Microglia Induce Motor Neuron Death via the Classical NF-κB Pathway in Amyotrophic Lateral Sclerosis
Open accessAbstract
Neuroinflammation is one of the most striking hallmarks of amyotrophic lateral sclerosis (ALS). Nuclear factor-kappa B (NF-κB), a master regulator of inflammation, is upregulated in spinal cords of ALS patients and SOD1-G93A mice. In this study, we show that selective NF-κB inhibition in ALS astrocytes is not sufficient to rescue motor neuron (MN) death. However, the localization of NF-κB activity and subsequent deletion of NF-κB signaling in microglia rescued MNs from microglial-mediated death in vitro and extended survival in ALS mice by impairing proinflammatory microglial activation. Conversely, constitutive activation of NF-κB selectively in wild-type microglia induced gliosis and MN death in vitro and in vivo. Taken together, these data provide a mechanism by which microglia induce MN death in ALS and suggest a novel therapeutic target that can be modulated to slow the progression of ALS and possibly other neurodegenerative diseases by which microglial activation plays a role.
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Multiple sclerosis, ALS, and spinal cord injury are associated with chronic activation of resident immune cells, microglia.
“These disorders (e.g. multiple sclerosis, ALS, spinal cord injury) are associated with chronic activation of resident immune cells, microglia2–4.”
From Central nervous system regeneration is driven by microglia necroptosis and repopulation (2019) · cites this paper as [2]
Restraining microglial activation by ablating NF-kappaB signaling rescues motor neurons from microglia-mediated death in vitro and extends survival of SOD1G93A mice.
“restraining microglial activation by ablating NF-κB signaling rescued motor neurons from microglia-mediated death in vitro and extended survival of SOD1G93A mice (151).”
From Microglia Function in the Central Nervous System During Health and Neurodegeneration (2017) · cites this paper as [151]
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Exploring the full spectrum of macrophage activation
Mosser, D. M., & Edwards, J. P. (2008) · Nature Reviews Immunology · doi:10.1038/nri2448 · Cited by 9,144 · see citing works
Rosen, D. R., Siddique, T., Patterson, D., Figlewicz, D. A., Sapp, P., Hentati, A., Donaldson, D., Goto, J., O'Regan, J. P., Deng, H.-X., et al. (1993) · Nature · doi:10.1038/362059a0 · Cited by 7,062 · see citing works
Shared Principles in NF-κB Signaling
Hayden, M. S., & Ghosh, S. (2008) · Cell · doi:10.1016/j.cell.2008.01.020 · Cited by 4,814 · see citing works
Missing Pieces in the NF-κB Puzzle
Ghosh, S., & Karin, M. (2002) · Cell · doi:10.1016/s0092-8674(02)00703-1 · Cited by 3,638 · cited 2× · see citing works
“We evaluated the efficiency of NF-kB induction by measuring nitric oxide (NO) and TNF-a levels in the coculture medium, both of which are products of classical NF-kB activation and inflammatory microglia (Ghosh and Karin, 2002).”
Regulation and Function of NF-κB Transcription Factors in the Immune System
Vallabhapurapu, S., & Karin, M. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132641 · Cited by 2,578 · see citing works
Kigerl, K. A., Gensel, J. C., Ankeny, D. P., Alexander, J. K., Donnelly, D. J., & Popovich, P. G. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.3257-09.2009 · Cited by 2,130 · see citing works
Self-citationMicroglial 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
Directed differentiation of embryonic stem cells into motor neurons.
Wichterle, H., Lieberam, I., Porter, J. A., & Jessell, T. (2002) · Cell · doi:10.1016/s0092-8674(02)00835-8 · Cited by 1,792 · see citing works
Onset and Progression in Inherited ALS Determined by Motor Neurons and Microglia
Boillée, S., Yamanaka, K., Lobsiger, C. S., Copeland, N. G., Jenkins, N. A., Kassiotis, G., Kollias, G., & Cleveland, D. W. (2006) · Science · doi:10.1126/science.1123511 · Cited by 1,623 · see citing works
Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes
Foust, K. D., Nurre, E., Montgomery, C. L., Hernandez, A., Chan, C. M., & Kaspar, B. K. (2009) · Nature Biotechnology · doi:10.1038/nbt.1515 · Cited by 1,456 · cited 3× · see citing works
“However, targeting NF-kB is complicated due to its diverse functions in different cell types in the CNS and periphery.”
Self-citationControl of Synaptic Strength by Glial TNFα
Beattie, E. C., Stellwagen, D., Morishita, W., Bresnahan, J. C., Ha, B. K., Von Zastrow, M., Beattie, M. S., & Malenka, R. C. (2002) · Science · doi:10.1126/science.1067859 · Cited by 1,344 · see citing works
Mutations of optineurin in amyotrophic lateral sclerosis
Maruyama, H., Morino, H., Ito, H., Izumi, Y., Kato, H., Watanabe, Y., Kinoshita, Y., Kamada, M., Nodera, H., Suzuki, H., et al. (2010) · Nature · doi:10.1038/nature08971 · Cited by 1,265 · see citing works
Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons
Nagai, M., Re, D. B., Nagata, T., Chalazonitis, A., Jessell, T. M., Wichterle, H., & Przedborski, S. (2007) · Nature Neuroscience · doi:10.1038/nn1876 · Cited by 1,220 · see citing works
Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis
Yamanaka, K., Chun, S. J., Boillee, S., Fujimori-Tonou, N., Yamashita, H., Gutmann, D. H., Takahashi, R., Misawa, H., & Cleveland, D. W. (2008) · Nature Neuroscience · doi:10.1038/nn2047 · Cited by 1,140 · see citing works
Wild-Type Nonneuronal Cells Extend Survival of SOD1 Mutant Motor Neurons in ALS Mice
Clement, A. M., Nguyen, M. D., Roberts, E. A., Garcia, M. L., Boillée, S., Rule, M., McMahon, A. P., Doucette, W. T., Siwek, D. F., Ferrante, R. J., et al. (2003) · Science · doi:10.1126/science.1086071 · Cited by 1,101 · see citing works
Wang, C.-Y., Cusack, J., Liu, R., & Baldwin, A. (1999) · Nature Medicine · doi:10.1038/7410 · Cited by 1,088 · see citing works
Non–cell autonomous effect of glia on motor neurons in an embryonic stem cell–based ALS model
Di Giorgio, F. P., Carrasco, M. A., Siao, M. C., Maniatis, T., & Eggan, K. (2007) · Nature Neuroscience · doi:10.1038/nn1885 · Cited by 799 · see citing works
Review: microglia of the aged brain: primed to be activated and resistant to regulation
Norden, D. M., & Godbout, J. P. (2013) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2012.01306.x · Cited by 792 · see citing works
Self-citationAstrocytes from familial and sporadic ALS patients are toxic to motor neurons
Haidet-Phillips, A. M., Hester, M. E., Miranda, C. J., Meyer, K., Braun, L., Frakes, A., Song, S., Likhite, S., Murtha, M. J., Foust, K. D., et al. (2011) · Nature Biotechnology · doi:10.1038/nbt.1957 · Cited by 782 · see citing works
Self-citationTurner, M. R., Cagnin, A., Turkheimer, F. E., Miller, C. C. J., Shaw, C. E., Brooks, D. J., Leigh, P. N., & Banati, R. B. (2004) · Neurobiology of Disease · doi:10.1016/j.nbd.2003.12.012 · Cited by 737 · see citing works
Beers, D. R., Henkel, J. S., Xiao, Q., Zhao, W., Wang, J., Yen, A. A., Siklos, L., McKercher, S. R., & Appel, S. H. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0607423103 · Cited by 733 · see citing works
Sasmono, R. T., Oceandy, D., Pollard, J. W., Tong, W., Pavli, P., Wainwright, B. J., Ostrowski, M. C., Himes, S. R., & Hume, D. A. (2003) · Blood · doi:10.1182/blood-2002-02-0569 · Cited by 662 · see citing works
hGFAP‐cre transgenic mice for manipulation of glial and neuronal function in vivo
Zhuo, L., Theis, M., Álvarez-Maya, I., Brenner, M., Willecke, K., & Messing, A. (2001) · genesis · doi:10.1002/gene.10008 · Cited by 660 · see citing works
Chiu, I. M., Morimoto, E. T. A., Goodarzi, H., Liao, J. T., O’Keeffe, S., Phatnani, H. P., Muratet, M., Carroll, M. C., Levy, S., Tavazoie, S., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.06.018 · Cited by 651 · see citing works
Erblich, B., Zhu, L., Etgen, A. M., Dobrenis, K., & Pollard, J. W. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026317 · Cited by 649 · see citing works
Neuroinflammation in amyotrophic lateral sclerosis: role of glial activation in motor neuron disease
Philips, T., & Robberecht, W. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(11)70015-1 · Cited by 646 · see citing works
Roles for NF-κB in nerve cell survival, plasticity, and disease
Mattson, M. P., & Meffert, M. K. (2006) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401837 · Cited by 597 · see citing works
Immunologic reactions in amyotrophic lateral sclerosis brain and spinal cord tissue.
Kawamata, T., Akiyama, H., Yamada, T., & McGeer, P. L. (1992) · PubMed Central · Cited by 546 · see citing works
Macrophage Apoptosis by Anthrax Lethal Factor Through p38 MAP Kinase Inhibition
Park, J. M., Greten, F. R., Li, Z., & Karin, M. (2002) · Science · doi:10.1126/science.1073163 · Cited by 500 · see citing works
Giorgio, F. P. D., Boulting, G. L., Bobrowicz, S., & Eggan, K. C. (2008) · Cell stem cell · doi:10.1016/j.stem.2008.09.017 · Cited by 488 · see citing works
Modulating inflammatory monocytes with a unique microRNA gene signature ameliorates murine ALS
Butovsky, O., Siddiqui, S., Gabriely, G., Lanser, A. J., Dake, B., Murugaiyan, G., Doykan, C. E., Wu, P. M., Gali, R. R., Iyer, L. K., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci62636 · Cited by 481 · see citing works
Marchetto, M. C., Muotri, A. R., Mu, Y., Smith, A. M., Cezar, G. G., & Gage, F. H. (2008) · Cell stem cell · doi:10.1016/j.stem.2008.10.001 · Cited by 455 · see citing works
Immune reactivity in a mouse model of familial ALS correlates with disease progression
Alexianu, M. E., Kozovska, M., & Appel, S. H. (2001) · Neurology · doi:10.1212/wnl.57.7.1282 · Cited by 438 · see citing works
Beers, D. R., Henkel-Tigges, J., Zhao, W., Wang, J., Huang, A., Wen, S., Liao, B., & Appel, S. H. (2011) · Brain · doi:10.1093/brain/awr074 · Cited by 426 · see citing works
Kaltschmidt, B., & Kaltschmidt, C. (2009) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a001271 · Cited by 392 · see citing works
Microglia in ALS: The Good, The Bad, and The Resting
Henkel, J. S., Beers, D. R., Zhao, W., & Appel, S. H. (2009) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-009-9171-5 · Cited by 353 · see citing works
Swarup, V., Phaneuf, D., Dupré, N., Petri, S., Strong, M. J., Križ, J., & Julien, J. (2011) · The Journal of Experimental Medicine · doi:10.1084/jem.20111313 · Cited by 338 · see citing works
Ruocco, M. G., Maeda, S., Park, J. M., Lawrence, T., Hsu, L.-C., Cao, Y., Schett, G., Wagner, E. F., & Karin, M. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20042081 · Cited by 252 · see citing works
Kaltschmidt, B., Ndiaye‐Lobry, D., Körte, M., Pothion, S., Arbibe, L., Prüllage, M., Pfeiffer, J., Lindecke, A., Staiger, V., Israël, A., et al. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.26.8.2936-2946.2006 · Cited by 229 · see citing works
Foust, K. D., Salazar, D. L., Likhite, S. B., Ferraiuolo, L., Ditsworth, D., Ilieva, H. S., Meyer, K., Schmelzer, L., Braun, L., Cleveland, D. W., et al. (2013) · Molecular Therapy · doi:10.1038/mt.2013.211 · Cited by 205 · see citing works
Self-citationNeuroinflammation modulates distinct regional and temporal clinical responses in ALS mice
Beers, D. R., Zhao, W., Liao, B., Kano, O., Wang, J., Huang, A., Appel, S. H., & Henkel-Tigges, J. (2010) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2010.12.008 · Cited by 197 · see citing works
IKKβ Is Required for Peripheral B Cell Survival and Proliferation
Li, Z., Omori, S. A., Labuda, T., Karin, M., & Rickert, R. C. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.9.4630 · Cited by 192 · see citing works
Mantovani, S., Garbelli, S., Pasini, A., Alimonti, D., Perotti, C. G., Melazzini, M. G., Bendotti, C., & Mora, G. (2009) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2009.02.012 · Cited by 190 · see citing works
Mutant SOD1<sup>G93A</sup> microglia are more neurotoxic relative to wild‐type microglia
Xiao, Q., Zhao, W., Beers, D. R., Yen, A. A., Xie, W., Henkel, J. S., & Appel, S. H. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04677.x · Cited by 174 · see citing works
Activated Microglia Initiate Motor Neuron Injury by a Nitric Oxide and Glutamate-Mediated Mechanism
Zhao, W., Xie, W., Le, W., Beers, D. R., He, Y., Henkel-Tigges, J., Simpson, E. P., Yen, A. A., Xiao, Q., & Appel, S. H. (2004) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/63.9.964 · Cited by 169 · see citing works
NF-κB signalling regulates the growth of neural processes in the developing PNS and CNS
Gutiérrez, H., Hale, V. A., Dolcet, X., & Davies, A. M. (2005) · Development · doi:10.1242/dev.01702 · Cited by 167 · see citing works
Uranishi, H., Tetsuka, T., Yamashita, M., Asamitsu, K., Shimizu, M., Itoh, M., & Okamoto, T. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m011176200 · Cited by 158 · see citing works
Miranda, C. J., Braun, L., Jiang, Y., Hester, M. E., Zhang, L., Riolo, M., Wang, H., Rao, M., Altura, R. A., & Kaspar, B. K. (2012) · Aging Cell · doi:10.1111/j.1474-9726.2012.00816.x · Cited by 153 · see citing works
Self-citationNguyen, M. D., Julien, J., & Rivest, S. (2001) · Annals of Neurology · doi:10.1002/ana.1256 · Cited by 129 · see citing works
Kamei, Y., Inagaki, N., Nishizawa, M., Tsutsumi, O., Taketani, Y., & Inagaki, M. (1998) · Glia · doi:10.1002/(sici)1098-1136(199807)23:3 · Cited by 114 · see citing works
Magness, S. T., Jijon, H. B., Fisher, N. V. H., Sharpless, N. E., Brenner, D. A., & Jobin, C. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.3.1561 · Cited by 113 · see citing works
Gowing, G., Dequen, F., Soucy, G., & Julien, J. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.0602-06.2006 · Cited by 105 · see citing works
A new method to isolate microglia from adult mice and culture them for an extended period of time
Moussaud, S., & Draheim, H. J. (2010) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2010.01.017 · Cited by 104 · see citing works
Taoufik, E., Tseveleki, V., Chu, S. Y., Tselios, T. V., Karin, M., Lassmann, H., Szymkowski, D. E., & Probert, L. (2011) · Brain · doi:10.1093/brain/awr203 · Cited by 94 · see citing works
Lerman, B. J., Hoffman, E. P., Sutherland, M. L., Bouri, K., Hsu, D. K., Liu, F., Rothstein, J. D., & Knoblach, S. M. (2012) · Brain and Behavior · doi:10.1002/brb3.75 · Cited by 88 · see citing works
Crosio, C., Valle, C., Casciati, A., Iaccarino, C., & Carrı̀, M. T. (2011) · PLoS ONE · doi:10.1371/journal.pone.0017187 · Cited by 72 · see citing works
Ismail, A., Cooper-Knock, J., Highley, J. R., Milano, A., Kirby, J., Goodall, E., Lowe, J., Scott, I., Constantinescu, C. S., Walters, S. J., et al. (2013) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp-2012-303326 · Cited by 65 · see citing works
Generation and Characterization of MacGreen Mice, the Cfs1r-EGFP Transgenic Mice
Sasmono, R. T., & Williams, E. M. (2011) · Methods in molecular biology · doi:10.1007/978-1-61779-527-5_11 · Cited by 58 · see citing works
Astroglial nuclear factor‐κB regulates learning and memory and synaptic plasticity in female mice
Bracchi-Ricard, V. C., Brambilla, R., Levenson, J. M., Hu, W., Bramwell, A., Sweatt, J. D., Green, E. J., & Bethea, J. R. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04993.x · Cited by 58 · see citing works
Emmanouil, M., Taoufik, E., Tseveleki, V., Vamvakas, S. M., Tselios, T. V., Karin, M., Lassmann, H., & Probert, L. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0900834 · Cited by 39 · see citing works
Sako, W., Ito, H., Yoshida, M., Koizumi, H., Kamada, M., Fujita, K., Hashizume, Y., Izumi, Y., & Kaji, R. (2012) · Clinical Neuropathology · doi:10.5414/np300493 · Cited by 30 · see citing works
Survival in a transgenic model of fals is independent of inos expression
Son, M., Fathallah‐Shaykh, H. M., & Elliott, J. L. (2001) · Annals of Neurology · doi:10.1002/ana.1104 · Cited by 30 · see citing works
Is prostaglandin E2 a pathogenic factor in amyotrophic lateral sclerosis?
Almer, G., Kikuchi, H., Teismann, P., & Przedborski, S. (2006) · Annals of Neurology · doi:10.1002/ana.20847 · Cited by 16 · see citing works
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- Crosio C Valle C Casciati A Iaccarino C Carrì MT 2011b Astroglial Inhibition of NF-κB Does Not Ameliorate Disease Onset and Progression in a Mouse Model for Amyotrophic Lateral Sclerosis (ALS) PLoS ONE 6 e17187 21445241 PMC3060799
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Colonna, M., & Butovsky, O. (2017) · Annual Review of Immunology · doi:10.1146/annurev-immunol-051116-052358 · Cited by 2,894 · see citing works
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Escartin, C., Galea, E., Lakatos, A., O’Callaghan, J. P., Petzold, G. C., Serrano-Pozo, A., Steinhäuser, C., Volterra, A., Carmignoto, G., Agarwal, A., et al. (2021) · Nature Neuroscience · doi:10.1038/s41593-020-00783-4 · Cited by 2,533 · see citing works
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Dissecting molecular cross-talk between Nrf2 and NF-κB response pathways
Wardyn, J. D., Ponsford, A. H., & Sanderson, C. M. (2015) · Biochemical Society Transactions · doi:10.1042/bst20150014 · Cited by 1,200 · see citing works
Microglia in Neuroinflammation and Neurodegeneration: From Understanding to Therapy
Muzio, L., Viotti, A., & Martino, G. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.742065 · Cited by 581 · see citing works
Szalay, G., Martinecz, B., Lénárt, N., Környei, Z., Orsolits, B., Judák, L., Császár, E., Fekete, R., West, B. L., Katona, G., et al. (2016) · Nature Communications · doi:10.1038/ncomms11499 · Cited by 573 · see citing works
Mead, R. J., Shan, N., Reiser, H. J., Marshall, F., & Shaw, P. J. (2023) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00612-2 · Cited by 505 · see citing works
Lee, J.-H., McBrayer, M. K., Wolfe, D. M., Haslett, L. J., Kumar, A., Sato, Y., Lie, P. P. Y., Mohan, P., Coffey, E. E., Kompella, U., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.07.050 · Cited by 358 · see citing works
Dealing with danger in the CNS: the response of the immune system to injury
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Butovsky, O., Jedrychowski, M. P., Cialic, R., Krasemann, S., Murugaiyan, G., Fanek, Z., Greco, D. J., Wu, P. M., Doykan, C. E., Kiner, O., et al. (2015) · Annals of Neurology · doi:10.1002/ana.24304 · Cited by 358 · see citing works
Sankowski, R., Mader, S., & Valdés-Ferrer, S. I. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00028 · Cited by 351 · see citing works
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Ben Haim, L., Ceyzériat, K., Carrillo-de Sauvage, M. A., Aubry, F., Auregan, G., Guillermier, M., Ruiz, M., Petit, F., Houitte, D., Faivre, E., et al. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.3516-14.2015 · Cited by 335 · see citing works
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Spiller, K. J., Restrepo, C. R., Khan, T., Dominique, M. A., Fang, T. C., Canter, R. G., Roberts, C. J., Miller, K. R., Ransohoff, R. M., Trojanowski, J. Q., et al. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0083-7 · Cited by 301 · see citing works
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Bordt, E. A., & Polster, B. M. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.07.033 · Cited by 202 · see citing works
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Gaj, T., Ojala, D. S., Ekman, F. K., Byrne, L. C., Limsirichai, P., & Schaffer, D. V. (2017) · Science Advances · doi:10.1126/sciadv.aar3952 · Cited by 185 · see citing works
Microglia and C9orf72 in neuroinflammation and ALS and frontotemporal dementia
Lall, D., & Baloh, R. H. (2017) · Journal of Clinical Investigation · doi:10.1172/jci90607 · Cited by 175 · see citing works
Genetics of the human microglia regulome refines Alzheimer’s disease risk loci
Kosoy, R., Fullard, J. F., Zeng, B., Bendl, J., Dong, P., Rahman, S., Kleopoulos, S. P., Shao, Z., Girdhar, K., Humphrey, J., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01149-1 · Cited by 168 · see citing works
Glia Crosstalk in Neuroinflammatory Diseases
Bernaus, A., Blanco, S., & Sevilla, A. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.00209 · Cited by 157 · see citing works
Li, Y., Peng, Y., Shen, Y., Zhang, Y., Liu, L., & Yang, X. (2023) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2022.2076064 · Cited by 156 · see citing works
Exploring Sphingolipid Implications in Neurodegeneration
Alessenko, A. V., & Albi, E. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.00437 · Cited by 141 · see citing works
Dysfunction of ABC transporters at the blood-brain barrier: Role in neurological disorders
Gil-Martins, E., Barbosa, D. J., Silva, V., Remião, F., & Silva, R. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107554 · Cited by 152 · see citing works
Béland, L.-C., Markovinovic, A., Jakovac, H., De Marchi, F., Bilic, E., Mazzini, L., Kriz, J., & Munitic, I. (2020) · Brain Communications · doi:10.1093/braincomms/fcaa124 · Cited by 125 · see citing works
Gravel, M., Béland, L.-C., Soucy, G., Abdelhamid, E., Rahimian, R., Gravel, C., & Kriz, J. (2016) · The Journal of Neuroscience · doi:10.1523/jneurosci.0854-15.2016 · Cited by 117 · see citing works
Trias, E., Beilby, P. R., Kovacs, M., Ibarburu, S., Varela, V., Barreto-Núñez, R., Bradford, S. C., Beckman, J. S., & Barbeito, L. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00042 · Cited by 85 · see citing works
Gomes, C., Cunha, C., Nascimento, F., Ribeiro, J. A., Vaz, A. R., & Brites, D. (2019) · Molecular Neurobiology · doi:10.1007/s12035-018-1220-8 · Cited by 79 · see citing works
Rossi, C., Cusimano, M., Zambito, M., Finardi, A., Capotondo, A., Garcia-Manteiga, J. M., Comi, G., Furlan, R., Martino, G., & Muzio, L. (2018) · Cell Death & Disease · doi:10.1038/s41419-018-0288-4 · Cited by 77 · see citing works
Neuroinflammation in Alzheimer’s disease: Pleiotropic roles for cytokines and neuronal pentraxins
Swanson, A., Wolf, T., Sitzmann, A., & Willette, A. A. (2018) · Behavioural Brain Research · doi:10.1016/j.bbr.2018.02.015 · Cited by 72 · see citing works
Regulation of the neurodegenerative process associated to Parkinson's disease by CD4+ T-cells
González, H., Contreras, F., & Pacheco, R. (2015) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-015-9618-9 · Cited by 70 · see citing works
Ubiquilin-2 drives NF-κB activity and cytosolic TDP-43 aggregation in neuronal cells
Picher-Martel, V., Dutta, K., Phaneuf, D., Sobue, G., & Julien, J.-P. (2015) · Molecular Brain · doi:10.1186/s13041-015-0162-6 · Cited by 65 · see citing works
Dutta, K., Patel, P., & Julien, J.-P. (2018) · Experimental Neurology · doi:10.1016/j.expneurol.2018.08.008 · Cited by 56 · see citing works
Mitigation of ALS Pathology by Neuron-Specific Inhibition of Nuclear Factor Kappa B Signaling
Dutta, K., Thammisetty, S. S., Boutej, H., Bareil, C., & Julien, J.-P. (2020) · The Journal of Neuroscience · doi:10.1523/jneurosci.0536-20.2020 · Cited by 55 · see citing works
Eitan, C., Siany, A., Barkan, E., Olender, T., van Eijk, K. R., Moisse, M., Farhan, S. M. K., Danino, Y. M., Yanowski, E., Marmor-Kollet, H., et al. (2022) · Nature Neuroscience · doi:10.1038/s41593-022-01040-6 · Cited by 38 · see citing works
Huang, Z., Liu, Q., Peng, Y., Dai, J., Xie, Y., Chen, W., Long, S., Pei, Z., Su, H., & Yao, X. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.00218 · Cited by 38 · see citing works
Zhou, L., Xu, Z., Oh, Y., Gamuyao, R., Lee, G., Xie, Y., Cho, H., Lee, S., & Duh, E. J. (2021) · JCI Insight · doi:10.1172/jci.insight.93382 · Cited by 34 · see citing works
- Authors
- Frakes, A. E., Ferraiuolo, L., Haidet-Phillips, A. M., Schmelzer, L., Braun, L., Miranda, C. J., Ladner, K. J., Bevan, A. K., Foust, K. D., Godbout, J. P., Popovich, P. G., Guttridge, D. C., & Kaspar, B. K.
- Affiliations
- Nationwide Children's Hospital (US)
- The Ohio State University (US)
- Corresponding author
- Kaspar, Brian K.
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2014-03
- Volume
- 81
- Issue
- 5
- Pages
- 1009-1023
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC3978641
- OpenAlex
- W2101321540
- Cited by
- 638
- References
- 63
- Citations by year
- 2026: 33 · 2025: 43 · 2024: 54 · 2023: 54 · 2022: 61 · 2021: 61 · 2020: 76 · 2019: 57 · 2018: 51 · 2017: 45 · 2016: 47 · 2015: 40 · 2014: 16
- FWCI
- 32.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS644912, R01NS064492, T32NS077984)
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- amyotrophic lateral sclerosis, microglia, motor neuron degeneration, NF-κB signaling, neuroinflammation, microglial activation, gliosis, SOD1 G93A mice, astrocytes, neurodegeneration, therapeutic target
- MeSH terms
- Superoxide Dismutase-1, Age Factors, Amyotrophic Lateral Sclerosis, Animals, Animals, Newborn, Astrocytes, Cell Communication, Disease Models, Animal, Female, Mice, Inbred Strains, Mice, Transgenic, Motor Neurons, Superoxide Dismutase, Signal Transduction, NF-kappa B, Cell Death, Microglia, Coculture Techniques, Mice, Primary Cell Culture
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