Interleukin-34 Selectively Enhances the Neuroprotective Effects of Microglia to Attenuate Oligomeric Amyloid-β Neurotoxicity
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Microglia, macrophage-like resident immune cells in the brain, possess both neurotoxic and neuroprotective properties and have a critical role in the development of Alzheimer's disease (AD). We examined the function of Interleukin-34 (IL-34), a newly discovered cytokine, on microglia because it reportedly induces proliferation of monocytes and macrophages. We observed that the neuronal cells primarily produce IL-34 and that microglia express its receptor, colony-stimulating factor 1 receptor. IL-34 promoted microglial proliferation and clearance of soluble oligomeric amyloid-β (oAβ), which mediates synaptic dysfunction and neuronal damage in AD. IL-34 increased the expression of insulin-degrading enzyme, aiding the clearance of oAβ, and induced the antioxidant enzyme heme oxygenase-1 in microglia to reduce oxidative stress, without producing neurotoxic molecules. Consequently, microglia treated with IL-34 attenuated oAβ neurotoxicity in primary neuron-microglia co-cultures. In vivo, intracerebroventricular administration of IL-34 ameliorated impairment of associative learning and reduced oAβ levels through up-regulation of insulin-degrading enzyme and heme oxygenase-1 in an APP/PS1 transgenic mouse model of AD. These findings support the idea that enhancement of the neuroprotective property of microglia by IL-34 may be an effective approach against oAβ neurotoxicity in AD.
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Interleukins such as IL-18, IL-34, IL-4, IL-10, IL-13, and others have been reported as either up- or downregulated in patient brain tissue, CSF or blood in AD and related tauopathies.
“Interleukins such as IL-18, IL-34, IL-4, IL-10 IL-13, and others have been reported as either up or downregulated in patient brain tissue, CSF or blood [92, 103, 167].”
From Glial contributions to neurodegeneration in tauopathies (2017) · cites this paper as [167]
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1 retracted
RETRACTED ARTICLE: A specific amyloid-β protein assembly in the brain impairs memory
Lesné, S., Koh, M. T., Kotilinek, L., Kayed, R., Glabe, C. G., Yang, A., Gallagher, M., & Ashe, K. H. (2006) · Nature · doi:10.1038/nature04533 · Cited by 2,769 · see citing works
RetractedThe Mouse Brain in Stereotaxic Coordinates
Paxinos, G. (2001) · Cited by 12,859 · see citing works
Alzheimer's Disease Is a Synaptic Failure
Selkoe, D. J. (2002) · Science · doi:10.1126/science.1074069 · Cited by 4,420 · see citing works
Walsh, D. M., Klyubin, I., Fadeeva, J. V., Cullen, W. K., Anwyl, R., Wolfe, M. S., Rowan, M. J., & Selkoe, D. J. (2002) · Nature · doi:10.1038/416535a · Cited by 4,291 · see citing works
mouse brain in stereotaxic coordinates
Franklin, K. B. J., & Paxinos, G. (1997) · Cited by 3,258 · see citing works
THE HEME OXYGENASE SYSTEM:A Regulator of Second Messenger Gases
Maines, M. D. (1997) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.37.1.517 · Cited by 2,489 · see citing works
Shankar, G. M., Bloodgood, B. L., Townsend, M., Walsh, D. M., Selkoe, D. J., & Sabatini, B. L. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.4970-06.2007 · Cited by 1,592 · see citing works
Oligomeric and fibrillar species of amyloid-β peptides differentially affect neuronal viability
Dahlgren, K. N., Manelli, A. M., Stine, W. B., Baker, L. K., Krafft, G. A., & LaDu, M. J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m201750200 · Cited by 1,452 · see citing works
Activation of microglial cells by β-amyloid protein and interferon-γ
Meda, L., Cassatella, M. A., Szendrei, G. I., Otvos, L., Baron, P., Villalba, M., Ferrari, D., & Rossi, F. (1995) · Nature · doi:10.1038/374647a0 · Cited by 1,314 · see citing works
Demuro, A., Mina, E. W., Kayed, R., Milton, S. C. F., Parker, I., & Glabe, C. G. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m500997200 · Cited by 1,038 · see citing works
Rapid appearance and local toxicity of amyloid-β plaques in a mouse model of Alzheimer’s disease
Meyer-Luehmann, M., Spires-Jones, T. L., Prada, C., Garcia-Alloza, M., de Calignon, A., Rozkalne, A., Koenigsknecht-Talboo, J., Holtzman, D. M., Bacskai, B. J., & Hyman, B. T. (2008) · Nature · doi:10.1038/nature06616 · Cited by 987 · see citing works
Pollock, J. S., Förstermann, U., Mitchell, J. A., Warner, T. D., Schmidt, H. H. H. W., Nakane, M., & Murad, F. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.23.10480 · Cited by 979 · see citing works
Li, S., Hong, S., Shepardson, N. E., Walsh, D. M., Shankar, G. M., & Selkoe, D. (2009) · Neuron · doi:10.1016/j.neuron.2009.05.012 · Cited by 972 · see citing works
De Felice, F. G., Velasco, P. T., Lambert, M. P., Viola, K., Fernandez, S. J., Ferreira, S. T., & Klein, W. L. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m607483200 · Cited by 882 · see citing works
Discovery of a Cytokine and Its Receptor by Functional Screening of the Extracellular Proteome
Lin, H., Lee, E., Hestir, K., Leo, C., Huang, M., Bosch, E., Halenbeck, R., Wu, G., Zhou, A. J., Behrens, D., et al. (2008) · Science · doi:10.1126/science.1154370 · Cited by 815 · see citing works
Neuronal ‘On’ and ‘Off’ signals control microglia
Biber, K., Neumann, H., Inoue, K., & Boddeke, H. W. G. M. (2007) · Trends in Neurosciences · doi:10.1016/j.tins.2007.08.007 · Cited by 787 · see citing works
Leissring, M. A., Farris, W., Chang, A. Y., Walsh, D. M., Wu, X., Sun, X., Frosch, M. P., & Selkoe, D. J. (2003) · Neuron · doi:10.1016/s0896-6273(03)00787-6 · Cited by 708 · see citing works
Role of toll-like receptor signalling in A uptake and clearance
Tahara, K., Kim, H.-D., Jin, J.-J., Maxwell, J. A., Li, L., & Fukuchi, K.-I. (2006) · Brain · doi:10.1093/brain/awl249 · Cited by 493 · see citing works
Inflammation, autotoxicity and Alzheimer disease
McGeer, P. L. (2001) · Neurobiology of Aging · doi:10.1016/s0197-4580(01)00289-5 · Cited by 474 · see citing works
Microglia Mediate the Clearance of Soluble Aβ through Fluid Phase Macropinocytosis
Mandrekar, S., Jiang, Q., Lee, C. Y. D., Koenigsknecht-Talboo, J., Holtzman, D. M., & Landreth, G. E. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.5572-08.2009 · Cited by 415 · see citing works
Matrix Metalloproteinase-9 Degrades Amyloid-β Fibrils in Vitro and Compact Plaques in Situ
Yan, P., Hu, X., Song, H., Yin, K., Bateman, R. J., Cirrito, J. R., Xiao, Q., Hsu, F. F., Turk, J. W., Xu, J., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m602440200 · Cited by 380 · see citing works
Wei, S., Nandi, S., Chitu, V., Yeung, Y.-G., Yu, W., Huang, M., Williams, L. T., Lin, H., & Stanley, E. R. (2010) · Journal of Leukocyte Biology · doi:10.1189/jlb.1209822 · Cited by 370 · see citing works
Suzumura, A., Mezitis, S., Gonatas, N., & Silberberg, D. (1987) · Journal of Neuroimmunology · doi:10.1016/0165-5728(87)90121-4 · Cited by 349 · see citing works
Self-citationTakeuchi, H., Mizuno, T., Zhang, G., Wang, J., Kawanokuchi, J., Kuno, R., & Suzumura, A. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m413863200 · Cited by 285 · cited 1× · see citing works
“, Chiba, Japan) was used, as described previously.(14)”
Self-citationActivation of Microglia Acidifies Lysosomes and Leads to Degradation of Alzheimer Amyloid Fibrils
Majumdar, A., Cruz, D., Asamoah, N., Buxbaum, A., Sohar, I., Lobel, P., & Maxfield, F. R. (2007) · Molecular Biology of the Cell · doi:10.1091/mbc.e06-10-0975 · Cited by 271 · see citing works
Richard, K. L., Filali, M., Préfontaine, P., & Rivest, S. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.1146-08.2008 · Cited by 261 · see citing works
Chihara, T., Suzu, S., Hassan, R., Chutiwitoonchai, N., Hiyoshi, M., Motoyoshi, K., Kimura, F., & Okada, S. (2010) · Cell Death and Differentiation · doi:10.1038/cdd.2010.60 · Cited by 231 · see citing works
Mizuno, T., Kurotani, T., Komatsu, Y., Kawanokuchi, J., Kato, H., Mitsuma, N., & Suzumura, A. (2003) · Neuropharmacology · doi:10.1016/j.neuropharm.2003.09.009 · Cited by 226 · see citing works
Self-citationBoissonneault, V., Filali, M., Lessard, M., Relton, J., Wong, G., & Rivest, S. (2008) · Brain · doi:10.1093/brain/awn331 · Cited by 221 · see citing works
Chen, K., Iribarren, P., Hu, J., Chen, J., Gong, W., Cho, E. H., Lockett, S., Dunlop, N. M., & Wang, J. M. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m508125200 · Cited by 214 · see citing works
Heme oxygenase-1, a critical arbitrator of cell death pathways in lung injury and disease
Morse, D., Lin, L., Choi, A. M. K., & Ryter, S. W. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.04.007 · Cited by 182 · see citing works
Scholtzova, H., Kascsak, R. J., Bates, K. A., Boutajangout, A., Kerr, D. J., Meeker, H. C., Mehta, P. D., Spinner, D. S., & Wisniewski, T. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.5715-08.2009 · Cited by 166 · see citing works
Baud’huin, M., Renault, R., Charrier, C., Riet, A., Moreau, A., Brion, R., Gouin, F., Duplomb, L., & Heymann, D. (2010) · The Journal of Pathology · doi:10.1002/path.2684 · Cited by 160 · see citing works
Mouri, A., Noda, Y., Hara, H., Mizoguchi, H., Tabira, T., & Nabeshima, T. (2007) · The FASEB Journal · doi:10.1096/fj.06-7685com · Cited by 144 · see citing works
Self-citationDoi, Y., Mizuno, T., Maki, Y., Jin, S., Mizoguchi, H., Ikeyama, M., Doi, M., Michikawa, M., Takeuchi, H., & Suzumura, A. (2009) · The American Journal of Pathology · doi:10.2353/ajpath.2009.090418 · Cited by 135 · see citing works
Self-citationZhao, Z., Xiang, Z., Haroutunian, V. H., Buxbaum, J. D., Stetka, B., & Pasinetti, G. M. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2006.05.001 · Cited by 122 · see citing works
Mizoguchi, H., Yamada, K., Mouri, A., Niwa, M., Mizuno, T., Noda, Y., Nitta, A., Itohara, S., Banno, Y., & Nabeshima, T. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04623.x · Cited by 71 · see citing works
Self-citationBaud’huin, M., Renault, R., Charrier, C., Riet, A. V., Brion, R., Moreau, A., Gouin, F., Duplomb, L., & Heymann, D. (2010) · Bone · doi:10.1016/j.bone.2010.04.314 · Cited by 40 · see citing works
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Sorted by citations
Cytokine networks in neuroinflammation
Becher, B., Spath, S., & Goverman, J. M. (2016) · Nature reviews. Immunology · doi:10.1038/nri.2016.123 · Cited by 681 · see citing works
Greter, M., Lelios, I., Pelczar, P., Hoeffel, G., Price, J., Leboeuf, M., Kündig, T. M., Frei, K., Ginhoux, F., Merad, M., et al. (2012) · Immunity · doi:10.1016/j.immuni.2012.11.001 · Cited by 630 · see citing works
Glial contributions to neurodegeneration in tauopathies
Leyns, C. E. G., & Holtzman, D. M. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0192-x · Cited by 409 · see citing works
Regulation of Microglial Proliferation during Chronic Neurodegeneration
Gómez-Nicola, D., Fransen, N. L., Suzzi, S., & Perry, V. H. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.4440-12.2013 · Cited by 407 · see citing works
Emerging Roles for CSF-1 Receptor and its Ligands in the Nervous System
Chiţu, V., Gökhan, Ş., Nandi, S., Mehler, M. F., & Stanley, E. R. (2016) · Trends in Neurosciences · doi:10.1016/j.tins.2016.03.005 · Cited by 354 · see citing works
TREM2 regulates microglial cell activation in response to demyelination in vivo
Cantoni, C., Bollman, B., Licastro, D., Xie, M., Mikesell, R., Schmidt, R., Yuede, C. M., Galimberti, D., Olivecrona, G., Klein, R. S., et al. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1388-1 · Cited by 296 · see citing works
Microglia actions in Alzheimer's disease
Prokop, S., Miller, K. R., & Heppner, F. L. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1182-x · Cited by 291 · see citing works
Luo, J., Elwood, F., Britschgi, M., Villeda, S., Zhang, H., Ding, Z., Zhu, L., Alabsi, H., Getachew, R., Narasimhan, R., et al. (2013) · Journal of Experimental Medicine · doi:10.1084/jem.20120412 · Cited by 262 · see citing works
Microglia in the developing brain: a potential target with lifetime effects
Harry, G. J., & Kraft, A. D. (2012) · NeuroToxicology · doi:10.1016/j.neuro.2012.01.012 · Cited by 250 · see citing works
Parajuli, B., Sonobe, Y., Horiuchi, H., Takeuchi, H., Mizuno, T., & Suzumura, A. (2013) · Cell Death & Disease · doi:10.1038/cddis.2013.503 · Cited by 232 · see citing works
Self-citationSvoboda, D. S., Barrasa, M. I., Shu, J., Rietjens, R. G. J., Zhang, S., Mitalipova, M., Berube, P., Fu, D., Shultz, L. D., Bell, G. W., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1913541116 · Cited by 203 · see citing works
Tijms, B. M., Vromen, E. M., Mjaavatten, O., Holstege, H. H., Reus, L. M., van der Lee, S. J., Wesenhagen, K. E. J., Lorenzini, L., Vermunt, L., Venkatraghavan, V., et al. (2024) · Nature Aging · doi:10.1038/s43587-023-00550-7 · Cited by 222 · see citing works
Suicide and Microglia: Recent Findings and Future Perspectives Based on Human Studies
Suzuki, H., Ohgidani, M., Kuwano, N., Chrétien, F., Lorin de la Grandmaison, G., Onaya, M., Tominaga, I., Setoyama, D., Kang, D., Mimura, M., et al. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00031 · Cited by 198 · see citing works
Targeting neuroinflammation in Alzheimer’s disease: from mechanisms to clinical applications
Si, Z.-Z., Zou, C.-J., Mei, X., Mei, X., Luo, H., Shen, Y., Hu, J., Li, X.-X., Wu, L., & Liu, Y. (2022) · Neural Regeneration Research · doi:10.4103/1673-5374.353484 · Cited by 192 · see citing works
Foucher, E. D., Blanchard, S., Preisser, L., Garo, E., Ifrah, N., Guardiola, P., Delneste, Y., & Jeannin, P. (2013) · PLoS ONE · doi:10.1371/journal.pone.0056045 · Cited by 177 · see citing works
Structural Basis for the Dual Recognition of Helical Cytokines IL-34 and CSF-1 by CSF-1R
Ma, X., Lin, W., Chen, Y., Stawicki, S. S., Mukhyala, K., Wu, Y. R., Martin, F., Bazán, J. F., & Starovasnik, M. A. (2012) · Structure · doi:10.1016/j.str.2012.02.010 · Cited by 174 · see citing works
CCL11 enhances excitotoxic neuronal death by producing reactive oxygen species in microglia
Parajuli, B., Horiuchi, H., Mizuno, T., Takeuchi, H., & Suzumura, A. (2015) · Glia · doi:10.1002/glia.22892 · Cited by 160 · see citing works
Self-citationThe twin cytokines interleukin-34 and CSF-1: masterful conductors of macrophage homeostasis
Muñoz-García, J., Cochonneau, D., Télétchéa, S., Moranton, E., Lanoé, D., Brion, R., Lézot, F., Heymann, M., & Heymann, D. (2020) · Theranostics · doi:10.7150/thno.50683 · Cited by 155 · see citing works
Parajuli, B., Sonobe, Y., Kawanokuchi, J., Doi, Y., Noda, M., Takeuchi, H., Mizuno, T., & Suzumura, A. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-268 · Cited by 159 · see citing works
Self-citationInterleukin-34, a comprehensive review
Baghdadi, M., Umeyama, Y., Hama, N., Kobayashi, T., Han, N., Wada, H., & Seino, K.-I. (2018) · Journal of Leukocyte Biology · doi:10.1002/jlb.mr1117-457r · Cited by 145 · see citing works
Molecular Mechanisms of Microglial Motility: Changes in Ageing and Alzheimer’s Disease
Franco-Bocanegra, D. K., McAuley, C., Nicoll, J. A. R., & Boche, D. (2019) · Cells · doi:10.3390/cells8060639 · Cited by 147 · see citing works
Regulation of microglia development and homeostasis.
Greter, M., & Merad, M. (2013) · Glia · doi:10.1002/glia.22408 · Cited by 141 · 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
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
Targeting CSF-1R represents an effective strategy in modulating inflammatory diseases
Xiang, C., Li, H., & Tang, W. (2022) · Pharmacological Research · doi:10.1016/j.phrs.2022.106566 · Cited by 114 · see citing works
Immunoregulatory properties of the cytokine IL-34
Guillonneau, C., Bézie, S., & Anegon, I. (2017) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-017-2482-4 · Cited by 112 · see citing works
Western, D., Timsina, J., Wang, L., Wang, C., Yang, C., Phillips, B., Wang, Y., Liu, M., Ali, M., Beric, A., et al. (2024) · Nature Genetics · doi:10.1038/s41588-024-01972-8 · Cited by 111 · see citing works
Immunity and inflammation in neurodegenerative diseases.
Cappellano, G., Carecchio, M., Fleetwood, T., Magistrelli, L., Cantello, R. M., Dianzani, U., & Comi, C. (2013) · Europe PMC (PubMed Central) · Cited by 105 · see citing works
Emerging roles of IL-34 in health and disease
Lelios, I., Cansever, D., Utz, S. G., Mildenberger, W., Stifter, S. A., & Greter, M. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20190290 · Cited by 101 · see citing works
Doi, Y., Takeuchi, H., Horiuchi, H., Hanyu, T., Kawanokuchi, J., Jin, S., Parajuli, B., Sonobe, Y., Mizuno, T., & Suzumura, A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0061988 · Cited by 102 · see citing works
Self-citationIL-34 Is Associated with Obesity, Chronic Inflammation, and Insulin Resistance
Chang, E., Lee, S. K., Song, Y. S., Jang, Y. J., Park, H. S., Hong, J. P., Ko, A., Kim, D. Y., Kim, J.-H., Lee, Y. J., et al. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-4409 · Cited by 101 · see citing works
Fukumoto, K., Mizoguchi, H., Takeuchi, H., Horiuchi, H., Kawanokuchi, J., Jin, S., Mizuno, T., & Suzumura, A. (2014) · Behavioural Brain Research · doi:10.1016/j.bbr.2014.03.046 · Cited by 99 · see citing works
Self-citationWalker, D. G., Tang, T. M., & Lue, L. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00244 · Cited by 93 · see citing works
Wang, Y., & Colonna, M. (2014) · European Journal of Immunology · doi:10.1002/eji.201344365 · Cited by 97 · see citing works
Macrophages: Subtypes, Distribution, Polarization, Immunomodulatory Functions, and Therapeutics
Peng, M., Li, N., Wang, H., Li, Y., Liu, H., Luo, Y., Lang, B., Zhang, W., Li, S., Tian, L., et al. (2025) · MedComm · doi:10.1002/mco2.70304 · Cited by 95 · see citing works
Jha, N. K., Jha, S., Kumar, D., Kejriwal, N., Sharma, R., Ambasta, R. K., & Kumar, P. (2015) · Journal of Alzheimer's Disease · doi:10.3233/jad-150379 · Cited by 79 · see citing works
Wang, T., Kono, T., Monte, M. M., Kuse, H., Costa, M. M., Korenaga, H., Maehr, T., Husain, M., Sakai, M., & Secombes, C. J. (2012) · Molecular Immunology · doi:10.1016/j.molimm.2012.09.008 · Cited by 82 · see citing works
CSF1R Stimulation Promotes Increased Neuroprotection by CD11c+ Microglia in EAE
Wlodarczyk, A., Benmamar-Badel, A., Cédile, O., Jensen, K. N., Kramer, I., Elsborg, N. B., & Owens, T. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00523 · Cited by 81 · see citing works
Help-me signaling: Non-cell autonomous mechanisms of neuroprotection and neurorecovery
Xing, C., & Lo, E. H. (2016) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2016.04.004 · Cited by 75 · see citing works
Rivera-Escalera, F., Pinney, J. J., Owlett, L., Ahmed, H., Thakar, J., Olschowka, J. A., Elliott, M. R., & O’Banion, M. K. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1645-7 · Cited by 75 · see citing works
“In fact, several studies have shown increased microglial proliferation associated with enhanced amyloid plaque clearance [26, 71, 72, 75].”
Interleukin 34, from pathogenesis to clinical applications
Baghdadi, M., Endo, H., Tanaka, Y., Wada, H., & Seino, K. (2017) · Cytokine · doi:10.1016/j.cyto.2017.08.020 · Cited by 73 · see citing works
Azizi, G., & Mirshafiey, A. (2012) · Immunopharmacology and Immunotoxicology · doi:10.3109/08923973.2012.705292 · Cited by 72 · see citing works
Innate Immunity in Alzheimer’s Disease: A Complex Affair
Guillot‐Sestier, M., & Town, T. (2013) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527311312050008 · Cited by 71 · see citing works
Félix, J., Elegheert, J., Gutsche, I., Shkumatov, A. V., Wen, Y., Bracke, N., Pannecoucke, E., Vandenberghe, I. H. M., Devreese, B. V., Svergun, D. I., et al. (2013) · Structure · doi:10.1016/j.str.2013.01.018 · Cited by 71 · see citing works
Peña‐Altamira, E., Prati, F., Massenzio, F., Virgili, M., Contestabile, A., Bolognesi, M. L., & Monti, B. (2015) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2016.1121237 · Cited by 70 · see citing works
Kuwano, N., Kato, T. A., Mitsuhashi, M., Sato‐Kasai, M., Shimokawa, N., Hayakawa, K., Ohgidani, M., Sagata, N., Kubo, H., Sakurai, T., et al. (2018) · Journal of Affective Disorders · doi:10.1016/j.jad.2018.07.040 · Cited by 69 · see citing works
The Biphasic Role of Microglia in Alzheimer's Disease
Mizuno, T. (2012) · International Journal of Alzheimer s Disease · doi:10.1155/2012/737846 · Cited by 67 · see citing works
Self-citationInsulin‐degrading enzyme: an ally against metabolic and neurodegenerative diseases
Sousa, L., Guarda, M., Meneses, M. J., Macedo, M. P., & Miranda, H. V. (2021) · The Journal of Pathology · doi:10.1002/path.5777 · Cited by 63 · see citing works
Exploring glia to better understand Alzheimer’s disease
Kim, Y. S., Jung, H. M., & Yoon, B. (2018) · Animal Cells and Systems · doi:10.1080/19768354.2018.1508498 · Cited by 65 · see citing works
Jin, S., Sonobe, Y., Kawanokuchi, J., Horiuchi, H., Cheng, Y. H., Wang, Y., Mizuno, T., Takeuchi, H., & Suzumura, A. (2014) · PLoS ONE · doi:10.1371/journal.pone.0115981 · Cited by 63 · see citing works
Self-citationFunctions of interleukin‐34 and its emerging association with rheumatoid arthritis
Zhou, R., Wu, X., Xie, Y., Dai, B., Hu, W. M., Ge, J., & Chen, F. (2016) · Immunology · doi:10.1111/imm.12660 · Cited by 62 · see citing works
The Role of Microglia in Prion Diseases: A Paradigm of Functional Diversity
Obst, J., Simon, E., Mancuso, R., & Gómez‐Nicola, D. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00207 · Cited by 59 · see citing works
Clinically Precedented Protein Kinases: Rationale for Their Use in Neurodegenerative Disease
Benn, C., & Dawson, L. A. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.00242 · Cited by 57 · see citing works
IL-34 and CSF-1, deciphering similarities and differences at steady state and in diseases
Freuchet, A., Salama, A., Remy, S., Guillonneau, C., & Anegón, I. (2021) · Journal of Leukocyte Biology · doi:10.1002/jlb.3ru1120-773r · Cited by 54 · see citing works
Regulation of microglia population dynamics throughout development, health, and disease
Hammond, B. P., Manek, R., Kerr, B. J., Macauley, M. S., & Plemel, J. R. (2021) · Glia · doi:10.1002/glia.24047 · Cited by 56 · see citing works
The role of microglia in Alzheimer's disease and progress of treatment
Guan, Y.-H., Zhang, L.-W., Wang, S.-Y., Deng, Y.-D., Zhou, H.-S., Chen, D., & Zhang, L. (2022) · Ibrain · doi:10.1002/ibra.12023 · Cited by 48 · see citing works
Sassi, C., Nalls, M. A., Ridge, P. G., Gibbs, J. R., Lupton, M. K., Troakes, C., Lunnon, K., Al‐Sarraj, S., Brown, K. S., Medway, C., et al. (2018) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2018.01.015 · Cited by 50 · see citing works
Imai, K., Kotani, T., Tsuda, H., Mano, Y., Nakano, T., Ushida, T., Li, H., Miki, R., Sumigama, S., Iwase, A., et al. (2016) · Free Radical Biology & Medicine · doi:10.1016/j.freeradbiomed.2015.12.015 · Cited by 44 · see citing works
Self-citationAcosta, S., Tajiri, N., Sanberg, P., Kaneko, Y., & Borlongan, C. (2016) · Journal of Cellular Physiology · doi:10.1002/jcp.25629 · Cited by 49 · see citing works
The Functions and Phenotypes of Microglia in Alzheimer’s Disease
Fujikawa, R., & Tsuda, M. (2023) · Cells · doi:10.3390/cells12081207 · Cited by 55 · see citing works
Chu, C., Wang, S., Li, C.-L., Chen, S., Hu, C.-F., Chung, Y.-L., Chen, S., Wang, Q., Lu, R., Gao, H., et al. (2016) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2016.04.015 · Cited by 48 · see citing works
Sweepers in the CNS: Microglial Migration and Phagocytosis in the Alzheimer Disease Pathogenesis
Noda, M., & Suzumura, A. (2012) · International Journal of Alzheimer s Disease · doi:10.1155/2012/891087 · Cited by 47 · see citing works
Self-citationTian, L., Hui, C. W., Bisht, K., Tan, Y., Sharma, K. P., Chen, S., Zhang, X., & Tremblay, M. (2017) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2017.01.007 · Cited by 47 · see citing works
Ge, Y., Huang, M., & Yao, Y.-M. (2019) · International Journal of Biological Sciences · doi:10.7150/ijbs.35070 · Cited by 46 · see citing works
Ma, D., Doi, Y., Jin, S., Li, E., Sonobe, Y., Takeuchi, H., Mizuno, T., & Suzumura, A. (2012) · Neuroscience Letters · doi:10.1016/j.neulet.2012.08.071 · Cited by 45 · see citing works
Self-citationPons, V., Lévesque, P., Plante, M.-M., & Rivest, S. (2021) · Alzheimer s Research & Therapy · doi:10.1186/s13195-020-00747-7 · Cited by 43 · see citing works
Takata, K., Ginhoux, F., & Shimohama, S. (2021) · Biochemical Pharmacology · doi:10.1016/j.bcp.2021.114754 · Cited by 40 · see citing works
Li, Y., Li, Y., & Zhu, Z. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1284214 · Cited by 41 · see citing works
Targeting Systemic Innate Immune Cells as a Therapeutic Avenue for Alzheimer Disease
Pons, V., & Rivest, S. (2022) · Pharmacological Reviews · doi:10.1124/pharmrev.121.000400 · Cited by 39 · see citing works
Basic Concept of Microglia Biology and Neuroinflammation in Relation to Psychiatry
Mattei, D., & Notter, T. (2019) · Current topics in behavioral neurosciences · doi:10.1007/7854_2018_83 · Cited by 37 · see citing works
Ardura-Fabregat, A., Bosch, L. F. P., Wogram, E., Mossad, O., Sankowski, R., Aktories, P., Kieger, L., Cook, J., Hasavci, D., Ulupinar, H., et al. (2025) · Nature Neuroscience · doi:10.1038/s41593-025-02006-0 · Cited by 42 · see citing works
Veremeyko, T., Yung, A. W. Y., Dukhinova, M., Strekalova, T. V., & Ponomarev, E. D. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00453 · Cited by 34 · see citing works
Swiatkowski, P., Nikolaeva, I., Kumar, G., Zucco, A. J., Akum, B. F., Patel, M. V., D’Arcangelo, G., & Firestein, B. L. (2017) · Scientific Reports · doi:10.1038/s41598-017-01826-w · Cited by 33 · see citing works
miR‑155 mediates inflammatory injury of hippocampal neuronal cells via the activation of microglia
Sun, X., Song, M.-F., Song, H., Wang, Y., Luo, M., & Yin, L. (2019) · Molecular Medicine Reports · doi:10.3892/mmr.2019.9917 · Cited by 32 · see citing works
Genetic Variability in Molecular Pathways Implicated in Alzheimer's Disease: A Comprehensive Review
Vogrinc, D., Goričar, K., & Dolžan, V. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.646901 · Cited by 32 · see citing works
Exposure to 1-bromopropane induces microglial changes and oxidative stress in the rat cerebellum
Subramanian, K., Mohideen, S. S., Suzumura, A., Asai, N., Murakumo, Y., Takahashi, M., Jin, S., Zhang, L., Huang, Z., Ichihara, S., et al. (2012) · Toxicology · doi:10.1016/j.tox.2012.07.006 · Cited by 32 · see citing works
Self-citationChristensen, D. P., Ejlerskov, P., Rasmussen, I., & Vilhardt, F. (2016) · Journal of Neuroinflammation · doi:10.1186/s12974-016-0519-5 · Cited by 31 · see citing works
Zuroff, L., Torbati, T., Hart, N. J., Fuchs, D., Sheyn, J., Rentsendorj, A., Koronyo, Y., Hayden, E. Y., Teplow, D., Black, K., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01449 · Cited by 32 · see citing works
Saifullah, A. B., Komine, O., Dong, Y., Fukumoto, K., Sobue, A., Endo, F., Saito, T., Saido, T. C., Yamanaka, K., & Mizoguchi, H. (2020) · Molecular Brain · doi:10.1186/s13041-020-00690-6 · Cited by 30 · see citing works
Self-citationInnate immunity in Alzheimer’s disease: the relevance of animal models?
Franco-Bocanegra, D., Nicoll, J. A. R., & Boche, D. (2017) · Journal of Neural Transmission · doi:10.1007/s00702-017-1729-4 · Cited by 31 · see citing works
Khoshnan, A., Sabbaugh, A., Calamini, B., Marinero, S., Dunn, D., Yoo, J. H., Ko, J., Lo, D. C., & Patterson, P. H. (2017) · Human Molecular Genetics · doi:10.1093/hmg/ddx315 · Cited by 30 · see citing works
Beckers, L., Geric, I., Stroobants, S., Beel, S., Van Damme, P., D’Hooge, R., & Baes, M. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1442-3 · Cited by 30 · see citing works
Excitatory-neuron-derived interleukin-34 supports cortical developmental microglia function
Devlin, B. A., Nguyen, D. M., Ribeiro, D., Grullon, G., Clark, M. J., Finn, A., Ceasrine, A. M., Oxendine, S. R., Deja, M., Shah, A., et al. (2025) · Immunity · doi:10.1016/j.immuni.2025.06.002 · Cited by 30 · see citing works
Liu, J., Tang, M., Harkin, K., Du, X., Luo, C., Chen, M., & Xu, H. (2020) · Journal of Neuroscience Research · doi:10.1002/jnr.24618 · Cited by 29 · see citing works
Martin, S. P., & Leeman-Markowski, B. A. (2024) · Frontiers in Neurology · doi:10.3389/fneur.2023.1287545 · Cited by 28 · see citing works
Microglial dysfunction in Alzheimer's disease: Mechanisms, emerging therapies, and future directions
Azmal, M., Paul, J. K., Prima, F. S., Haque, A. N. M. S. N. B., Meem, M., & Ghosh, A. (2025) · Experimental Neurology · doi:10.1016/j.expneurol.2025.115374 · Cited by 28 · see citing works
Heme Oxygenase-1 Dysregulation in the Brain: Implications for HIVAssociated Neurocognitive Disorders
Ambegaokar, S. S., & Kolson, D. L. (2014) · Current HIV Research · doi:10.2174/1570162x12666140526122709 · Cited by 28 · see citing works
de Rojas, I., Moreno-Grau, S., Tesi, N., Grenier-Boley, B., Andrade, V., Jansen, I., Pedersen, N. L., Stringa, N., Zettergren, A., Hernández, I., et al. (2019) · doi:10.1101/19012021 · Cited by 28 · see citing works
Fang, M., Yamasaki, R., Li, G., Masaki, K., Yamaguchi, H., Fujita, A., Isobe, N., & Kira, J. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02588 · Cited by 27 · see citing works
Sánchez-Niño, M. D., Sanz, A. B., & Ortíz, A. (2016) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfw026 · Cited by 26 · see citing works
1α,25-Dihydroxyvitamin D3 up-regulates IL-34 expression in SH-SY5Y neural cells
Zhang, D., Li, M., Dong, Y., Zhang, X., Liu, X., Chen, Z., Zhu, Y., Wang, H., Liu, X., Zhu, J., et al. (2017) · Innate Immunity · doi:10.1177/1753425917725391 · Cited by 26 · see citing works
Martin-Estebane, M., & Gomez-Nicola, D. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.00149 · Cited by 25 · see citing works
Freuchet, A., Salama, A., Bézie, S., Tesson, L., Remy, S., Humeau, R., Règue, H., Sérazin, C., Flippe, L., Peterson, P., et al. (2022) · Clinical and Translational Medicine · doi:10.1002/ctm2.988 · Cited by 22 · see citing works
Genome-wide association studies of brain structure and function in the UK BiobankPreprint
Elliott, L. T., Sharp, K., Alfaro‐Almagro, F., Shi, S., Miller, K. L., Douaud, G., Marchini, J., & Smith, S. M. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/178806 · Cited by 22 · see citing works
Role of IL-34 and its receptors in inflammatory diseases
Shang, J., Xu, Y., Pu, S., Sun, X., & Gao, X. (2023) · Cytokine · doi:10.1016/j.cyto.2023.156348 · Cited by 21 · see citing works
Truong, A. D., Hong, Y., Lee, J., Lee, K., Kil, D. Y., Lillehoj, H. S., & Hong, Y. H. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19061665 · Cited by 21 · see citing works
Neuron–microglia interactions in neuroinflammation
Mizuno, T. (2015) · Clinical and Experimental Neuroimmunology · doi:10.1111/cen3.12228 · Cited by 20 · see citing works
Self-citationDevelopment of a culture system to induce microglia‐like cells from haematopoietic cells
Noto, D., Sakuma, H., Takahashi, K., Saika, R., Saga, R., Yamada, M., Yamamura, T., & Miyake, S. (2013) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12086 · Cited by 21 · see citing works
Alzheimer’s Disease Genetics: A Dampened Microglial Response?
Chatila, Z. K., & Bradshaw, E. M. (2021) · The Neuroscientist · doi:10.1177/10738584211024531 · Cited by 20 · see citing works
Naj, A. C., Leonenko, G., Jian, X., Grenier‐Boley, B., Dalmasso, M. C., Bellenguez, C., Jin, S., Zhao, Y., van der Lee, S. J., Sims, R., et al. (2021) · medRxiv · doi:10.1101/2021.03.14.21253553 · Cited by 17 · see citing works
Self-citation
- Authors
- Mizuno, T., Doi, Y., Mizoguchi, H., Jin, S., Noda, M., Sonobe, Y., Takeuchi, H., & Suzumura, A.
- Affiliations
- Research Institute of Environmental Medicine, Nagoya University (JP)
- Corresponding author
- Mizuno, Tetsuya
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2011-10
- Volume
- 179
- Issue
- 4
- Pages
- 2016-2027
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC3181379
- OpenAlex
- W2093493917
- Cited by
- 159
- References
- 38
- Citations by year
- 2026: 10 · 2025: 10 · 2024: 10 · 2023: 13 · 2022: 10 · 2021: 14 · 2020: 13 · 2019: 13 · 2018: 7 · 2017: 11 · 2016: 9 · 2015: 7 · 2014: 7 · 2013: 12 · 2012: 12
- FWCI
- 5.65
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal Of Pathology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- National Institute of Biomedical Innovation
- 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
- IL-34, microglia, amyloid-beta oligomers, Alzheimer's disease, neuroprotection, amyloid-beta clearance, insulin-degrading enzyme, heme oxygenase-1, oxidative stress, colony-stimulating factor 1 receptor, associative learning, APP/PS1 mice, neuroinflammation
- MeSH terms
- Alzheimer Disease, Animals, Antioxidants, Disease Models, Animal, Humans, Injections, Intraventricular, Insulysin, Interleukins, Learning, Mice, Inbred C57BL, Mice, Transgenic, Neurons, Up-Regulation, Amyloid beta-Peptides, Microglia, Neuroprotective Agents, Coculture Techniques, Protein Structure, Quaternary, Cell Proliferation, Mice, Heme Oxygenase-1
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