015.01.003 · Cited by 283 · see citing works
“Importantly, -synuclein activates microglia through a mechanism that involves CD36; however other PRRs also seem to respond to -synuclein, as microglia derived from CD36 knockout mice are still activated following exposure to -synuclein, albeit to a lesser extent (Su et al., 2008, 2009).”
BackgroundTumor necrosis factor-alpha mediated signaling in neuronal homeostasis and dysfunction
Park, K. M., & Bowers, W. J. (2010) · Cellular Signalling · doi:10.1016/j.cellsig.2010.01.010 · Cited by 282 · see citing works
Dzamko, N., Gysbers, A., Perera, G., Bahar, A., Shankar, A., Gao, J., Fu, Y., & Halliday, G. M. (2017) · Acta Neuropathologica · doi:10.1007/s00401-016-1648-8 · Cited by 273 · see citing works
“Recent reports have suggested that α-synuclein is a DAMP, capable of modulating inflammatory cytokine production in microglia [1, 3, 21, 39, 47].”
BackgroundThe Contribution of Microglia to Neuroinflammation in Parkinson’s Disease
Badanjak, K., Fixemer, S., Smajić, S., Skupin, A., & Grünewald, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094676 · Cited by 281 · see citing works
“In addition, both, treatment of primary mouse microglia with α-synuclein and α-synuclein OE in mice, are known to give rise to microglial ROS, TNF-α, IL-1β, COX2, iNOS [82,83].”
BackgroundPeriphery and brain, innate and adaptive immunity in Parkinson’s disease
Harms, A. S., Ferreira, S. A., & Romero‐Ramos, M. (2021) · Acta Neuropathologica · doi:10.1007/s00401-021-02268-5 · Cited by 279 · see citing works
Jang, A., Lee, H., Suk, J., Jung, J., Kim, K., & Lee, S. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.06695.x · Cited by 281 · see citing works
“A number of studies have shown that extracellular a-synuclein can activate microglia in culture, inducing an inflammatory response (Klegeris et al. 2008; Reynolds et al. 2008; Su et al. 2008; Zhang et al. 2005).”
BackgroundThe role of Toll-like receptors and neuroinflammation in Parkinson’s disease
Heidari, A., Yazdanpanah, N., & Rezaei, N. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-022-02496-w · Cited by 275 · see citing works
“Moreover, microglial activation was also observed in human α-synuclein-overexpressing transgenic mice [67].”
BackgroundLee, E.-J., Woo, M.-S., Moon, P., Baek, M., Choi, I.-Y., Kim, W.-K., Junn, E., & Kim, H.-S. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0903480 · Cited by 267 · see citing works
“(20) found that CD36 (a microglial scavenger receptor) mediates ROS production, ERK phosphorylation, and proinflammatory cytokine expression in a-synuclein–stimulated microglia.”
BackgroundFyn 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 255 · see citing works
“TLR4, CD36, and Fc γ R-deficient microglia have exhibited attenuated neuroinflammatory responses to α Syn treatment (Su et al., 2008; Cao et al., 2012; Fellner et al., 2013).”
Sanchez-Guajardo, V., Febbraro, F., Kirik, D., & Romero-Ramos, M. (2010) · PLoS ONE · doi:10.1371/journal.pone.0008784 · Cited by 256 · see citing works
“This relationship between a-syn and microglia activation has also been reported in vivo [50,51,62].”
BackgroundTargeting TNF-Alpha to Elucidate and Ameliorate Neuroinflammation in Neurodegenerative Diseases
Frankola, K. A., Greig, N. H., Luo, W., & Tweedie, D. (2011) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/187152711794653751 · Cited by 252 · see citing works
Watson, M. B., Richter, F., Lee, S., Gabby, L. C., Wu, J. E., Masliah, E., Effros, R. B., & Chesselet, M. (2012) · Experimental Neurology · doi:10.1016/j.expneurol.2012.06.025 · Cited by 241 · see citing works
“…expression can trigger microglial activation and cytokine production prior to the loss of dopaminergic neurons, suggesting that inflammation can contribute to the pathological process that eventually leads to cell death (Su et al., 2008; Theodore et al., 2008; Sanchez-Guajardo et al., 2010).”
BackgroundInfluentialSánchez-Guajardo, V., Barnum, C. J., Tansey, M. G., & Romero‐Ramos, M. (2013) · ASN NEURO · doi:10.1042/an20120066 · Cited by 237 · see citing works
“…subtype2 knockout Lack of EP2 abolished MPTP-induced ↑ aggregated α-syn In vitro EP2 knockout microglia has ↑ ability to clear α-syn Miller et al., 2007, Su et al., 2008, 2009 DM A30P-A53T * Overexpression under TH promoter Mouse C57/Bl6 ↑% of activated Iba-1 + cells in SN ↑mRNA TGFβ SN and…”
BackgroundInfluentialMicroglia in the CNS: Immigrants from another world
Prinz, M., & Mildner, A. (2010) · Glia · doi:10.1002/glia.21104 · Cited by 236 · see citing works
“The potential pathway leading to microglial activation comprises the MPTP-dependent production and release of misfolded a-synuclein by DN (Dauer and Przedborski, 2003), which in turn can activate microglia (Su et al., 2007; Zhang et al., 2005).”
BackgroundThe changing phenotype of microglia from homeostasis to disease
Luo, X., & Chen, S. (2012) · Translational Neurodegeneration · doi:10.1186/2047-9158-1-9 · Cited by 232 · see citing works
“α-synuclein Lee et al., 2010; Su et al., 2008; Zhang et al., 2005 [55-57] amyloid-beta Jana et al., 2008 [58] fibrinogen Piers et al., 2011 [59] Thrombin Lee et al., 2005 [60] Tissue plasminogen activator Siao et al., 2002 [61] Matrix protein (vitronectin, fibronectin, MMP-3) Milner et al., 2007;…”
BackgroundMicroglia in Parkinson's disease
Ho, M. S. (2019) · Advances in Experimental Medicine and Biology · doi:10.1007/978-981-13-9913-8_13 · Cited by 227 · see citing works
Inflammation is genetically implicated in Parkinson’s disease
Dzamko, N., Geczy, C. L., & Halliday, G. M. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2014.10.028 · Cited by 222 · see citing works
Microglia Response During Parkinson’s Disease: Alpha-Synuclein Intervention
Ferreira, S. A., & Romero‐Ramos, M. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00247 · Cited by 220 · see citing works
“Wake, H., Moorhouse, A. J., Miyamoto, A., and Nabekura, J. (2013). Microglia: actively surveying and shaping neuronal circuit structure and function.”
BackgroundMicroglia as modulators of exosomal alpha-synuclein transmission
Xia, Y. F., Zhang, G., Han, C., Ma, K., Guo, X., Wan, F. J., Kou, L., Yin, S., Liu, L., Huang, J., et al. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-1404-9 · Cited by 208 · see citing works
Brkic, M., Balusu, S., Libert, C., & Vandenbroucke, R. E. (2015) · Mediators of Inflammation · doi:10.1155/2015/620581 · Cited by 205 · see citing works
“involved in alteration of α-synuclein protein conformation, thus contributing to aggregation, Lewy body formation, and microglial activation [227].”
BackgroundGlia 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 202 · see citing works
“primary microglial cells causes a dose-dependent release of proinflammatory molecules (Klegeris et al., 2008; Su et al., 2008).”
M1 and M2 immune activation in Parkinson’s Disease: Foe and ally?
Moehle, M. S., & West, A. B. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.11.018 · Cited by 198 · see citing works
“Neuroscience (2014), TLR4 and CD11b, largely depending on the constituency of the protein aggregates applied to cells (Zhang et al., 2007; Su et al., 2008; Lee et al., 2010).”
BackgroundInfluentialα-Synuclein Alters Toll-Like Receptor Expression
Béraud, D., Twomey, M. A., Bloom, B., Mittereder, A., Ton, V., Neitzke, K., Chasovskikh, S., Mhyre, T. R., & Maguire‐Zeiss, K. A. (2011) · Frontiers in Neuroscience · doi:10.3389/fnins.2011.00080 · Cited by 199 · see citing works
“…leads to increased numbers of activated microglia in mouse models of α-synuclein overexpression prior to SNpc dopamine neuron death and has a direct effect on microglial activation in cell culture experiments (Zhang et al., 2005; Su et al., 2008, 2009; Theodore et al., 2008; Lee et al., 2010).”
BackgroundMethodInfluentialSelf-citationInflammation in Parkinson's Disease
Tüfekçi, K. U., Meuwissen, R. L. J., Genç, Ş., & Genç, K. (2012) · Advances in protein chemistry and structural biology · doi:10.1016/b978-0-12-398314-5.00004-0 · Cited by 199 · see citing works
Chakraborty, R., Nonaka, T., Hasegawa, M., & Zurzolo, C. (2023) · Cell Death & Disease · doi:10.1038/s41419-023-05835-8 · Cited by 190 · see citing works
Ten Unsolved Questions About Neuroinflammation in Parkinson's Disease
Hirsch, É. C., & Standaert, D. G. (2020) · Movement Disorders · doi:10.1002/mds.28075 · Cited by 191 · see citing works
Alpha-synuclein release by neurons activates the inflammatory response in a microglial cell line
Alvarez‐Erviti, L., Couch, Y., Richardson, J. C., Cooper, J. A. D., & Wood, M. J. A. (2011) · Neuroscience Research · doi:10.1016/j.neures.2010.12.020 · Cited by 193 · see citing works
“…activated microglial cells by interaction with cience C a i f c W m i e e 2 i M M t f e o f p r r t c p e s M s o w T t a o d A c m a r c M t t C A f R A B L. Alvarez-Erviti et al. / Neuros D36 receptor (Su et al., 2008), Mac-1 receptor (Zhang et al., 2007) nd other uncharacterised mechanisms.”
BackgroundResultNeuroinflammation and Parkinson’s Disease—From Neurodegeneration to Therapeutic Opportunities
Araújo, B., Caridade-Silva, R., Soares-Guedes, C., Martins‐Macedo, J., Gomes, E. D., Monteiro, S., & Teixeira, F. G. (2022) · Cells · doi:10.3390/cells11182908 · Cited by 197 · see citing works
“Accordingly, in transgenic animal models with overexpression or mutation (A53T and A30P) of α-Syn, increased numbers of activated microglia and release of proinflammatory molecules were reported, showing that this process can occur before the degeneration of the DAn and the appearance of PD motor symptomatology [103,1…”
BackgroundKrashia, P., Cordella, A., Nobili, A., La Barbera, L., Federici, M., Leuti, A., Campanelli, F., Natale, G., Marino, G., Calabrese, V., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11928-w · Cited by 188 · see citing works
Exogenous α-synuclein induces toll-like receptor 4 dependent inflammatory responses in astrocytes
Rannikko, E. H., Weber, S. S., & Kahle, P. J. (2015) · BMC Neuroscience · doi:10.1186/s12868-015-0192-0 · Cited by 185 · see citing works
“with recombinant αSYN produced in bacteria as well as cell culture medium from cells that overexpress αSYN induces neuroinflammatory responses in microglia and astroglia [26, 27, 36–38].”
Enhanced Phosphatase Activity Attenuates α-Synucleinopathy in a Mouse Model
Lee, K.-W., Chen, W. W., Junn, E., Im, J., Grosso, H., Sonsalla, P. K., Feng, X., Ray, N., Fernandez, J. R., Chao, Y., et al. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.6513-10.2011 · Cited by 184 · see citing works
“Although -Syn-mediated microglial activation has been reported in mouse models of -Syn overexpression (Su et al., 2008; Theodore et al., 2008), it is unknown whether S129 phosphorylated -Syn is a stronger trigger of this reactive process than unphosphorylated -Syn.”
BackgroundAmyloid fibrils are the molecular trigger of inflammation in Parkinson's disease
Gustot, A., Gallea, J. I., Sarroukh, R., Celej, M. S., Ruysschaert, J., & Raussens, V. (2015) · Biochemical Journal · doi:10.1042/bj20150617 · Cited by 183 · 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
Immune system responses in Parkinson's disease: Early and dynamic
Tansey, M. G., & Romero‐Ramos, M. (2018) · European Journal of Neuroscience · doi:10.1111/ejn.14290 · Cited by 183 · see citing works
“Multiple labs have shown now that asyn can initiate a proinflammatory response in microglia inducing production of IL6, IL- 1β, and TNF (Couch, AlvarezErviti, Sibson, Wood, & Anthony, 2011; Klegeris et al., 2008; Lee et al., 2009, 2010; Roodveldt et al., 2010; Su et al., 2008).”
BackgroundInfluentialBéraud, D., Hathaway, H. A., Trecki, J., Chasovskikh, S., Johnson, D. A., Johnson, J. A., Federoff, H. J., Shimoji, M., Mhyre, T. R., & Maguire‐Zeiss, K. A. (2012) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-012-9401-0 · Cited by 175 · see citing works
“In vitro studies confirm that α-synuclein is localized to cell membranes, released from cells including neurons (Lee et al. 2005; Su et al. 2008; Emmanouilidou et al. 2010a; Feng et al. 2010; Jang et al. 2010) and taken up by surrounding glia (Lee et al.”
BackgroundMethodInfluentialSelf-citationNeuroinflammation in Parkinson’s Disease
Lee, J., Tran, T. A. T., & Tansey, M. G. (2009) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-009-9176-0 · Cited by 174 · see citing works
“Evidence in support of this idea comes from studies in mice in which overexpression of wild-type α-synuclein in neurons is associated with early microglia activation, and release of α-synuclein from an αsynuclein-overexpressing DA neuron-like cell line triggers a cascade of inflammatory mediators that include TNF, IL-…”
ResultManganese promotes the aggregation and prion-like cell-to-cell exosomal transmission of α-synuclein
Harischandra, D. S., Rokad, D., Neal, M. P., Ghaisas, S., Manne, S., Sarkar, S., Panicker, N., Zenitsky, G. D., Jin, H., Lewis, M. M., et al. (2019) · Science Signaling · doi:10.1126/scisignal.aau4543 · Cited by 170 · see citing works
“Extracellular Syn reportedly interacts with CD36 (10), Toll-like receptor 4 (TLR4) (66) and TLR2 (67) and thus activates microglial Ctx”
BackgroundNeuroinflammation in Parkinson's disease: role in neurodegeneration and tissue repair
Vivekanantham, S., Shah, S., Dewji, R., Dewji, A., Khatri, C., & Ologunde, R. (2015) · International Journal of Neuroscience · doi:10.3109/00207454.2014.982795 · Cited by 171 · see citing works
“Overexpression of the wild type SYN in culture causes increased microglial expression of pro-inflammatory molecules as determined by mRNA analysis [24].”
BackgroundThe relation between α-synuclein and microglia in Parkinson’s disease: Recent developments
Sánchez-Guajardo, V., Tentillier, N., & Romero‐Ramos, M. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.02.008 · Cited by 171 · see citing works
The role of inflammation in sporadic and familial Parkinson’s disease
Deleidi, M., & Gasser, T. (2013) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-013-1352-y · Cited by 167 · see citing works
Panicker, N., Saminathan, H., Jin, H., Neal, M., Harischandra, D. S., Gordon, R., Kanthasamy, K. A., Lawana, V., Sarkar, S., Luo, J. D., et al. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.0302-15.2015 · Cited by 163 · see citing works
“The aggregated form of -synuclein, the primary component of PD-associated Lewy bodies, can activate microglia by using CD36- and TLR2dependent pathways (Su et al., 2008; Kim et al., 2013a).”
BackgroundNeural and Immune Mechanisms in the Pathogenesis of Parkinson’s Disease
Blandini, F. (2013) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-013-9435-y · Cited by 164 · see citing works
“In vivo, evidence of microglia activation is a typical finding in mice that over-express wild-type αsynuclein , along with infiltration of B and T lymphocytes in the SNc (Su et al. 2008; Theodore et al. 2008).”
BackgroundAssessment of α-Synuclein Secretion in Mouse and Human Brain Parenchyma
Emmanouilidou, E., Elenis, D., Papasilekas, T., Stranjalis, G., Gerozissis, K., Ioannou, P. C., & Vekrellis, K. (2011) · PLoS ONE · doi:10.1371/journal.pone.0022225 · Cited by 163 · see citing works
“Increases in extracellular a-synuclein could trigger toxic oligomer formation and result in inflammatory glial activation [47], finally leading to neurodegeneration.”
BackgroundExtracellular Interactions of Alpha-Synuclein in Multiple System Atrophy
Valdinocci, D., Radford, R. A. W., Goulding, M., Hayashi, J., Chung, R. S., & Pountney, D. L. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19124129 · Cited by 161 · see citing works
Zhang, Q.-S., Heng, Y., Yuan, Y.-H., & Chen, N.-H. (2017) · Toxicology Letters · doi:10.1016/j.toxlet.2016.11.002 · Cited by 156 · see citing works
Glial dysfunction in the pathogenesis of α-synucleinopathies: emerging concepts
Fellner, L., Jellinger, K. A., Wenning, G. K., & Stefanova, N. (2011) · Acta Neuropathologica · doi:10.1007/s00401-011-0833-z · Cited by 162 · see citing works
“Enhanced dose-dependent release of pro-inflammatory molecules was reported upon a-synuclein treatment of primary microglial cells in vitro [115, 228].”
BackgroundDrouin-Ouellet, J., St-Amour, I., Saint-Pierre, M., Lamontagne-Proulx, J., Kriz, J., Barker, R. A., & Cicchetti, F. (2015) · International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyu103 · Cited by 153 · see citing works
“In particular, aggregated forms of this protein secreted by neurons of the substantia nigra (SN) could do this, leading to the production of proinflammatory mediators and thereby exacerbating neuronal death (Zhang et al., 2005; Su et al., 2008; Theodore et al., 2008; Lee et al., 2010).”
BackgroundManganese exposure induces neuroinflammation by impairing mitochondrial dynamics in astrocytes
Sarkar, S., Malovic, E., Harischandra, D. S., Ngwa, H. A., Ghosh, A., Hogan, C., Rokad, D., Zenitsky, G. D., Jin, H., Anantharam, V., et al. (2017) · NeuroToxicology · doi:10.1016/j.neuro.2017.05.009 · Cited by 151 · see citing works
“Furthermore, we and others have shown that aSynagg induces inflammation in microglia and astrocytes (Codolo et al., 2013; Gordon et al., 2016b; Kim et al., 2013; Su et al., 2008).”
BackgroundPark, J., Paik, S. R., Jou, I., & Park, S. M. (2008) · Glia · doi:10.1002/glia.20691 · Cited by 151 · see citing works
Toll-like receptors and their therapeutic potential in Parkinson’s disease and α-synucleinopathies
Kouli, A., Horne, C. B., & Williams-Gray, C. H. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.06.042 · Cited by 143 · see citing works
Mutant α-Synuclein Overexpression Mediates Early Proinflammatory Activity
Su, X., Federoff, H. J., & Maguire-Zeiss, K. A. (2009) · Neurotoxicity Research · doi:10.1007/s12640-009-9053-x · Cited by 145 · see citing works
“Taken together, these data demonstrate a reduced effect of DM SYN on CD36 knock-out microglia compared to C57BL/6 microglial suggesting this scavenger receptor is in part responsible for DM SYNdependent microglial activation (Su et al. 2008).”
BackgroundMethodResultInfluentialSelf-citationAstrocytes, Microglia, and Parkinson’s Disease
Joe, E.-H., Choi, D., An, J., Eun, J.-H., Jou, I., & Park, S.-M. (2018) · Experimental Neurobiology · doi:10.5607/en.2018.27.2.77 · Cited by 142 · see citing works
“Alpha-synuclein also positively regulates microglia inflammatory responses and astrocyte ICAM-1 and IL-6 expression [137-139].”
BackgroundThe immune system in Parkinson's disease: what we know so far
Roodveldt, C., Bernardino, L. I., Çakmak, Ö. Ö., Dragić, M., Fladmark, K. E., Ertan, S., Aktaş, B., Pita, C., Ciglar, L., Garraux, G., et al. (2024) · Brain · doi:10.1093/brain/awae177 · Cited by 148 · see citing works
“The intracellular degradation of pathological α -syn leads to α -syn antigen presentation, which activates CD8 + T cells (CTLs) via class-I MHC, and CD4 + (Th and Treg) cells via class-II MHC. Th1 and Th17 T cells typically potentiate pro-inflammatory and neurotoxic events, whereas Th2 and Treg T cells support the res…”
BackgroundInfluentialPharmacological Targeting of Microglial Activation: New Therapeutic Approach
Liu, C., Wang, X., Liu, C., & Zhang, H. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00514 · Cited by 141 · see citing works
Sacino, A. N., Brooks, M., McKinney, A. B., Thomas, M. A., Shaw, G., Golde, T. E., & Giasson, B. I. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.2102-14.2014 · Cited by 141 · see citing works
“…aggregated S are potent activators of inflammation (Zhang et al., 2005; Klegeris et al., 2006, 2008; Reynolds et al., 2008; Roodveldt et al., 2008; Su et al., 2008; Lee et al., 2009; Tansey and Goldberg, 2010; Alvarez-Erviti et al., 2011; Béraud et al., 2011; Codolo et al., 2013; Fellner et al.,…”
BackgroundResultMechanisms of NLRP3 priming in inflammaging and age related diseases
Gritsenko, A., Green, J., Brough, D., & López‐Castejón, G. (2020) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2020.08.003 · Cited by 143 · see citing works
“Further work revealed the role of CD36 on murine microglia in regulating α -synuclein mediated microglial activation, TNF-α production and ROS generation [127].”
BackgroundGenetic mouse models of Parkinson’s disease
Magen, I., & Chesselet, M. (2010) · Progress in brain research · doi:10.1016/s0079-6123(10)84004-x · Cited by 140 · see citing works
Misfolded α-synuclein and toll-like receptors: therapeutic targets for Parkinson's disease
Béraud, D., & Maguire‐Zeiss, K. A. (2011) · Parkinsonism & Related Disorders · doi:10.1016/s1353-8020(11)70008-6 · Cited by 135 · see citing works
“An important lingering question is how does α-synuclein activate microglia? In an in vitro system utilizing microglia derived from mice devoid of the pattern recognition receptor, CD36, α-synuclein-directed activation of microglia was diminished [9].”
BackgroundSelf-citationThe complex relationships between microglia, alpha-synuclein, and LRRK2 in Parkinson's disease
Schapansky, J., Nardozzi, J. D., & LaVoie, M. J. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2014.09.049 · Cited by 132 · see citing works
“…response in microglia, either evidenced through analysis of cytokine secretion (Klegeris et al., 2008; Lee et al., 2009; Béraud et al., 2013; Austin et al., 2006; Su et al., 2008; Couch et al., 2011)or reactive oxygen species (ROS) production (Thomas et al., 2007; Fellner et al., 2013).”
BackgroundHeat-Shock Proteins in Neuroinflammation
Dukay, B., Csoboz, B., & Tóth, M. E. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00920 · Cited by 132 · see citing works
Rab11a and HSP90 Regulate Recycling of Extracellular α-Synuclein
Liu, J., Zhang, J., Shi, M. Y., Quinn, T. J., Bradner, J. M., Beyer, R., Chen, S., & Zhang, J. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.6202-08.2009 · Cited by 133 · see citing works
“Furthermore, eSNCA has been shown to activate microglia (Croisier et al., 2005; Zhang et al., 2005; Su et al., 2008) and astroglia (Klegeris et al.”
BackgroundInnate and Adaptive Immunity for the Pathobiology of Parkinson's Disease
Stone, D. K., Reynolds, A. D., Mosley, R. L., & Gendelman, H. E. (2009) · Antioxidants and Redox Signaling · doi:10.1089/ars.2009.2460 · Cited by 130 · see citing works
“Importantly, in vivo and in vitro studies demonstrated that microglia become activated in response to overexpression of a–syn or nitrated and aggregated forms of a-syn, a major component of Lewy bodies found in the brains of PD patients (119, 130).”
BackgroundMicroglial responses to dopamine in a cell culture model of Parkinson's disease
Mastroeni, D., Grover, A., Leonard, B. W., Joyce, J. N., Coleman, P. D., Kozik, B., Bellinger, D. L., & Rogers, J. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2008.01.001 · Cited by 130 · see citing works
P2X7 receptor is critical in α-synuclein–mediated microglial NADPH oxidase activation
Jiang, T., Hoekstra, J., Heng, X., Kang, W., Ding, J., Liu, J., Chen, S., & Zhang, J. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2015.03.015 · Cited by 123 · see citing works
Reactive microglia enhance the transmission of exosomal α-synuclein via toll-like receptor 2
Xia, Y., Zhang, G., Kou, L., Yin, S., Han, C., Hu, J., Wan, F., Sun, Y., Wu, J., Li, Y., et al. (2021) · Brain · doi:10.1093/brain/awab122 · Cited by 123 · see citing works
Kim, B.-W., Koppula, S., Kumar, H., Park, J., Kim, I.-W., More, S. V., Kim, I., Han, S.-D., Kim, S., Yoon, S., et al. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.04.037 · Cited by 118 · see citing works
“, 2003) and other neurotoxins (Choi et al., 2003; Cicchetti et al., 2002; Su et al., 2008) stimulate microglia, thereby producing proinflammatory mediators such as nitric oxide (NO), prostaglandin E2, tumor necrosis factor-alpha (TNFα), interleukin (IL)-1β and IL-6 (Cao et al.”
- 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 › 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
- 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
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
