CX3CR1 Protein Signaling Modulates Microglial Activation and Protects against Plaque-independent Cognitive Deficits in a Mouse Model of Alzheimer Disease
Open accessAbstract
Aberrant microglial activation has been proposed to contribute to the cognitive decline in Alzheimer disease (AD), but the underlying molecular mechanisms remain enigmatic. Fractalkine signaling, a pathway mediating the communication between microglia and neurons, is deficient in AD brains and down-regulated by amyloid-β. Although fractalkine receptor (CX3CR1) on microglia was found to regulate plaque load, no functional effects have been reported. Our study demonstrates that CX3CR1 deficiency worsens the AD-related neuronal and behavioral deficits. The effects were associated with cytokine production but not with plaque deposition. Ablation of CX3CR1 in mice overexpressing human amyloid precursor protein enhanced Tau pathology and exacerbated the depletion of calbindin in the dentate gyrus. The levels of calbindin in the dentate gyrus correlated negatively with those of tumor necrosis factor α and interleukin 6, suggesting neurotoxic effects of inflammatory factors. Functionally, removing CX3CR1 in human amyloid precursor protein mice worsened the memory retention in passive avoidance and novel object recognition tests, and their memory loss in the novel object recognition test is associated with high levels of interleukin 6. Our findings identify CX3CR1 as a key microglial pathway in protecting against AD-related cognitive deficits that are associated with aberrant microglial activation and elevated inflammatory cytokines.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Complete deletion of CX3CR1 is associated with worsening memory deficits and tau pathology.
“However, such complete deletion has also been associated with worsening memory deficits and tau pathology (28–31).”
From Heterozygous CX3CR1 Deficiency in Microglia Restores Neuronal β-Amyloid Clearance Pathways and Slows Progression of Alzheimer's Like-Disease in PS1-APP Mice (2019) · cites this paper as [29]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Terry, R. D., Masliah, E., Salmon, D. P., Butters, N., DeTeresa, R., Hill, R., Hansen, L. A., & Katzman, R. (1991) · Annals of Neurology · doi:10.1002/ana.410300410 · Cited by 4,397 · see citing works
Jung, S., Aliberti, J., Graemmel, P., Sunshine, M. J., Kreutzberg, G. W., Sher, A., & Littman, D. R. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.11.4106-4114.2000 · Cited by 2,632 · see citing works
Synapse Loss and Microglial Activation Precede Tangles in a P301S Tauopathy Mouse Model
Yoshiyama, Y., Higuchi, M., Zhang, B., Huang, S.-M., Iwata, N., Saido, T. C., Maeda, J., Suhara, T., Trojanowski, J. Q., & Lee, V. M.-Y. (2007) · Neuron · doi:10.1016/j.neuron.2007.01.010 · Cited by 2,208 · see citing works
Initiative, T. A. D. N., Hollingworth, P., CHARGE consortium, EADI1 consortium, Harold, D., Sims, R., Gerrish, A., Lambert, J.-C., Carrasquillo, M. M., Abraham, R., et al. (2011) · Nature Genetics · doi:10.1038/ng.803 · Cited by 1,997 · see citing works
Microglial physiology: unique stimuli, specialized responses
Ransohoff, R. M., & Perry, V. H. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132528 · Cited by 1,858 · see citing works
Self-citationMucke, L., Masliah, E., Yu, G.-Q., Mallory, M., Rockenstein, E. M., Tatsuno, G., Hu, K., Kholodenko, D., Johnson-Wood, K., & McConlogue, L. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-11-04050.2000 · Cited by 1,856 · see citing works
Recognition memory: What are the roles of the perirhinal cortex and hippocampus?
Brown, M. W., & Aggleton, J. P. (2001) · Nature reviews. Neuroscience · doi:10.1038/35049064 · Cited by 1,555 · see citing works
Control of microglial neurotoxicity by the fractalkine receptor
Cardona, A. E., Pioro, E. P., Sasse, M. E., Kostenko, V., Cardona, S. M., Dijkstra, I. M., Huang, D., Kidd, G., Dombrowski, S., Dutta, R., et al. (2006) · Nature Neuroscience · doi:10.1038/nn1715 · Cited by 1,531 · see citing works
Self-citationSoluble Amyloid β Peptide Concentration as a Predictor of Synaptic Change in Alzheimer's Disease
Lue, L.-F., Kuo, Y.-M., Roher, A. E., Brachova, L., Shen, Y., Sue, L., Beach, T., Kurth, J. H., Rydel, R. E., & Rogers, J. (1999) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)65184-x · Cited by 1,530 · see citing works
Imai, T., Hieshima, K., Haskell, C. A., Baba, M., Nagira, M., Nishimura, M., Kakizaki, M., Takagi, S., Nomiyama, H., Schall, T. J., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)80438-9 · Cited by 1,446 · see citing works
Microglial Dysfunction and Defective β-Amyloid Clearance Pathways in Aging Alzheimer's Disease Mice
Hickman, S. E., Allison, E. K., & El Khoury, J. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.0616-08.2008 · Cited by 1,329 · see citing works
Wyss-Coray (2006) · doi:10.1038/nm1484 · Cited by 1,284 · see citing works
Inflammation in Neurodegenerative Disease—A Double-Edged Sword
Wyss-Coray, T., & Mucke, L. (2002) · Neuron · doi:10.1016/s0896-6273(02)00794-8 · Cited by 1,235 · see citing works
Genome-wide Analysis of Genetic Loci Associated With Alzheimer Disease
Seshadri, S. (2010) · JAMA · doi:10.1001/jama.2010.574 · Cited by 1,219 · see citing works
Harrison, J. K., Jiang, Y., Chen, S., Xia, Y., Maciejewski, D., McNamara, R. K., Streit, W. J., Salafranca, M. N., Adhikari, S., Thompson, D. A., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.18.10896 · Cited by 1,176 · see citing works
Recognition memory and the medial temporal lobe: a new perspective
Squire, L. R., Wixted, J. T., & Clark, R. E. (2007) · Nature reviews. Neuroscience · doi:10.1038/nrn2154 · Cited by 1,013 · see citing works
Non–cell autonomous toxicity in neurodegenerative disorders: ALS and beyond
Ilieva, H., Polymenidou, M., & Cleveland, D. W. (2009) · Journal of Cell Biology · doi:10.1083/jcb.200908164 · Cited by 1,008 · see citing works
Selective Ablation of Proliferating Microglial Cells Exacerbates Ischemic Injury in the Brain
Lalancette-Hébert, M., Gowing, G., Simard, A., Weng, Y. C., & Kriz, J. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.5360-06.2007 · Cited by 874 · see citing works
Heterogeneity of Microglial Activation in the Innate Immune Response in the Brain
Colton, C. A. (2009) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-009-9164-4 · Cited by 871 · see citing works
The myeloid cells of the central nervous system parenchyma
Ransohoff, R. M., & Cardona, A. E. (2010) · Nature · doi:10.1038/nature09615 · Cited by 804 · see citing works
Self-citationDoes neuroinflammation fan the flame in neurodegenerative diseases?
Frank-Cannon, T. C., Alto, L. T., McAlpine, F. E., & Tansey, M. G. (2009) · Molecular Neurodegeneration · doi:10.1186/1750-1326-4-47 · Cited by 751 · see citing works
SIRT1 Protects against Microglia-dependent Amyloid-β Toxicity through Inhibiting NF-κB Signaling
Chen, J., Zhou, Y., Mueller-Steiner, S., Chen, L.-F., Kwon, H., Yi, S., Mucke, L., & Gan, L. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m509329200 · Cited by 740 · see citing works
Self-citationCharacterization of the Drosophila melanogaster genome at the nuclear lamina
Pickersgill, H., Kalverda, B., de Wit, E., Talhout, W., Fornerod, M., & van Steensel, B. (2006) · Nature Genetics · doi:10.1038/ng1852 · Cited by 656 · see citing works
Regulation of Tau Pathology by the Microglial Fractalkine Receptor
Bhaskar, K., Konerth, M., Kokiko-Cochran, O. N., Cardona, A., Ransohoff, R. M., & Lamb, B. T. (2010) · Neuron · doi:10.1016/j.neuron.2010.08.023 · Cited by 639 · see citing works
Self-citationGarton, K. J., Gough, P. J., Blobel, C., Murphy, G., Greaves, D. R., Dempsey, P. J., & Raines, E. W. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m106434200 · Cited by 639 · see citing works
Johnson‐Wood, K., Lee, M., Motter, R. N., Hu, K., Gordon, G., Barbour, R., Khan, K., Gordon, M. N., Tan, H. T., Games, D., et al. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.4.1550 · Cited by 634 · see citing works
Microglial Cx3cr1 knockout prevents neuron loss in a mouse model of Alzheimer's disease
Fuhrmann, M., Bittner, T., Jung, C. K. E., Burgold, S., Page, R. M., Mitteregger, G., Haass, C., LaFerla, F. M., Kretzschmar, H., & Herms, J. (2010) · Nature Neuroscience · doi:10.1038/nn.2511 · Cited by 562 · see citing works
Lee, S., Varvel, N. H., Konerth, M. E., Xu, G., Cardona, A. E., Ransohoff, R. M., & Lamb, B. T. (2010) · The American Journal of Pathology · doi:10.2353/ajpath.2010.100265 · Cited by 539 · see citing works
Self-citationQuintanilla, R. A., Orellana, D. I., González-Billault, C., & Maccioni, R. B. (2004) · Experimental Cell Research · doi:10.1016/j.yexcr.2004.01.002 · Cited by 455 · see citing works
Inflammation and Alzheimer's disease pathogenesis
Rogers, J., Webster, S. D., Lue, L., Brachova, L., CIVIN, W. H., Emmerling, M. R., Shivers, B. D., Walker, D. G., & McGeer, P. L. (1996) · Neurobiology of Aging · doi:10.1016/0197-4580(96)00115-7 · Cited by 441 · see citing works
Inflammation, microglia, and alzheimer's disease
Cameron, B., & Landreth, G. E. (2009) · Neurobiology of Disease · doi:10.1016/j.nbd.2009.10.006 · Cited by 440 · see citing works
Palop, J. J., Jones, B., Kekonius, L., Chin, J., Yu, G.-Q., Raber, J., Masliah, E., & Mucke, L. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1133381100 · Cited by 402 · see citing works
Expression of CX <sub>3</sub> CR1 chemokine receptors on neurons and their role in neuronal survival
Meucci, O., Fatatis, A., Simen, A. A., & Miller, R. J. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.090017497 · Cited by 385 · see citing works
Production and neuroprotective functions of fractalkine in the central nervous system
Mizuno, T., Kawanokuchi, J., Numata, K., & Suzumura, A. (2003) · Brain Research · doi:10.1016/s0006-8993(03)02867-1 · Cited by 336 · see citing works
Harris, J. A., Devidze, N., Verret, L., Ho, K., Halabisky, B., Thwin, M. T., Kim, D., Hamto, P., Lo, I., Yu, G.-Q., et al. (2010) · Neuron · doi:10.1016/j.neuron.2010.10.020 · Cited by 319 · see citing works
Self-citationInterleukin‐6: a cytokine to forget
Balschun, D., Wetzel, W., del Rey, A., Pitossi, F. J., Schneider, H., Zuschratter, W., & Besedovsky, H. O. (2004) · The FASEB Journal · doi:10.1096/fj.04-1625fje · Cited by 317 · see citing works
Sparkman, N. L., Buchanan, J. B., Heyen, J. R. R., Chen, J., Beverly, J. L., & Johnson, R. W. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.3376-06.2006 · Cited by 307 · see citing works
Combadière, C., Salzwedel, K., Smith, E. D., Tiffany, H. L., Berger, E. A., & Murphy, P. M. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.37.23799 · Cited by 284 · see citing works
Liu, Z., Condello, C., Schain, A., Harb, R., & Grutzendler, J. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.4403-10.2010 · Cited by 276 · see citing works
Potter, M., Elmer, G., Bergeron, R., Albuquerque, E. X., Guidetti, P., Wu, H., & Schwarcz, R. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2010.39 · Cited by 235 · see citing works
Inflammation, anti-inflammatory agents and Alzheimer disease: The last 12 years
McGeer, P. L., Rogers, J., & McGeer, E. G. (2006) · Journal of Alzheimer s Disease · doi:10.3233/jad-2006-9s330 · Cited by 222 · see citing works
Tumor Necrosis Factor-α-converting Enzyme Mediates the Inducible Cleavage of Fractalkine
Tsou, C.-L., Haskell, C. A., & Charo, I. F. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m107327200 · Cited by 222 · see citing works
The Liberation of Fractalkine in the Dorsal Horn Requires Microglial Cathepsin S
Clark, A. K., Yip, P. K., & Malcangio, M. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.0828-09.2009 · Cited by 219 · see citing works
Microglia as a Potential Bridge between the Amyloid β‐Peptide and Tau
Kitazawa, M., Yamasaki, T. R., & LaFerla, F. M. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1332.006 · Cited by 177 · see citing works
Chemokine CX3CL1 protects rat hippocampal neurons against glutamate-mediated excitotoxicity
Limatola, C., Lauro, C., Catalano, M., Ciotti, M. T., Bertollini, C., Di Angelantonio, S., Ragozzino, D., & Eusebi, F. (2005) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2005.03.023 · Cited by 153 · see citing works
Bellinger, F. P., Madamba, S. G., Campbell, I. L., & Siggins, G. R. (1995) · Neuroscience Letters · doi:10.1016/0304-3940(95)11976-4 · Cited by 151 · see citing works
Macrophage surface glycoproteins binding to galectin-3 (Mac-2-antigen)
Dong, S., & Hughes, R. C. (1997) · Glycoconjugate Journal · doi:10.1023/a:1018554124545 · Cited by 149 · see citing works
Cardona, A. E., Sasse, M. E., Liu, L., Cardona, S. M., Mizutani, M., Savarin, C., Hu, T., & Ransohoff, R. M. (2008) · Blood · doi:10.1182/blood-2007-10-118497 · Cited by 143 · see citing works
Self-citationPittenger, C., Fasano, S., Mazzocchi‐Jones, D., Dunnett, S. B., Kandel, E. R., & Brambilla, R. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.5406-05.2006 · Cited by 103 · see citing works
Immunocytochemical evidence that amyloid β (1–42) impairs endogenous antioxidant systems in vivo
Kim, H., Yamada, K., Nitta, A., Olariu, A., Tran, M. H., Mizuno, M., Nakajima, A., Nagai, T., Kamei, H., Jhoo, W., et al. (2003) · Neuroscience · doi:10.1016/s0306-4522(02)00993-4 · Cited by 78 · see citing works
Rogers, J., Lue, L., Brachova, L., Webster, S. D., McGeer, P. L., Walker, D., Bradt, B. M., & Cooper, N. R. (1996) · Neurobiology of Aging · doi:10.1016/s0197-4580(96)80737-8 · Cited by 4 · see citing works
Zujovic (2000) · doi:10.1002/(sici)1098-1136(20000215)29:4
Flagged first, then by citations
Research works printed but not linked: 4
- Harrison, J. K., Jiang, Y., Chen, S., Xia, Y., Maciejewski, D., McNamara, R. K., Streit, W. J., Salafranca, M. N., Adhikari, S., Thompson, D. A., Botti, P., Bacon, K. B., and Feng, L. (1998) Proc. Natl. Acad. Sci. U.S.A. 95, 10896 -10901
- Meucci, O., Fatatis, A., Simen, A. A., and Miller, R. J. (2000) Proc. Natl. Acad. Sci. U.S.A. 97, 8075-8080
- Palop, J. J., Jones, B., Kekonius, L., Chin, J., Yu, G. Q., Raber, J., Masliah, E., and Mucke, L. (2003) Proc. Natl. Acad. Sci. U.S.A. 100, 9572-9577
- Johnson-Wood, K., Lee, M., Motter, R., Hu, K., Gordon, G., Barbour, R., Khan, K., Gordon, M., Tan, H., Games, D., Lieberburg, I., Schenk, D., Seubert, P., and McConlogue, L. (1997) Proc. Natl. Acad. Sci. U.S.A. 94, 1550 -1555
Cited by
Sorted by citations
Neuroinflammation in Alzheimer's disease
Heneka, M. T., Carson, M. J., Khoury, J. E., Landreth, G. E., Brosseron, F., Feinstein, D. L., Jacobs, A. H., Wyss-Coray, T., Vitorica, J., Ransohoff, R. M., et al. (2015) · The Lancet Neurology · doi:10.1016/s1474-4422(15)70016-5 · Cited by 6,226 · see citing works
Self-citationInflammation as a central mechanism in Alzheimer's disease
Kinney, J. W., Bemiller, S. M., Murtishaw, A. S., Leisgang, A. M., Salazar, A. M., & Lamb, B. T. (2018) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1016/j.trci.2018.06.014 · Cited by 2,253 · see citing works
Microglia in Alzheimer’s disease
Hansen, D. V., Hanson, J. E., & Sheng, M. (2018) · Journal of Cell Biology · doi:10.1083/jcb.201709069 · Cited by 1,935 · see citing works
“, 2010), this was reportedly accompanied by increased proinflammatory cytokines, tau pathology, and functional deficits (Cho et al., 2011; Lee et al., 2014).”
BackgroundMicroglia development and function
Nayak, D., Roth, T. L., & McGavern, D. B. (2014) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032713-120240 · Cited by 1,154 · see citing works
Innate immunity in Alzheimer's disease
Heneka, M. T., Golenbock, D. T., & Latz, E. (2015) · Nature Immunology · doi:10.1038/ni.3102 · Cited by 902 · see citing works
Inflammatory Cytokines in Experimental and Human Stroke
Lambertsen, K., Biber, K., & Finsen, B. (2012) · Journal of Cerebral Blood Flow and Metabolism · doi:10.1038/jcbfm.2012.88 · Cited by 730 · see citing works
Holtman, I. R., Raj, D. D., Miller, J. A., Schaafsma, W., Yin, Z., Brouwer, N., Wes, P. D., Möller, T., Orre, M., Kamphuis, W., et al. (2015) · Acta Neuropathologica Communications · doi:10.1186/s40478-015-0203-5 · Cited by 619 · see citing works
Self-citationMaphis, N., Xu, G., Kokiko-Cochran, O. N., Jiang, S., Cardona, A., Ransohoff, R. M., Lamb, B. T., & Bhaskar, K. (2015) · Brain · doi:10.1093/brain/awv081 · Cited by 595 · see citing works
Self-citationBidirectional Microglia–Neuron Communication in Health and Disease
Szepesi, Z., Manouchehrian, O., Bachiller, S., & Deierborg, T. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00323 · Cited by 459 · see citing works
Transcriptional signature in microglia associated with Aβ plaque phagocytosis
Grubman, A., Choo, X. Y., Chew, G., Ouyang, J. F., Sun, G., Croft, N. P., Rossello, F. J., Simmons, R., Buckberry, S., Landin, D. V., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-23111-1 · Cited by 357 · see citing works
Self-citationMicroglia, seen from the CX3CR1 angle
Wolf, Y., Yona, S., Kim, K.-W., & Jung, S. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00026 · Cited by 316 · see citing works
Microglia in Alzheimer Disease: Well-Known Targets and New Opportunities
Hemonnot, A.-L., Hua, J., Ulmann, L., & Hirbec, H. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00233 · Cited by 298 · see citing works
Cho, S.-H., Chen, J. A., Sayed, F., Ward, M. E., Gao, F., Nguyen, T. A., Krabbe, G., Sohn, P. D., Lo, I., Minami, S., et al. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.2939-14.2015 · Cited by 275 · see citing works
Self-citationThe Impact of the CX3CL1/CX3CR1 Axis in Neurological Disorders
Pawelec, P., Ziemka‐Nałęcz, M., Sypecka, J., & Zalewska, T. (2020) · Cells · doi:10.3390/cells9102277 · Cited by 272 · see citing works
Microglia in CNS development: Shaping the brain for the future
Mosser, C., Baptista, S., Arnoux, I., & Audinat, É. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2017.01.002 · Cited by 268 · see citing works
Multiplex proteomics identifies novel CSF and plasma biomarkers of early Alzheimer’s disease
Whelan, C. D., Mattsson, N., Nagle, M. W., Vijayaraghavan, S., Hyde, C., Janelidze, S., Stomrud, E., Lee, J., Fitz, L., Samad, T. A., et al. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0795-2 · Cited by 262 · see citing works
Innate Immune Cell Death in Neuroinflammation and Alzheimer’s Disease
Rajesh, Y., & Kanneganti, T. (2022) · Cells · doi:10.3390/cells11121885 · Cited by 261 · see citing works
The Ischemic Environment Drives Microglia and Macrophage Function
Fumagalli, S., Perego, C., Pischiutta, F., Zanier, E. R., & Simoni, M. G. D. (2015) · Frontiers in Neurology · doi:10.3389/fneur.2015.00081 · Cited by 245 · see citing works
Current status of chemokines in the adult CNS
Goazigo, A. R.-L., Steenwinckel, J. V., Rostène, W. H., & Parsadaniantz, S. M. (2013) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.02.001 · Cited by 237 · see citing works
Microglia and mast cells: two tracks on the road to neuroinflammation
Skaper, S. D., Giusti, P., & Facci, L. (2012) · The FASEB Journal · doi:10.1096/fj.11-197194 · Cited by 235 · see citing works
Targeting Neuroinflammation to Treat Alzheimer’s Disease
Ardura-Fabregat, A., Boddeke, E., Boza‐Serrano, A., Brioschi, S., Castro‐Gomez, S., Ceyzériat, K., Dansokho, C., Dierkes, T., Gelders, G., Heneka, M. T., et al. (2017) · CNS Drugs · doi:10.1007/s40263-017-0483-3 · Cited by 236 · see citing works
Absence of CX3CR1 impairs the internalization of Tau by microglia
Bolós, M., Llorens-Martín, M., Perea, J. R., Jurado-Arjona, J., Rábano, A., Hernández, F., & Avila, J. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0200-1 · Cited by 231 · see citing works
Halloran, J. J., Hussong, S. A., Burbank, R. R., Podlutskaya, N., Fischer, K. E., Sloane, L. B., Austad, S. N., Strong, R., Richardson, A. G., Hart, M. J., et al. (2012) · Neuroscience · doi:10.1016/j.neuroscience.2012.06.054 · Cited by 221 · see citing works
Modulating neurotoxicity through CX3CL1/CX3CR1 signaling
Limatola, C., & Ransohoff, R. M. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00229 · Cited by 210 · see citing works
Self-citationZabel, M. K., Zhao, L., Zhang, Y., Gonzalez, S. R., Ma, W., Wang, X., Fariss, R. N., & Wong, W. T. (2016) · Glia · doi:10.1002/glia.23016 · Cited by 210 · see citing works
Old Maids: Aging and Its Impact on Microglia Function
Koellhoffer, E. C., McCullough, L. D., & Ritzel, R. M. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18040769 · Cited by 205 · see citing works
CX3CL1/CX3CR1 signaling targets for the treatment of neurodegenerative diseases
Subbarayan, M. S., Joly‐Amado, A., Bickford, P. C., & Nash, K. R. (2021) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.107989 · Cited by 204 · see citing works
Targeting microglia for the treatment of Alzheimer’s Disease
Wes, P. D., Sayed, F. A., Bard, F., & Gan, L. (2016) · Glia · doi:10.1002/glia.22988 · Cited by 185 · see citing works
Self-citationCX3CR1 deficiency induces an early protective inflammatory environment in ischemic mice
Fumagalli, S., Perego, C., Ortolano, F., & Simoni, M. G. D. (2013) · Glia · doi:10.1002/glia.22474 · Cited by 179 · see citing works
Neuroinflammation in Alzheimer's disease: chemokines produced by astrocytes and chemokine receptors.
(2014) · Europe PMC (PubMed Central) · Cited by 177 · see citing works
Tau Oligomers and Fibrils Induce Activation of Microglial Cells
Morales, I., Jiménez, J. M., Mancilla, M., & Maccioni, R. B. (2013) · Journal of Alzheimer’s Disease · doi:10.3233/jad-131843 · Cited by 160 · see citing works
Guruswamy, R., & ElAli, A. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18030496 · Cited by 159 · see citing works
Alzheimer’s Disease Pathogenesis: Role of Autophagy and Mitophagy Focusing in Microglia
Eshraghi, M., Adlimoghaddam, A., Mahmoodzadeh, A., Sharifzad, F., Yasavoli-Sharahi, H., Lorzadeh, S., Albensi, B. C., & Ghavami, S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22073330 · Cited by 158 · see citing works
Palmitoylethanolamide in CNS health and disease
Raso, G. M., Russo, R., Calignano, A., & Meli, R. (2014) · Pharmacological Research · doi:10.1016/j.phrs.2014.05.006 · Cited by 148 · see citing works
Microglial signalling mechanisms: Cathepsin S and Fractalkine
Clark, A. K., & Malcangio, M. (2011) · Experimental Neurology · doi:10.1016/j.expneurol.2011.09.012 · Cited by 149 · see citing works
Morari, J., Anhê, G. F., do Nascimento, L. F. R., de Moura, R. F., Razolli, D. S., Solon, C., Guadagnini, D., de Souza, G. F. P., Mattos, A. H. B., Tobar, N., et al. (2014) · Diabetes · doi:10.2337/db13-1495 · Cited by 147 · see citing works
Role of Neuroinflammation in Adult Neurogenesis and Alzheimer Disease: Therapeutic Approaches
Fuster-Matanzo, A., Llorens-Martı́n, M., Hernández, F., & Ávila, J. (2013) · Mediators of Inflammation · doi:10.1155/2013/260925 · Cited by 146 · see citing works
What is microglia neurotoxicity (Not)?
Biber, K. P. H., Owens, T., & Boddeke, E. (2014) · Glia · doi:10.1002/glia.22654 · Cited by 141 · see citing works
Functional and structural damage of neurons by innate immune mechanisms during neurodegeneration
Ising, C., & Heneka, M. T. (2018) · Cell Death and Disease · doi:10.1038/s41419-017-0153-x · Cited by 136 · see citing works
Neuroinflammation and fractalkine signaling in Alzheimer’s disease
Finneran, D. J., & Nash, K. R. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1412-9 · Cited by 133 · see citing works
Microglial Malfunction: The Third Rail in the Development of Alzheimer's Disease
Mhatre, S. D., Tsai, C. A., Rubin, A. J., James, M. L., & Andreasson, K. I. (2015) · Trends in Neurosciences · doi:10.1016/j.tins.2015.08.006 · Cited by 134 · see citing works
Fractalkine Signaling and Microglia Functions in the Developing Brain
Arnoux, I., & Audinat, É. (2015) · Neural Plasticity · doi:10.1155/2015/689404 · Cited by 125 · see citing works
Hu, X., Liou, A. K. F., Leak, R. K., Xu, M., An, C., Suenaga, J., Shi, Y., Gao, Y., Zheng, P., & Chen, J. (2014) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2014.06.002 · Cited by 131 · see citing works
Microglia in Alzheimer’s Disease: A Target for Therapeutic Intervention
Zhang, G., Wang, Z., Hu, H., Zhao, M., & Sun, L. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.749587 · Cited by 132 · see citing works
Donepezil inhibits the amyloid-beta oligomer-induced microglial activation in vitro and in vivo
Kim, H. G., Moon, M., Choi, J. G., Park, G., Kim, A., Hur, J., Lee, K., & Oh, M. S. (2013) · NeuroToxicology · doi:10.1016/j.neuro.2013.10.004 · Cited by 127 · see citing works
The brain’s best friend: microglial neurotoxicity revisited
Hellwig, S., Heinrich, A., & Biber, K. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00071 · Cited by 126 · see citing works
A microglia-cytokine axis to modulate synaptic connectivity and function
Werneburg, S., Feinberg, P. A., Johnson, K. M., & Schafer, D. P. (2017) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2017.10.002 · Cited by 121 · see citing works
Modulation of inflammation in transgenic models of Alzheimer’s disease
Birch, A. M., Katsouri, L., & Sastre, M. (2014) · Journal of Neuroinflammation · doi:10.1186/1742-2094-11-25 · Cited by 119 · see citing works
The role of innate immunity in Alzheimer's disease
Ennerfelt, H. E., & Lukens, J. R. (2020) · Immunological Reviews · doi:10.1111/imr.12896 · Cited by 121 · see citing works
Genetic targeting of microglia
Wieghofer, P., Knobeloch, K., & Prinz, M. (2014) · Glia · doi:10.1002/glia.22727 · Cited by 116 · see citing works
Skaper, S. D., & Facci, L. (2012) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2011.0391 · Cited by 118 · see citing works
Inhomogeneous distribution of Iba‐1 characterizes microglial pathology in Alzheimer's disease
Tischer, J., Krueger, M., Mueller, W. C., Staszewski, O., Prinz, M., Streit, W. J., & Bechmann, I. (2016) · Glia · doi:10.1002/glia.23024 · Cited by 117 · see citing works
Key Aging-Associated Alterations in Primary Microglia Response to Beta-Amyloid Stimulation
Caldeira, C., Cunha, C., Vaz, A. R., Falcão, A. S., Barateiro, A., Seixas, E., Fernandes, A., & Brites, D. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00277 · Cited by 117 · see citing works
Synaptic Elimination in Neurological Disorders
Cardozo, P. L., de Lima, I. B. Q., Maciel, E. M. A., Silva, N. C., Dobránsky, T., & Ribeiro, F. M. (2019) · Current Neuropharmacology · doi:10.2174/1570159x17666190603170511 · Cited by 113 · see citing works
Guedes, J. R., Lao, T., Cardoso, A. L., & El Khoury, J. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.00549 · Cited by 115 · see citing works
Microglia-Astrocyte Communication in Alzheimer’s Disease
Wu, Y., & Eisel, U. L. M. (2023) · Journal of Alzheimer s Disease · doi:10.3233/jad-230199 · Cited by 118 · see citing works
Fractalkine in the nervous system: neuroprotective or neurotoxic molecule?
Lauro, C., Catalano, M., Trettel, F., & Limatola, C. (2015) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12805 · Cited by 114 · see citing works
The role of microglia at synapses in the healthy CNS: novel insights from recent imaging studies
Tremblay, M. (2011) · Neuron Glia Biology · doi:10.1017/s1740925x12000038 · Cited by 109 · see citing works
Time-dependent effects of CX3CR1 in a mouse model of mild traumatic brain injury
Febinger, H. Y., Thomasy, H. E., Pavlova, M. N., Ringgold, K. M., Barf, P. R., George, A. M., Grillo, J. N., Bachstetter, A. D., Garcia, J. A., Cardona, A. E., et al. (2015) · Journal of Neuroinflammation · doi:10.1186/s12974-015-0386-5 · Cited by 110 · see citing works
“For instance, in a model of Alzheimer ’ s disease (AD), CX3CR1-deficient microglia from mice overexpressing hTau have increased hyperphosphorylated tau and more toxicity, as has been observed in other animal ’ s disease models [5, 17 – 20].”
Microglia and inflammation: conspiracy, controversy or control?
Fernandes, A. M. A., Miller‐Fleming, L., & Pais, T. F. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1670-8 · Cited by 110 · see citing works
Xu, H., Gelyana, E., Rajsombath, M., Yang, T., Li, S., & Selkoe, D. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.1023-16.2016 · Cited by 109 · see citing works
Liu, L. A., Kim, S., Buckley, M. T., Reyes, J. M., Kang, J., Tian, L., Wang, M., Lieu, A. C., Mao, M., Rodríguez-Mateo, C., et al. (2023) · Cell stem cell · doi:10.1016/j.stem.2023.03.016 · Cited by 110 · see citing works
G Protein-Coupled Receptors (GPCRs) in Alzheimer’s Disease: A Focus on BACE1 Related GPCRs
Zhao, J., Deng, Y., Jiang, Z., & Qing, H. (2016) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2016.00058 · Cited by 108 · see citing works
Poniatowski, Ł. A., Wojdasiewicz, P., Krawczyk, M., Szukiewicz, D., Gasik, R., Kubaszewski, Ł., & Kurkowska‐Jastrzębska, I. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-9787-4 · Cited by 102 · see citing works
Alzheimer’s Disease: Mechanism and Approach to Cell Therapy
Amemori, T., Jendelová, P., Růžička, J., Urdzíková, L. M., & Syková, E. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms161125961 · Cited by 102 · see citing works
Bettcher, B. M., Johnson, S. C., Fitch, R., Casaletto, K. B., Heffernan, K. S., Asthana, S., Zetterberg, H., Blennow, K., Carlsson, C. M., Neuhaus, J. M., et al. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-170602 · Cited by 103 · see citing works
Ahmed, N., Murakami, M., Hirose, Y., & Nakashima, M. (2016) · Stem Cells International · doi:10.1155/2016/8102478 · Cited by 96 · see citing works
Role of Atypical Chemokine Receptors in Microglial Activation and Polarization
Salvi, V., Sozio, F., Sozzani, S., & Prete, A. D. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00148 · Cited by 99 · see citing works
Afridi, R., Kim, J., Rahman, M. H., & Suk, K. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.00020 · Cited by 98 · see citing works
Thuc, O. L., Blondeau, N., Nahon, J., & Rovère, C. (2015) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12855 · Cited by 98 · see citing works
Chidambaram, H., Das, R. R., & Chinnathambi, S. (2020) · Cell & Bioscience · doi:10.1186/s13578-020-00474-4 · Cited by 97 · see citing works
Delpech, J.-C., Madore, C., Joffre, C., Aubert, A., Kang, J. X., Nadjar, A., & Layé, S. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.196 · Cited by 98 · see citing works
Role of Chemokines in the Development and Progression of Alzheimer’s Disease
Wojcieszak, J., Kuczyńska, K., & Zawilska, J. B. (2022) · Journal of Molecular Neuroscience · doi:10.1007/s12031-022-02047-1 · Cited by 97 · see citing works
From development to dysfunction: Microglia and the complement cascade in CNS homeostasis
Zabel, M. K., & Kirsch, W. M. (2013) · Ageing Research Reviews · doi:10.1016/j.arr.2013.02.001 · Cited by 95 · see citing works
Zanier, E. R., Marchesi, F., Ortolano, F., Perego, C., Arabian, M., Zoerle, T., Sammali, E., Pischiutta, F., & De Simoni, M.-G. (2016) · Journal of Neurotrauma · doi:10.1089/neu.2015.4041 · Cited by 94 · see citing works
Fractalkine Modulates Microglia Metabolism in Brain Ischemia
Lauro, C., Chece, G., Monaco, L., Antonangeli, F., Peruzzi, G., Rinaldo, S., Paone, A., Cutruzzolà, F., & Limatola, C. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00414 · Cited by 90 · see citing works
Cognitive Enhancers (Nootropics). Part 1: Drugs Interacting with Receptors
Froestl, W., Muhs, A., & Pfeifer, A. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-121186 · Cited by 91 · see citing works
Impaired Resolution of Inflammation in Alzheimer’s Disease: A Review
Whittington, R. A., Planel, E., & Terrando, N. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01464 · Cited by 89 · see citing works
Induction of Microglial Activation by Mediators Released from Mast Cells
Zhang, X., Wang, Y., Dong, H., Xu, Y. X., & Zhang, S. (2016) · Cellular Physiology and Biochemistry · doi:10.1159/000443093 · Cited by 90 · see citing works
Liu, W., Jiang, L., Bian, C., Liang, Y., Xing, R., Yishakea, M., & Dong, J. (2016) · Archivum Immunologiae et Therapiae Experimentalis · doi:10.1007/s00005-016-0395-9 · Cited by 88 · see citing works
Microglia communication: parallels between aging and Alzheimer's disease
Udeochu, J. C., Shea, J. M., & Villeda, S. A. (2016) · Clinical and Experimental Neuroimmunology · doi:10.1111/cen3.12307 · Cited by 87 · see citing works
Microglial NMDA receptors drive pro‐inflammatory responses via PARP‐1/TRMP2 signaling
Raghunatha, P., Vosoughi, A. R., Kauppinen, T. M., & Jackson, M. F. (2020) · Glia · doi:10.1002/glia.23790 · Cited by 87 · see citing works
Self-citationChemokine receptor CXCR2: Physiology regulator and neuroinflammation controller?
Veenstra, M., & Ransohoff, R. M. (2012) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2012.02.016 · Cited by 86 · see citing works
Self-citationGlial gene networks associated with alcohol dependence
Erickson, E. K., Blednov, Y. A., Harris, R. A., & Mayfield, R. D. (2019) · Scientific Reports · doi:10.1038/s41598-019-47454-4 · Cited by 83 · see citing works
Ishizuka, K., Fujita, Y., Kawabata, T., Kimura, H., Iwayama, Y., Inada, T., Okahisa, Y., Egawa, J., Usami, M., Kushima, I., et al. (2017) · Translational Psychiatry · doi:10.1038/tp.2017.173 · Cited by 82 · see citing works
Ferretti, E., Pistoia, V., & Corcione, A. (2014) · Mediators of Inflammation · doi:10.1155/2014/480941 · Cited by 82 · see citing works
The Evolving Biology of Microglia in Alzheimer's Disease
Malm, T. M., Jay, T. R., & Landreth, G. E. (2015) · Neurotherapeutics · doi:10.1007/s13311-014-0316-8 · Cited by 74 · see citing works
IVIg protects the 3xTg-AD mouse model of Alzheimer’s disease from memory deficit and Aβ pathology
St‐Amour, I., Paré, I., Tremblay, C., Coulombe, K., Bazin, R., & Calon, F. (2014) · Journal of Neuroinflammation · doi:10.1186/1742-2094-11-54 · Cited by 81 · see citing works
Cardona, S. M., Mendiola, A. S., Yang, Y.-C., Adkins, S. L., Torres, V., & Cardona, A. E. (2015) · ASN NEURO · doi:10.1177/1759091415608204 · Cited by 81 · see citing works
Hickman, S. E., Allison, E. K., Coleman, U., Kingery-Gallagher, N. D., & El Khoury, J. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02780 · Cited by 80 · see citing works
Pardo, C. A., Farmer, C., Thurm, A. E., Shebl, F. M., Ilieva, J., Kalra, S., & Swedo, S. E. (2017) · Molecular Autism · doi:10.1186/s13229-016-0115-7 · Cited by 80 · see citing works
Physical Exercise-Induced Myokines in Neurodegenerative Diseases
Lee, B., Shin, M., Park, Y., Won, S.-Y., & Cho, K. S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115795 · Cited by 79 · see citing works
Microglia as a critical player in both developmental and late-life CNS pathologies
Derecki, N. C., Katzmarski, N., Kipnis, J., & Meyer-Luehmann, M. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1321-z · Cited by 61 · see citing works
Castro-Sánchez, S., García-Yagüe, Á. J., Kügler, S., & Lastres-Becker, I. (2019) · Redox Biology · doi:10.1016/j.redox.2019.101118 · Cited by 76 · see citing works
Zhou, F., Sun, Y., Xie, X., & Zhao, Y. (2023) · Alzheimer s Research & Therapy · doi:10.1186/s13195-023-01254-1 · Cited by 75 · see citing works
Luo, T., Wu, J., Kabadi, S. V., Sabirzhanov, B. E., Guanciale, K., Hanscom, M., Faden, J., Cardiff, K., Bengson, C. J., & Faden, A. I. (2013) · Anesthesiology · doi:10.1097/aln.0000000000000020 · Cited by 75 · see citing works
Neuroinflammatory Signaling in the Pathogenesis of Alzheimer’s Disease
Uddin, M. S., Kabir, M. T., Jalouli, M., Rahman, M. A., Jeandet, P., Behl, T., Alexiou, A. T., Albadrani, G. M., Abdel‐Daim, M. M., Perveen, A., et al. (2021) · Current Neuropharmacology · doi:10.2174/1570159x19666210826130210 · Cited by 76 · see citing works
AmeliMojarad, M., & AmeliMojarad, M. (2024) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.14856 · Cited by 73 · see citing works
The Role of Inflammatory Mediators in the Pathogenesis of Alzheimer’s Disease
Azizi, G., Navabi, S. S., Al-Shukaili, A. K., Seyedzadeh, M. H., Yazdani, R., & Mirshafiey, A. (2015) · Sultan Qaboos University medical journal · doi:10.18295/squmj.2015.15.03.002 · Cited by 72 · see citing works
Microglia Ontology and Signaling
ElAli, A., & Rivest, S. (2016) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2016.00072 · Cited by 73 · see citing works
- Authors
- Cho, S.-H., Sun, B., Zhou, Y., Kauppinen, T. M., Halabisky, B., Wes, P., Ransohoff, R. M., & Gan, L.
- Affiliations
- Gladstone Institutes (US)
- University of California, San Francisco (US)
- Bristol-Myers Squibb (United States) (US)
- Cleveland Clinic (US)
- Corresponding author
- Gan, Li
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2011-09
- Volume
- 286
- Issue
- 37
- Pages
- 32713-32722
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3173153
- OpenAlex
- W2148721608
- Cited by
- 268
- References
- 52
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 14 · 2023: 20 · 2022: 15 · 2021: 14 · 2020: 16 · 2019: 20 · 2018: 18 · 2017: 17 · 2016: 18 · 2015: 28 · 2014: 27 · 2013: 22 · 2012: 14
- FWCI
- 11.85
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1c06rr018928-01)
- University of California, San Diego
- National Institute on Aging (R01AG030207)
- National Cancer Institute (CO6 RRO18928)
- National Institute of Neurological Disorders and Stroke (P30NS065780)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- CX3CR1, microglial activation, Alzheimer's disease, cognitive impairment, amyloid precursor protein, tau pathology, calbindin, dentate gyrus, neuroinflammation, interleukin-6, TNF-α, memory impairment, novel object recognition, passive avoidance
- MeSH terms
- CX3C Chemokine Receptor 1, Alzheimer Disease, Animals, Cognition Disorders, Disease Models, Animal, Humans, Nerve Tissue Proteins, Signal Transduction, Cytokines, Amyloid beta-Protein Precursor, Microglia, Mice, Knockout, Dentate Gyrus, Receptors, Chemokine, Mice, Calbindins, S100 Calcium Binding Protein G
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