TLR9 activation via microglial glucocorticoid receptors contributes to degeneration of midbrain dopamine neurons
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Inflammation is a characteristic feature of Parkinson’s disease (PD). We examined the role of TLR9 and its regulation by glucocorticoid receptors (GRs) in degeneration of substantia nigra dopamine neurons (DNs). TLR9 agonist, CpG-ODN, induced DN degeneration in mice lacking GR in microglia but not in controls. TLR9 deletion reduced DN loss in neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. GR regulates TLR9 activation during MPTP neurotoxicity as TLR9 antagonist suppressed increased DN loss in microglia/macrophage GR mutant mice. GR absence in microglia enhanced TLR9 translocation to endolysosomes and facilitated its cleavage leading to pro-inflammatory gene expression. GR-dependent TLR9 activation also triggered DN loss following intranigral injection of mitochondrial DNA. Finally, microglial GR sensitivity to A53T-alpha-synuclein induced DN degeneration as well as decreased microglial GR expression observed in SN of PD brain samples, all suggest that reduced microglial GR activity in SN can stimulate TLR9 activation and DN loss in PD pathology.
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CpG-DNA can induce neuronal degeneration in vivo only when glucocorticoid receptors are removed.
“But CpG-DNA can induce neuronal degeneration in vivo only when glucocorticoid receptors (GRs) were removed”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [320]
The Results section reports that intranigral CpG ODN caused significant dopamine-neuron loss in mice lacking microglial/macrophage GR, but not a significant loss in control mice. The claim's “only when” is too absolute: the same section reports neuron loss after pharmacological GR inhibition with RU486, without receptor removal. The finding also concerns midbrain dopamine neurons, rather than neuronal degeneration generally. (LLM, conf=0.88)
Experimental — accuracy not yet measuredDecreased glucocorticoid receptors, observed in the brain of PD patients, enhanced activation of TLR9.
“because decreased GRs, which is observed in the brain of PD patients, enhanced the activation of TLR9.320”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [320]
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Pattern Recognition Receptors and Inflammation
Takeuchi, O., & Akira, S. (2010) · Cell · doi:10.1016/j.cell.2010.01.022 · Cited by 8,895 · see citing works
A Toll-like receptor recognizes bacterial DNA
Hemmi, H., Takeuchi, O., Kawai, T., Kaisho, T., Sato, S., Sanjo, H., Matsumoto, M., Hoshino, K., Wagner, H., Takeda, K., et al. (2000) · Nature · doi:10.1038/35047123 · Cited by 6,491 · see citing works
Circulating mitochondrial DAMPs cause inflammatory responses to injury
Zhang, Q., Raoof, M., Chen, Y., Sumi, Y., Sursal, T., Junger, W., Brohi, K., Itagaki, K., & Hauser, C. J. (2010) · Nature · doi:10.1038/nature08780 · Cited by 3,812 · see citing works
Toll-like receptors and their crosstalk with other innate receptors in infection and immunity
Kawai, T., & Akira, S. (2011) · Immunity · doi:10.1016/j.immuni.2011.05.006 · Cited by 3,658 · see citing works
A Gene Network Regulating Lysosomal Biogenesis and Function
Sardiello, M., Palmieri, M., di Ronza, A., Medina, D. L., Valenza, M., Gennarino, V. A., Di Malta, C., Donaudy, F., Embrione, V., Polishchuk, R. S., et al. (2009) · Science · doi:10.1126/science.1174447 · Cited by 2,543 · see citing works
Conditional gene targeting in macrophages and granulocytes using LysMcre mice
Clausen, B. E., Burkhardt, C., Reith, W., Renkawitz, R., & Förster, I. (1999) · Transgenic Research · doi:10.1023/a:1008942828960 · Cited by 2,143 · see citing works
Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain
Lawson, L. J., Perry, V. H., Dri, P., & Gordon, S. (1990) · Neuroscience · doi:10.1016/0306-4522(90)90229-w · Cited by 2,045 · see citing works
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 mitochondrial genome: structure, transcription, translation and replication
Taanman, J.-W. (1999) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/s0005-2728(98)00161-3 · Cited by 1,635 · 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
Mitochondrial DNA that escapes from autophagy causes inflammation and heart failure
Oka, T., Hikoso, S., Yamaguchi, O., Taneike, M., Takeda, T., Tamai, T., Oyabu, J., Murakawa, T., Nakayama, H., Nishida, K., et al. (2012) · Nature · doi:10.1038/nature10992 · Cited by 1,201 · see citing works
Microglial cell origin and phenotypes in health and disease
Saijo, K., & Glass, C. K. (2011) · Nature Reviews Immunology · doi:10.1038/nri3086 · Cited by 1,100 · see citing works
Liberatore, G. T., Jackson-Lewis, V., Vukosavic, S., Mandir, A. S., Vila, M., McAuliffe, W. G., Dawson, V. L., Dawson, T. M., & Przedborski, S. (1999) · Nature Medicine · doi:10.1038/70978 · Cited by 1,046 · see citing works
Innate immunity in the central nervous system
Ransohoff, R. M., & Brown, M. A. (2012) · Journal of Clinical Investigation · doi:10.1172/jci58644 · Cited by 1,034 · see citing works
Self-citationNeuroendocrine Regulation of Immunity
Webster, J. I., Tonelli, L., & Sternberg, E. M. (2002) · Annual Review of Immunology · doi:10.1146/annurev.immunol.20.082401.104914 · Cited by 957 · see citing works
Kim, W., Mohney, R. P., Wilson, B. C., Jeohn, G., Liu, B., & Hong, J. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-16-06309.2000 · Cited by 881 · see citing works
Saijo, K., Winner, B., Carson, C. T., Collier, J. G., Boyer, L., Rosenfeld, M. G., Gage, F. H., & Glass, C. K. (2009) · Cell · doi:10.1016/j.cell.2009.01.038 · Cited by 859 · see citing works
Kim, 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
UNC93B1 delivers nucleotide-sensing toll-like receptors to endolysosomes
Kim, Y., Brinkmann, M. M., Paquet, M.-È., & Ploegh, H. L. (2008) · Nature · doi:10.1038/nature06726 · Cited by 699 · see citing works
A new type of microglia gene targeting shows TAK1 to be pivotal in CNS autoimmune inflammation
Goldmann, T., Wieghofer, P., Müller, P. F., Wolf, Y., Varol, D., Yona, S., Brendecke, S. M., Kierdorf, K., Staszewski, O., Datta, M., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3531 · Cited by 688 · see citing works
Etiology and pathogenesis of Parkinson's disease
Schapira, A. H. V., & Jenner, P. G. (2011) · Movement Disorders · doi:10.1002/mds.23732 · Cited by 659 · see citing works
Molecular determinants of crosstalk between nuclear receptors and toll-like receptors
Ogawa, S., Lozach, J., Benner, C., Pascual, G., Tangirala, R. K., Westin, S., Hoffmann, A., Subramaniam, S., David, M., Rosenfeld, M. G., et al. (2005) · Cell · doi:10.1016/j.cell.2005.06.029 · Cited by 647 · see citing works
A rotarod test for evaluation of motor skill learning
Shiotsuki, H., Yoshimi, K., Shimo, Y., Funayama, M., Takamatsu, Y., Ikeda, K., Takahashi, R., Kitazawa, S., & Hattori, N. (2010) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2010.03.026 · Cited by 627 · see citing works
The ectodomain of Toll-like receptor 9 is cleaved to generate a functional receptor
Ewald, S. E., Lee, B. L., Lau, L., Wickliffe, K. E., Shi, G., Chapman, H. A., & Barton, G. M. (2008) · Nature · doi:10.1038/nature07405 · Cited by 616 · see citing works
A calculated response: control of inflammation by the innate immune system
Barton, G. M. (2008) · Journal of Clinical Investigation · doi:10.1172/jci34431 · Cited by 532 · see citing works
Park, B., Brinkmann, M. M., Spooner, E., Lee, C. C., Kim, Y., & Ploegh, H. L. (2008) · Nature Immunology · doi:10.1038/ni.1669 · Cited by 478 · see citing works
Ligand-induced conformational changes allosterically activate Toll-like receptor 9
Latz, E., Verma, A., Visintin, A., Gong, M., Sirois, C. M., Klein, D. C. G., Monks, B. G., McKnight, C. J., Lamphier, M. S., Duprex, W. P., et al. (2007) · Nature Immunology · doi:10.1038/ni1479 · Cited by 462 · see citing works
The pathogenesis of cell death in Parkinson's disease
Jenner, P. G., & Olanow, C. W. (2006) · Neurology · doi:10.1212/wnl.66.10_suppl_4.s24 · Cited by 451 · see citing works
Brinkmann, M. M., Spooner, E., Hoebe, K. H. N., Beutler, B., Ploegh, H. L., & Kim, Y. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200612056 · Cited by 444 · see citing works
Ghosh, A., Roy, A., Liu, X., Kordower, J. H., Mufson, E. J., Hartley, D. M., Ghosh, S., Mosley, R. L., Gendelman, H. E., & Pahan, K. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0704908104 · Cited by 438 · see citing works
Hunot, S., Vila, M., Teismann, P., Davis, R. J., Hirsch, É. C., Przedborski, S., RAKIC, P. T., & Flavell, R. A. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0307453101 · Cited by 427 · see citing works
Glia: Initiators and progressors of pathology in Parkinson's disease
Halliday, G. M., & Stevens, C. H. (2011) · Movement Disorders · doi:10.1002/mds.23455 · Cited by 423 · see citing works
Castaño, A., Herrera, A. J., Cano, J., & Machado, A. (1998) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1998.70041584.x · Cited by 393 · see citing works
Dehmer, T., Heneka, M. T., Sastre, M., DICHGANS, J., & Schulz, J. B. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.02210.x · Cited by 382 · see citing works
TLR recognition of self nucleic acids hampers glucocorticoid activity in lupus
Guiducci, C., Gong, M., Xu, Z., Gill, M. A., Chaussabel, D., Meeker, T., Chan, J. H., Wright, T. B., Punaro, M., Bolland, S. M., et al. (2010) · Nature · doi:10.1038/nature09102 · Cited by 380 · see citing works
Gao, H.-M., Zhou, H., Zhang, F., Wilson, B. C., Kam, W., & Hong, J.-S. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.3732-10.2011 · Cited by 369 · see citing works
Hartmann, A. (1997) · Neurobiology of Aging · doi:10.1016/s0197-4580(97)80309-0 · Cited by 319 · see citing works
Jang, H., Boltz, D. A., Webster, R. G., & Smeyne, R. J. (2008) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2008.08.001 · Cited by 289 · see citing works
Sepulveda, F. E., Maschalidi, S., Colisson, R., Heslop, L., Ghirelli, C., Sakka, E., Lennon‐Duménil, A., Amigorena, S., Cabanié, L., & Manoury, B. (2009) · Immunity · doi:10.1016/j.immuni.2009.09.013 · Cited by 280 · see citing works
Self-citationTuckermann, J. P., Kleiman, A., Moriggl, R., Spanbroek, R., Neumann, A., Illing, A., Clausen, B. E., Stride, B., Förster, I., Habenicht, A. J. R., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci28034 · Cited by 252 · see citing works
Self-citationRos-Bernal, F., Hunot, S., Herrero, M. T., Parnadeau, S., Corvol, J.-C., Lu, L., Alvarez-Fischer, D., Carrillo-de Sauvage, M. A., Saurini, F., Coussieu, C., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1017820108 · Cited by 231 · see citing works
Self-citationTuckermann, J. P., Kleiman, A., Moriggl, R., Spanbroek, R., Neumann, A., Illing, A., Clausen, B. E., Stride, B. D., Förster, I., Habenicht, A. J. R., et al. (2007) · HAL · Cited by 224 · see citing works
Self-citationZecca, L., Wilms, H., Geick, S., Claasen, J.-H., Brandenburg, L.-O., Holzknecht, C., Panizza, M. L., Zucca, F. A., Deuschl, G., Sievers, J., et al. (2008) · Acta Neuropathologica · doi:10.1007/s00401-008-0361-7 · Cited by 205 · see citing works
Granulin Is a Soluble Cofactor for Toll-like Receptor 9 Signaling
Park, B., Buti, L., Lee, S., Matsuwaki, T., Spooner, E., Brinkmann, M. M., Nishihara, M., & Ploegh, H. L. (2011) · Immunity · doi:10.1016/j.immuni.2011.01.018 · Cited by 176 · see citing works
Inflammation in Parkinson’s disease: role of glucocorticoids
Herrero, M.-T., Estrada, C., Maatouk, L., & Vyas, S. (2015) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2015.00032 · Cited by 175 · see citing works
Self-citationIp, C. W., Klaus, L.-C., Karikari, A. A., Visanji, N. P., Brotchie, J. M., Lang, A. E., Volkmann, J., & Koprich, J. B. (2017) · Acta Neuropathologica Communications · doi:10.1186/s40478-017-0416-x · Cited by 173 · see citing works
Monier, A., Evrard, P., Gressèns, P., & Verney, C. (2006) · The Journal of Comparative Neurology · doi:10.1002/cne.21123 · Cited by 169 · 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
Boix, J., Padel, T., & Paul, G. (2015) · Behavioural Brain Research · doi:10.1016/j.bbr.2015.01.053 · Cited by 162 · see citing works
Analysis of dopamine transporter gene expression pattern − generation of DAT‐iCre transgenic mice
Turiault, M., Parnaudeau, S., Milet, A., Parlato, R., Rouzeau, J., Lazar, M., & Tronche, F. (2007) · FEBS Journal · doi:10.1111/j.1742-4658.2007.05886.x · Cited by 114 · see citing works
Self-citationCarrillo-de Sauvage, M. Á., Maatouk, L., Arnoux, I., Pasco, M., Sanz Diez, A., Delahaye, M., Herrero, M. T., Newman, T. A., Calvo, C. F., Audinat, E., et al. (2013) · Cell Death & Differentiation · doi:10.1038/cdd.2013.108 · Cited by 114 · see citing works
Self-citationSantoro, M., Maetzler, W., Stathakos, P., Martin, H. L., Hobert, M. A., Rattay, T. W., Gasser, T., Forrester, J. V., Berg, D., Tracey, K. J., et al. (2016) · Neurobiology of Disease · doi:10.1016/j.nbd.2016.02.018 · Cited by 107 · see citing works
Deleidi, M., Hallett, P. J., Koprich, J. B., Chung, C. Y., & Ole Isacson, A. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.2400-10.2010 · Cited by 101 · see citing works
Rapid isolation of animal mitochondrial DNA by alkaline extraction
Palva, T. K., & Palva, E. T. (1985) · FEBS Letters · doi:10.1016/0014-5793(85)80122-8 · Cited by 100 · see citing works
Liver X receptor β protects dopaminergic neurons in a mouse model of Parkinson disease
Dai, Y.-B., Tan, X.-J., Wu, W.-F., Warner, M. N., & Gustafsson, J.-Α. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1210833109 · Cited by 98 · see citing works
Nadeau, S., & Rivest, S. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.6.3370 · Cited by 94 · see citing works
Genetic causes of Parkinson's disease and their links to autophagy regulation
Pan, P., & Yue, Z. (2013) · Parkinsonism & Related Disorders · doi:10.1016/s1353-8020(13)70037-3 · Cited by 52 · see citing works
Mitochondrial DNA in CSF distinguishes LRRK2 from idiopathic Parkinson's disease
Podlesniy, P., Vilas, D., Taylor, P., Shaw, L. M. J., Tolosa, E., & Trullás, R. (2016) · Neurobiology of Disease · doi:10.1016/j.nbd.2016.05.019 · Cited by 45 · see citing works
The effect of dopamine on MPTP-induced rotarod disability
Ayton, S., George, J. L., Adlard, P. A., Bush, A. I., Cherny, R. A., & Finkelstein, D. I. (2013) · Neuroscience Letters · doi:10.1016/j.neulet.2013.02.066 · Cited by 38 · see citing works
Cortisol, ACTH, and beta-endorphin after dexamethasone administration in Parkinson's dementia
Rabey, J. M., Scharf, M., Oberman, Z., Zohar, M., & Graff, E. (1990) · Biological Psychiatry · doi:10.1016/0006-3223(90)90525-7 · Cited by 36 · see citing works
Shaker, M. E., Trawick, B. N., & Mehal, W. Z. (2016) · Biochemical Pharmacology · doi:10.1016/j.bcp.2016.05.003 · Cited by 34 · see citing works
Self-citationHoque, R., Farooq, A., Malik, A. F., Trawick, B. N., Berberich, D. W., McClurg, J. P., Galen, K. P., & Mehal, W. Z. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1202184 · Cited by 34 · see citing works
Self-citationTLR9 regulation by proteolysis: A friend or a foe
Manoury, B. (2011) · European Journal of Immunology · doi:10.1002/eji.201141858 · Cited by 13 · see citing works
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Flagged first, then by citations
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Role of neuroinflammation in neurodegeneration development
Zhang, W., Xiao, D., Mao, Q., & Xia, H. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01486-5 · Cited by 1,668 · see citing works
Microglia and astrocyte dysfunction in parkinson's disease
Kam, T., Hinkle, J. T., Dawson, T. M., & Dawson, V. L. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.105028 · Cited by 399 · see citing works
Dopamine, Immunity, and Disease
Channer, B., Matt, S. M., Nickoloff-Bybel, E. A., Pappa, V., Agarwal, Y., Wickman, J. R., & Gaskill, P. J. (2022) · Pharmacological Reviews · doi:10.1124/pharmrev.122.000618 · Cited by 325 · see citing works
The 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
Picca, A., Guerra, F., Calvani, R., Romano, R., Coelho-Júnior, H. J., Bucci, C., & Marzetti, E. (2021) · Biomolecules · doi:10.3390/biom11101508 · Cited by 189 · see citing works
Krashia, 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
Pharmacological modulation of nucleic acid sensors - therapeutic potential and persisting obstacles
Vanpouille-Box, C., Hoffmann, J. A., & Galluzzi, L. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0043-2 · Cited by 183 · see citing works
The Role of Glucocorticoids in Inflammatory Diseases
Reichardt, S. D., Amouret, A., Muzzi, C., Vettorazzi, S., Tuckermann, J. P., Lühder, F., & Reichardt, H. M. (2021) · Cells · doi:10.3390/cells10112921 · Cited by 180 · 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
Federico, S., Pozzetti, L., Papa, A., Carullo, G., Gemma, S., Butini, S., Campiani, G., & Relitti, N. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01049 · Cited by 120 · see citing works
Toll-like receptor-mediated neuroinflammation: relevance for cognitive dysfunctions
Squillace, S., & Salvemini, D. (2022) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2022.05.004 · Cited by 117 · see citing works
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Hallett, P. J., Engelender, S., & Ole Isacson, A. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1532-2 · Cited by 105 · see citing works
Formation of memory assemblies through the DNA-sensing TLR9 pathway
Jovasevic, V., Wood, E. M., Cicvaric, A., Zhang, H., Petrovic, Z., Carboncino, A., Parker, K., Bassett, T. E., Moltesen, M., Yamawaki, N., et al. (2024) · Nature · doi:10.1038/s41586-024-07220-7 · Cited by 98 · see citing works
In situ targeting nanoparticles-hydrogel hybrid system for combined chemo-immunotherapy of glioma
Wang, X., Ye, L., He, W., Teng, C., Sun, S., Lu, H., Li, S., Lv, L., Cao, X., Yin, H., et al. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.03.050 · Cited by 80 · see citing works
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Duitama, M., Vargas-López, V., Casas, Z., Albarracín, S. L., Sutachan, J. J., & Torres, Y. P. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00782 · Cited by 80 · see citing works
Picard, K., St‐Pierre, M., Vecchiarelli, H. A., Bordeleau, M., & Tremblay, M. (2021) · Neurochemistry International · doi:10.1016/j.neuint.2021.104987 · Cited by 79 · see citing works
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Alexaki, V. I. (2021) · Cells · doi:10.3390/cells10071584 · Cited by 83 · see citing works
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Zhang, G., Wei, H., Zhao, A., Xu, Y., Zhang, X., Gan, J., Guo, M., Wang, J., Zhang, F., Jiang, Y., et al. (2025) · Journal of Neuroinflammation · doi:10.1186/s12974-025-03363-0 · Cited by 81 · see citing works
Soraci, L., Gambuzza, M. E., Biscetti, L., Laganà, P., Russo, C. L., Buda, A., Barresi, G., Corsonello, A., Lattanzio, F., Lorello, G., et al. (2022) · Journal of Neurology · doi:10.1007/s00415-022-11491-3 · Cited by 72 · see citing works
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Xiong, L., McCoy, M. G., Komuro, H., West, X. Z., Yakubenko, V. P., Gao, D., Dudiki, T., Milo, A., Chen, J. M., Podrez, E. A., et al. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.11.031 · Cited by 51 · see citing works
Kang, H., Liu, Y., Li, Y., Wang, L., Zhao, Y., Yuan, R., Yang, M.-M., Chen, Y., Zhang, H., Zhou, F., et al. (2022) · Neural Regeneration Research · doi:10.4103/1673-5374.363819 · Cited by 50 · see citing works
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Solberg, R., Lunde, N. N., Forbord, K. M., Okla, M., Kassem, M. S., & Jafari, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232415983 · Cited by 52 · see citing works
Cui, W., Zhan, Y., Shao, X., Fu, W., Xiao, D., Zhu, J., Qin, X., Zhang, T., Zhang, M., Zhou, Y., et al. (2019) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.9b10308 · Cited by 49 · see citing works
Han, N., Kim, Y.-K., Ahn, S., Hwang, T., Lee, H., & Park, H. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.599045 · Cited by 50 · see citing works
Saitoh, B.-Y., Tanaka, E., Yamamoto, N., Kruining, D. V., Iinuma, K., Nakamuta, Y., Yamaguchi, H., Yamasaki, R., Matsumoto, K., & Kira, J.-I. (2021) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2021.04.008 · Cited by 47 · see citing works
Li, S., Bi, G., Han, S., & Huang, R. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2021.744942 · Cited by 45 · see citing works
Prevention of Oxidative Stress and Diseases by Antioxidant Supplementation
Martemucci, G., Portincasa, P., Centonze, V., Mariano, M., Khalil, M., & D‘Alessandro, A. G. (2022) · Medicinal Chemistry · doi:10.2174/1573406419666221130162512 · Cited by 44 · see citing works
Park, W., Seong, K., Han, H. H., Yang, S. Y., & Hahn, S. K. (2021) · RSC Advances · doi:10.1039/d1ra00747e · Cited by 40 · see citing works
Inflammation and Parkinson's disease pathogenesis: Mechanisms and therapeutic insight
Forloni, G., Vitola, P. L., Cerovic, M., & Balducci, C. (2020) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2020.11.001 · Cited by 39 · see citing works
Fan, Z., Jia, M., Zhou, J. P., Zhu, Z., Wu, Y., Lin, X., Qian, Y., Lian, J., Hua, X., Dong, J., et al. (2024) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-23-01256 · Cited by 39 · see citing works
Yuan, T., Manohar, K., Latorre, R., Orock, A., & Greenwood-Van Meerveld, B. (2020) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2020.04.020 · Cited by 35 · see citing works
Impact of sex on neuroimmune contributions to Parkinson’s disease
Bourque, M., Morissette, M., Soulet, D., & Paolo, T. D. (2023) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2023.110668 · Cited by 34 · see citing works
Toll-like Receptors as a Novel Therapeutic Target for Natural Products Against Chronic Diseases
Narayanankutty, A. (2019) · Current Drug Targets · doi:10.2174/1389450120666190222181506 · Cited by 29 · see citing works
Asparagine endopeptidase cleaves tau at N167 after uptake into microglia
Behrendt, A., Bichmann, M., Ercan-Herbst, E., Haberkant, P., Schöndorf, D. C., Wolf, M., Fahim, S. A., Murolo, E., & Ehrnhoefer, D. E. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.104518 · Cited by 26 · see citing works
Glial Cell Dynamics in Neuroinflammation: Mechanisms, Interactions, and Therapeutic Implications
García‐Domínguez, M. (2026) · Biomedicines · doi:10.3390/biomedicines14010115 · Cited by 29 · see citing works
Is Pre‐Symptomatic Immunosuppression Protective in CSF1R ‐ Related Leukoencephalopathy?
Tipton, P. W., Stanley, E. R., Chiţu, V., & Wszołek, Z. K. (2021) · Movement Disorders · doi:10.1002/mds.28515 · Cited by 25 · see citing works
Wei, J., Dai, S., Pu, C., Luo, P., Yang, Y., Jiang, X., Li, X., Lin, W. J., & Fei, Z. (2022) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.13919 · Cited by 23 · see citing works
Toll-like Receptors in Viral Encephalitis
Gern, O. L., Mulenge, F., Pavlou, A., Ghita, L., Steffen, I., Stangel, M., & Kalinke, U. (2021) · Viruses · doi:10.3390/v13102065 · Cited by 23 · see citing works
Host immune responses in the central nervous system during fungal infections
Reyes, E. Y., & Shinohara, M. L. (2022) · Immunological Reviews · doi:10.1111/imr.13101 · Cited by 22 · see citing works
Host-pathogen protein-nucleic acid interactions: A comprehensive review
Jain, A., Mittal, S., Tripathi, L. P., Nussinov, R., & Ahmad, S. (2022) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2022.08.001 · Cited by 21 · see citing works
Singh, G., & Khatri, D. K. (2024) · Network Modeling Analysis in Health Informatics and Bioinformatics · doi:10.1007/s13721-024-00445-6 · Cited by 20 · see citing works
Glucocorticosteroids Effects on Brain Development in the Preterm Infant: A Role for Microglia?
Zinni, M., Pansiot, J., Billion, E., Baud, O., & Mairesse, J. (2021) · Current Neuropharmacology · doi:10.2174/1570159x19666210517112913 · Cited by 15 · see citing works
TLR2 deficiency is beneficial at the late phase in MPTP-induced Parkinson’ disease mice
He, Y., Zhao, J., Dong, H., Zhang, X., Duan, Y., Ma, Y., Yu, M., Fei, J., & Huang, F. P. (2023) · Life Sciences · doi:10.1016/j.lfs.2023.122171 · Cited by 13 · see citing works
What Can Inflammation Tell Us about Therapeutic Strategies for Parkinson’s Disease?
Xue, J., Tao, K., Wang, W., & Wang, X. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25031641 · Cited by 16 · see citing works
α-synuclein in Parkinson’s disease: a central point of convergence with depression
Yusuf, A. M., İlçe, B. Y., Alhaj, H. A., & Hamoudi, R. (2025) · npj Parkinson s Disease · doi:10.1038/s41531-025-01167-w · Cited by 12 · see citing works
Mitochondrial Dysfunction in the Inflammatory Process of Neurodegenerative Diseases
Nesci, S. (2026) · Biomedicines · doi:10.3390/biomedicines14030682 · Cited by 12 · see citing works
Yuan, T., Orock, A. M., & Meerveld, B. G. (2021) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00307.2021 · Cited by 12 · see citing works
Habas, A., Natala, S. R., Bowden-Verhoek, J. K., Stocking, E. M., Price, D. L., Wrasidlo, W., Bonhaus, D. W., & Gill, M. B. (2022) · International Journal of Inflammation · doi:10.1155/2022/2337363 · Cited by 12 · see citing works
Liu, J., Ke, P., Guo, H., Gu, J., Liu, Y., Tian, X., Wang, X., & Xiao, F. (2023) · Experimental & Molecular Medicine · doi:10.1038/s12276-023-01000-5 · Cited by 11 · see citing works
TLR9 activation in large wound induces tissue repair and hair follicle regeneration via γδT cells
Li, X., An, T., Yang, Y., Xu, Z., Chen, S., Yi, Z., Chen, D., Zhou, F., Man, Y., & Hu, C. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-06994-y · Cited by 12 · see citing works
Graphene promotes lung cancer metastasis through Wnt signaling activation induced by DAMPs
Bi, Z., Li, L., Yang, J., Li, X., Mo, F., Lu, T., Song, Y., Cheng, Z., Fu, Q., Lei, H., et al. (2021) · Nano Today · doi:10.1016/j.nantod.2021.101175 · Cited by 11 · see citing works
Augusto‐Oliveira, M., Tremblay, M., & Verkhratsky, A. (2024) · Advances in neurobiology · doi:10.1007/978-3-031-55529-9_6 · Cited by 10 · see citing works
Supramolecular organizing centers at the interface of inflammation and neurodegeneration
Sušjan, P., Ramuta, T. Ž., Boršić, E., Orehek, S., & Hafner‐Bratkovič, I. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.940969 · Cited by 10 · see citing works
Yang, L., Fan, S., Sun, L., Han, J., Wang, M., & Yu, T. (2025) · Frontiers in Neurology · doi:10.3389/fneur.2025.1643305 · Cited by 9 · see citing works
Immunoregulatory Functions of Nuclear Receptors: Mechanisms and Therapeutic Implications
Zhao, L., Gimple, R. C., Yang, Z., Wei, Y., Gustafsson, J.-Α., & Zhou, S. (2019) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2019.10.002 · Cited by 9 · see citing works
Crosstalk Between Mitochondrial DNA and Immune Response: Focus on Autism Spectrum Disorder
Qu, W., Yan, G., Du, Y., Zhou, X., Huang, C., Li, B., Zhou, J., & Li, Q. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-04637-z · Cited by 8 · see citing works
Cellular Communication Networks Mediated by Microglia in Ischemic Stroke
Ma, F., Bai, Y., Li, N., Cai, X., Xu, R., & Cao, X. (2025) · CNS Neuroscience & Therapeutics · doi:10.1002/cns.70687 · Cited by 8 · see citing works
Duzhong Fang Attenuates the POMC-Derived Neuroinflammation in Parkinsonian Mice
Li, L., Fan, S., Zhang, W., Li, D., Yang, Z. Y., Zhuang, P., Han, J., Guo, H., & Zhang, Y. (2021) · Journal of Inflammation Research · doi:10.2147/jir.s316314 · Cited by 8 · see citing works
Broken strands, broken minds: Exploring the nexus of DNA damage and neurodegeneration
Stavgiannoudaki, I., Goulielmaki, E., & Garinis, G. A. (2024) · DNA repair · doi:10.1016/j.dnarep.2024.103699 · Cited by 8 · see citing works
Mechanism of Microglial Cell Activation in the Benzophenone-3 Exposure Model
Maciejska, A., Pomierny, B., Krzyżanowska, W., Starek‐Świechowicz, B., Skórkowska, A., & Budziszewska, B. (2023) · Neuroscience · doi:10.1016/j.neuroscience.2023.10.002 · Cited by 7 · see citing works
Wu, Y., Hu, Q., Wu, X., Cai, Y., Zhang, Y.-Z., Wu, Y., Zhu, G., Luo, J., Cheng, H.-B., Yu, J., et al. (2023) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2023/7857760 · Cited by 7 · see citing works
Shao, W., Huo, X., Liu, X., Zhang, Q., Hao, X., & Zhang, J. (2025) · Neurochemical Research · doi:10.1007/s11064-025-04529-1 · Cited by 6 · see citing works
The contribution of silencer variants to human diseases
Huang, D., & Ovcharenko, I. (2024) · Genome biology · doi:10.1186/s13059-024-03328-1 · Cited by 6 · see citing works
Chen, Y., Chen, H., Li, X., Mi, W., Chu, Y., Wang, Y., & Mao‐Ying, Q. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.1008203 · Cited by 6 · see citing works
The Brain‐Gut Axis in Parkinson's Disease Pathology
Ozkaya, K. S., & Browning, K. N. (2026) · Comprehensive physiology · doi:10.1002/cph4.70137 · Cited by 5 · see citing works
Calugi, L., Lenci, E., Bianchini, F., Contini, A., & Trabocchi, A. (2022) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2022.116746 · Cited by 5 · see citing works
Birkle, T. J. Y., Willems, H. M. G., Skidmore, J., & Brown, G. C. (2024) · iScience · doi:10.1016/j.isci.2024.109454 · Cited by 4 · see citing works
Innate immunity in neurons makes memories persist
Kelvington, B. A., & Abel, T. G. (2024) · Nature · doi:10.1038/d41586-024-00679-4 · Cited by 3 · see citing works
Natala, S. R., Habas, A., Stocking, E. M., Orry, A. J. W., Abagyan, R. A., Makale, M., & Wrasidlo, W. (2025) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2025.130259 · Cited by 3 · see citing works
Potential pharmacologic interventions targeting TLR signaling in placental malaria
Kobia, F., Maiti, K., Obimbo, M., Smith, R., & Gitaka, J. (2022) · Trends in Parasitology · doi:10.1016/j.pt.2022.04.002 · Cited by 3 · see citing works
Mitochondrial DNA leakage in aging: Mechanisms, pathological effects, and therapeutic horizons
Chen, Z., Wu, Q., Tian, Y., Gu, L. C. R. O. D. I., Liu, X., & Liu, J. (2026) · Genes & Diseases · doi:10.1016/j.gendis.2026.102134 · Cited by 2 · see citing works
Santoscoy, M. C., Espinoza, P., Hanlon, K. S., Yang, L., Nieland, L., Ng, C., Badr, C. E., Hickman, S. E., de la Cruz, D., Griciuc, A., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.09.25.614546 · Cited by 2 · see citing works
Xu, Y., Li, J., Ma, S., Yang, T., Shen, Z., Li, M., & Huang, Q. (2026) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2026.01.053 · Cited by 1 · see citing works
Central nervous system safety risks and evaluation strategies for mucosal vaccines: A review
Li, Q., & Bai, G. (2026) · Vaccine · doi:10.1016/j.vaccine.2026.129084 · Cited by 1 · see citing works
Bai, D., Ma, Y., Lv, L., Wang, Y., Yang, W., & Ma, Y. (2020) · Neuroscience Letters · doi:10.1016/j.neulet.2020.134755
RetractedCai, S., Li, J., & Zhang, X. (2021) · Research Square · doi:10.21203/rs.3.rs-280189/v1
Mikroglial Toll-benzeri Reseptörlerin Alzheimer ve Parkinson Hastalıklarındaki Rolü
Samur, D. N., & Özbey, G. (2021) · Akdeniz Medical Journal · doi:10.53394/akd.981907
Walz, W. (2023) · Springer eBooks · doi:10.1007/978-3-031-48105-5_13
Rocha, S. M., Gustafson, D. L., Safe, S. H., & Tjalkens, R. B. (2024) · Toxicology Research · doi:10.1093/toxres/tfae059
Additional file 1 of The contribution of silencer variants to human diseases
Huang, D., & Ovcharenko, I. (2024) · Figshare · doi:10.6084/m9.figshare.26211326
Additional file 2 of The contribution of silencer variants to human diseases
Huang, D., & Ovcharenko, I. (2024) · Figshare · doi:10.6084/m9.figshare.26211646
Additional file 3 of The contribution of silencer variants to human diseases
Huang, D., & Ovcharenko, I. (2024) · Figshare · doi:10.6084/m9.figshare.26746436
ApoE-directed CpG nano-immunoadjuvant ameliorates Alzheimer's-like pathology in mice
Huang, X., Sun, Y.-Y., Qin, Y.-R., Chen, H., Pan, T.-T., Zhao, S., Cai, Q., Zhang, X., Nie, X.-D., Feng, L., et al. (2026) · Journal of Controlled Release · doi:10.1016/j.jconrel.2026.114687
Lisinopril activates BI1 to reprogram lipid metabolism and restore autophagy in ALS
Yin, H., Ren, Z., Zhang, Y., Wang, Y., Sun, Y., Fu, X., Yan, W., Zhang, F., & ZENG, L. (2026) · Communications Biology · doi:10.1038/s42003-026-09930-2
Étude moléculaire de l'inflammation chronique dans la maladie de Parkinson
Compagnion, A. (2019) · theses.fr (ABES) · doi:10.70675/04ca138dz3131z4e24z884czbba2f7954a99
Self-citationJose, D. A., Tripathi, A., Madeshiya, A. K., Todd, T., Quevedo, J., & Pillai, A. (2026) · Discover Neuroscience · doi:10.1186/s13064-026-00248-7
Yin, Q., Ding, M., Tang, Y., Qi, Y., Qin, Y., Jin, H., Li, Y., Bao, J., Ma, S., Li, Y., et al. (2026) · EBioMedicine · doi:10.1016/j.ebiom.2026.106325
Li, C., Wang, L., Wang, F., Wang, L., Xu, L. H., Lyu, W., Shan, K., Li, J., Zhou, H., Rong, F., et al. (2026) · Journal of Neuroinflammation · doi:10.1186/s12974-026-03921-0
Regulation of the Mineralocorticoid Receptor in Physiology and Disease
Young, M. J., Fuller, P. J., Meijer, O. C., Cole, T. J., Kanki, M., Yang, J., Ho, Q. V., Karthigan, N., & Heanue, S. (2026) · Pharmacological Reviews · doi:10.1016/j.pharmr.2026.100156
Xu, L., Xiao, K., Jiang, J., Tang, Y., Yang, L., Xiao, S., Jin, X., Xiao, B., Zhou, T., Hao, C., et al. (2026) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2026.120715
Immunogenic cell death in CNS diseases: From bench to bedside
Li, P., Zhou, Z., Qing, Y., Wei, X., Mei, Z., & Zhang, W. (2026) · Ageing Research Reviews · doi:10.1016/j.arr.2026.103342
Before the insult: Why the microglial starting state matters in neurodegeneration
Szelechowski, M. (2026) · Glial health research. · doi:10.1016/j.ghres.2026.100022
Toll-like receptor signaling modulates AMPA receptor trafficking in homeostatic synaptic downscaling
Koga, A., 周平, 貴., & Matsuda, S. (2026) · The Journal of Physiological Sciences · doi:10.1016/j.jphyss.2026.100112
- Authors
- Maatouk, L., Compagnion, A.-C., Sauvage, M.-A. C.-D., Bemelmans, A.-P., Leclere-Turbant, S., Cirotteau, V., Tohme, M., Beke, A., Trichet, M., Bazin, V., Trawick, B. N., Ransohoff, R. M., Tronche, F., Manoury, B., & Vyas, S.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Université Paris-Sud (FR)
- Sorbonne Université (FR)
- Corresponding author
- Vyas, Sheela
- ORCID
- Venue
- Nature Communications
- Published
- 2018-06-22
- Volume
- 9
- Issue
- 1
- Pages
- 2450-2450
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6015079
- OpenAlex
- W2809111018
- Cited by
- 95
- References
- 63
- Citations by year
- 2026: 16 · 2025: 6 · 2024: 15 · 2023: 7 · 2022: 18 · 2021: 18 · 2020: 6 · 2019: 9
- FWCI
- 3.71
- Type
- journal article
- Language
- en
- Update notices
- correction (2018-08-01)
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- HAL (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Agence Nationale de la Recherche (ANR-13-BSV1-0013, ANR-10-LABX-0043)
- Institut National de la Santé et de la Recherche Médicale
- Fondation pour la Recherche Médicale (13-BSV1-0013-02)
- Fondation de France
- Association France Parkinson
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- TLR9, glucocorticoid receptor, microglia, Parkinson's disease, substantia nigra, dopaminergic neuron loss, CpG oligodeoxynucleotides, MPTP-induced neurotoxicity, mitochondrial DNA, alpha-synuclein, neuroinflammation, pro-inflammatory gene expression
- MeSH terms
- Asparaginyl Endopeptidase, Aged, Aged, 80 and over, Animals, Cell Survival, Cysteine Endopeptidases, DNA, Mitochondrial, Female, Humans, Lysosomes, Male, Parkinson Disease, Receptors, Glucocorticoid, Substantia Nigra, Microglia, Mice, Knockout, Toll-Like Receptor 9, Mice, Dopaminergic Neurons
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