Microglia in ALS: The Good, The Bad, and The Resting
Abstract
Inflammation, including microglial activation and T cell infiltration, is a neuropathological hallmark of amyotrophic lateral sclerosis (ALS), a rapidly progressing neurodegenerative disease. The identification of mutations in the gene for Cu2+/Zn2+ superoxide dismutase (SOD1) from patients with an inherited form of ALS enabled the creation of transgenic mice overexpressing mutant forms of SOD1 (mSOD1) which develop a motoneuron disease that resembles the disease seen in ALS patients. These transgenic mice display similar inflammatory reactions at sites of motoneuron injury as detected in ALS patients, enabling the observation that this inflammation is not simply a late consequence of motoneuron degeneration, but actively contributes to the balance between neuroprotection and neurotoxicity. The microglial and T cell activation states influence the rate of disease progression. Initially, microglia and T cells can slow disease progression, while they may later contribute to the acceleration of disease. Accumulation of intracellular and extracellular misfolded mSOD1 may be key events regulating the transformation from neuroprotective alternatively activated M2 microglia to cytotoxic classically activated M1 microglia. Intracellular and extracellular mSOD1 utilizing different pathways may enhance the production and release of reactive oxygen species (ROS) and augment the inflammatory cytokine cascade from microglia. These ROS and cytokines may increase the susceptibility of motoneurons to glutamate toxicity and inhibit the function and expression of astrocytic glutamate transporters resulting in further neurotoxicity. Thus, the cumulative evidence suggests that inflammation plays a central role in ALS and manipulating these microglial effector functions may potentially modify the outcome of this devastating disease.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In pre-symptomatic mutant SOD1 transgenic mice, activated microglia initially display neuroprotective properties that slow disease progression.
“In pre-symptomatic mutant SOD1 transgenic mice, activated microglia initially display neuroprotective properties that slow disease progression;”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [435]
In mutant SOD1 transgenic mice, continued unabridged neuroinflammation enhances neurodegeneration and accelerates disease progression.
“however, with time the continued and unabridged neuroinflammation only enhances neurodegeneration and accelerates disease progression [434–436].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [435]
Cites
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
Monocyte and macrophage heterogeneity
Gordon, S., & Taylor, P. R. (2005) · Nature Reviews Immunology · doi:10.1038/nri1733 · Cited by 5,190 · see citing works
Microglia: a sensor for pathological events in the CNS
Kreutzberg, G. W. (1996) · Trends in Neurosciences · doi:10.1016/0166-2236(96)10049-7 · Cited by 4,396 · see citing works
Motor Neuron Degeneration in Mice that Express a Human Cu,Zn Superoxide Dismutase Mutation
Gurney, M. E., Pu, H., Chiu, A. Y., Dal Canto, M. C., Polchow, C. Y., Alexander, D. D., Caliendo, J., Hentati, A., Kwon, Y. W., Deng, H.-X., et al. (1994) · Science · doi:10.1126/science.8209258 · Cited by 4,143 · see citing works
Microglia: Active sensor and versatile effector cells in the normal and pathologic brain
Hanisch, U.-K., & Kettenmann, H. (2007) · Nature Neuroscience · doi:10.1038/nn1997 · Cited by 3,676 · see citing works
Macrophage activation and polarization
Martinez, F. O. (2008) · Frontiers in Bioscience · doi:10.2741/2692 · Cited by 3,160 · 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
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
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
Wong, P. C., Pardo, C. A., Borchelt, D., Lee, M. K., Copeland, N. G., Jenkins, N. A., Sisodia, S. S., Cleveland, D. W., & Price, D. L. (1995) · Neuron · doi:10.1016/0896-6273(95)90259-7 · Cited by 1,439 · see citing works
ALS: A Disease of Motor Neurons and Their Nonneuronal Neighbors
Boillée, S., Velde, C. V., & Cleveland, D. W. (2006) · Neuron · doi:10.1016/j.neuron.2006.09.018 · Cited by 1,426 · see citing works
Bruijn, L. I., Becher, M. W., Lee, M. K., Anderson, K. L., Jenkins, N. A., Copeland, N. G., Sisodia, S. S., Rothstein, J. D., Borchelt, D. R., Price, D. L., et al. (1997) · Neuron · doi:10.1016/s0896-6273(00)80272-x · Cited by 1,341 · see citing works
Amyotrophic lateral sclerosis is a distal axonopathy: evidence in mice and man
Fischer, L. R., Culver, D. G., Tennant, P., Davis, A. A., Wang, M.-S., Castellano-Sanchez, A. A., Khan, J., Polak, M. A., & Glass, J. D. (2004) · Experimental Neurology · doi:10.1016/j.expneurol.2003.10.004 · Cited by 1,338 · see citing works
Macrophage Polarization in Bacterial Infections
Benoit, M. E., Desnues, B., & Mège, J. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.6.3733 · Cited by 1,317 · 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
Targeted disruption of the PU.1 gene results in multiple hematopoietic abnormalities
McKercher, S. R., Torbett, B. E., Anderson, K. L., Henkel, G. W., Vestal, D. J., Baribault, H., Klemsz, M., Feeney, A. J., Wu, G. E., Paige, C. J., et al. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00949.x · Cited by 1,130 · 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
Biochemical and functional characterization of three activated macrophage populations
Edwards, J. P., Zhang, X., Frauwirth, K. A., & Mosser, D. M. (2006) · Journal of Leukocyte Biology · doi:10.1189/jlb.0406249 · Cited by 863 · see citing works
CD4 + CD25 + Foxp3 + regulatory T cells induce alternative activation of human monocytes/macrophages
Tiemessen, M. M., Jagger, A. L., Evans, H. G., van Herwijnen, M. J. C., John, S., & Taams, L. S. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0706832104 · Cited by 854 · see citing works
Howland, D., Liu, J., She, Y., Goad, B., Maragakis, N. J., Kim, B. B., Erickson, J., Kulik, J., DeVito, L., Psaltis, G. C., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.032539299 · Cited by 841 · see citing works
CNS immune privilege: hiding in plain sight
Carson, M. J., Doose, J. M., Melchior, B., Schmid, C. D., & Ploix, C. C. (2006) · Immunological Reviews · doi:10.1111/j.1600-065x.2006.00441.x · Cited by 797 · see citing works
Possible involvement of the M2 anti‐inflammatory macrophage phenotype in growth of human gliomas
Komohara, Y., Ohnishi, K., Kuratsu, J., & Takeya, M. (2008) · The Journal of Pathology · doi:10.1002/path.2370 · Cited by 738 · see citing works
Turner, 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
Self-citationRipps, M. E., Huntley, G. W., Hof, P. R., Morrison, J., & Gordon, J. W. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.3.689 · Cited by 725 · see citing works
Buechler, C., Ritter, M., Orsó, E., Langmann, T., Klucken, J., & Schmitz, G. (2000) · Journal of Leukocyte Biology · doi:10.1002/jlb.67.1.97 · Cited by 704 · see citing works
Borchelt, D., Lee, M. K., Slunt, H. S., Guarnieri, M., Xu, Z. S., Wong, P. C., Brown, R. H., Price, D. L., Sisodia, S. S., & Cleveland, D. W. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.17.8292 · Cited by 622 · see citing works
Henkel-Tigges, J., Engelhardt, J., Siklós, L., Simpson, E. P., Kim, S. H., Pan, T., Goodman, J. C., Siddique, T., Beers, D. R., & Appel, S. H. (2003) · Annals of Neurology · doi:10.1002/ana.10805 · Cited by 554 · see citing works
Self-citationImmunologic 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
Pramatarova, A., Laganière, J., Roussel, J., Brisebois, K., & Rouleau, G. A. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-10-03369.2001 · Cited by 482 · see citing works
Beers, D. R., Henkel-Tigges, J., Zhao, W., Wang, J., & Appel, S. H. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0807419105 · Cited by 468 · see citing works
Self-citationThe microglial "activation" continuum: from innate to adaptive responses
Town, T., Nikolic, V., & Tan, J. (2005) · Journal of Neuroinflammation · doi:10.1186/1742-2094-2-24 · Cited by 456 · 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
Self-citationLino, M. M., Schneider, C., & Caroni, P. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-12-04825.2002 · Cited by 424 · see citing works
Expression of the histocompatibility glycoprotein HLA-DR in neurological disease
McGeer, P. L., Itagaki, S., & McGeer, E. G. (1988) · Acta Neuropathologica · doi:10.1007/bf00689592 · Cited by 420 · see citing works
Urushitani, M., Sik, A., Sakurai, T., Nukina, N., Takahashi, R., & Julien, J.-P. (2006) · Nature Neuroscience · doi:10.1038/nn1603 · Cited by 419 · see citing works
Michelucci, A., Heurtaux, T., Grandbarbe, L., Morga, E., & Heuschling, P. (2009) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2009.02.003 · Cited by 411 · see citing works
Geissmann, F., Auffray, C., Palframan, R. T., Wirrig, C., Ciocca, A., Campisi, L., Narni-Mancinelli, É., & Lauvau, G. S. (2008) · Immunology and Cell Biology · doi:10.1038/icb.2008.19 · Cited by 385 · see citing works
Cytokine Effects on Glutamate Uptake by Human Astrocytes
Hu, S., Sheng, W. S., Ehrlich, L. C., Peterson, P. K., & Chao, C. C. (2000) · NeuroImmunoModulation · doi:10.1159/000026433 · Cited by 378 · see citing works
T lymphocytes potentiate endogenous neuroprotective inflammation in a mouse model of ALS
Chiu, I., Chen, A., Zheng, Y., Kosaras, B., Tsiftsoglou, S., Vartanian, T., Brown, R. H., & Carroll, M. (2008) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0804610105 · Cited by 374 · see citing works
Gong, Y. H., Parsadanian, A. S., Andreeva, A., Snider, W. D., & Elliott, J. L. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-02-00660.2000 · Cited by 372 · see citing works
Peroxynitrite Inhibits Glutamate Transporter Subtypes
Trotti, D., Rossi, D., Gjesdal, O., Levy, L. M., Racagni, G., Danbolt, N. C., & Volterra, A. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.11.5976 · Cited by 371 · see citing works
SOD1 mutations disrupt redox-sensitive Rac regulation of NADPH oxidase in a familial ALS model
Harraz, M. M., Marden, J. J., Zhou, W., Zhang, Y., Williams, A. J., Sharov, V. S., Nelson, K., Luo, M., Paulson, H. L., Schöneich, C., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci34060 · Cited by 357 · see citing works
Rakhit, R., Crow, J. P., Lepock, J. R., Kondejewski, L. H., Cashman, N. R., & Chakrabartty, A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m313295200 · Cited by 345 · see citing works
Ponomarev, E. D., Maresz, K., Tan, Y., & Dittel, B. N. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.1922-07.2007 · Cited by 339 · see citing works
Lymphocytic Infiltrates in the Spinal Cord in Amyotrophic Lateral Sclerosis
Engelhardt, J. I., Tajti, J., & Appel, S. H. (1993) · Archives of Neurology · doi:10.1001/archneur.1993.00540010026013 · Cited by 318 · see citing works
Self-citationYamanaka, K., Boillee, S., Roberts, E. A., Garcia, M. L., McAlonis-Downes, M., Mikse, O. R., Cleveland, D. W., & Goldstein, L. S. B. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0802556105 · Cited by 309 · see citing works
Extracellular mutant SOD1 induces microglial‐mediated motoneuron injury
Zhao, W., Beers, D. R., Henkel, J. S., Zhang, W., Urushitani, M., Julien, J., & Appel, S. H. (2010) · Glia · doi:10.1002/glia.20919 · Cited by 288 · see citing works
Self-citationYoshihara, T., Ishigaki, S., Yamamoto, M., Liang, Y., Jun, Niwa, I., Takeuchi, H., Doyu, M., & Sobue, G. (2001) · Journal of Neurochemistry · doi:10.1046/j.0022-3042.2001.00683.x · Cited by 275 · see citing works
Wu, D., Ré, D. B., Nagai, M., Ischiropoulos, H., & Przedborski, S. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0603670103 · Cited by 253 · see citing works
Ezzi, S. A., Urushitani, M., & Julien, J. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04531.x · Cited by 248 · see citing works
Nguyen, M. D., D'Aigle, T., Gowing, G., Julien, J.-P., & Rivest, S. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.4786-03.2004 · Cited by 248 · see citing works
Jaarsma, D., Teuling, E., Haasdijk, E. D., Zeeuw, C. I. D., & Hoogenraad, C. C. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.5258-07.2008 · Cited by 248 · see citing works
Almer, G., Vukosavić, S., Romero, N. B., & Przedborski, S. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.0722415.x · Cited by 231 · see citing works
An immunological epitope selective for pathological monomer-misfolded SOD1 in ALS
Rakhit, R., Robertson, J., Velde, C. V., Horne, P., Ruth, D. M., Griffin, J. K., Cleveland, D. W., Cashman, N. R., & Chakrabartty, A. (2007) · Nature Medicine · doi:10.1038/nm1559 · Cited by 231 · see citing works
Positive and negative regulation of EAAT2 by NF‐κB: a role for N‐myc in TNFα‐controlled repression
Sitcheran, R., Gupta, P., Fisher, P., & Baldwin, A. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600555 · Cited by 226 · see citing works
Hensley, K. (2003) · Neurobiology of Disease · doi:10.1016/s0969-9961(03)00087-1 · Cited by 220 · see citing works
Expanding the Mind: Insulin-Like Growth Factor I and Brain Development
D’Ercole, A. J., & Ye, P. (2008) · Endocrinology · doi:10.1210/en.2008-0920 · Cited by 208 · see citing works
Increased levels of inflammatory chemokines in amyotrophic lateral sclerosis
Kühle, J., Lindberg, R. L. P., Regeniter, A., Mehling, M., Steck, A., Kappos, L., & Czapliński, A. (2009) · European Journal of Neurology · doi:10.1111/j.1468-1331.2009.02560.x · Cited by 202 · see citing works
Hensley, K., Floyd, R. A., Gordon, B., Mou, S., Pye, Q. N., Stewart, C. A., West, M. S., & Williamson, K. S. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.00968.x · Cited by 200 · see citing works
Adaptive Immune Neuroprotection in G93A-SOD1 Amyotrophic Lateral Sclerosis Mice
Banerjee, R., Mosley, R. L., Reynolds, A. D., Dhar, A., Jackson-Lewis, V. R., Gordon, P. H., Przedborski, S., & Gendelman, H. E. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002740 · Cited by 197 · see citing works
Common molecular signature in SOD1 for both sporadic and familial amyotrophic lateral sclerosis
Gruzman, A., Wood, W. L., Alpert, E., Prasad, M. D., Miller, R. G., Rothstein, J. D., Bowser, R. P., Hamilton, R. L., Wood, T. D., Cleveland, D. W., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705044104 · Cited by 190 · see citing works
A CSF biomarker panel for identification of patients with amyotrophic lateral sclerosis
Mitchell, R. M., Freeman, W. M., Randazzo, W. T., Stephens, H., Beard, J. L., Simmons, Z., & Connor, J. R. (2008) · Neurology · doi:10.1212/01.wnl.0000333251.36681.a5 · Cited by 184 · see citing works
Henkel-Tigges, J., Beers, D. R., Siklós, L., & Appel, S. H. (2005) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2005.10.016 · Cited by 181 · see citing works
Self-citationCytokine upregulation in a murine model of familial amyotrophic lateral sclerosis
Elliott, J. L. (2001) · Molecular Brain Research · doi:10.1016/s0169-328x(01)00242-x · Cited by 181 · 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
Self-citationZhao, W., Xie, W., Xiao, Q., Beers, D. R., & Appel, S. H. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04172.x · Cited by 172 · see citing works
Self-citationActivated 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
Self-citationImmunohistochemical characterization of the inflammatory infiltrate in amyotrophic lateral sclerosis
Troost, D., van den Oord, J. J., & de Jong, J. M. B. V. (1990) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.1990.tb01276.x · Cited by 150 · see citing works
Gowing, G., Philips, T., Wijmeersch, B. V., Audet, J., Dewil, M., Bosch, L. V. D., Billiau, A., Robberecht, W., & Julien, J. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.3494-08.2008 · Cited by 150 · see citing works
Increased cytotoxic potential of microglia from ALS‐transgenic mice
Weydt, P., Yuen, E., Ransom, B. R., & Möller, T. (2004) · Glia · doi:10.1002/glia.20062 · Cited by 147 · see citing works
Redox modifier genes in amyotrophic lateral sclerosis in mice
Marden, J. J., Harraz, M. M., Williams, A. J., Nelson, K., Luo, M., Paulson, H., & Engelhardt, J. F. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31265 · Cited by 145 · see citing works
Innate immunity in amyotrophic lateral sclerosis
Moisse, K., & Strong, M. J. (2006) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2006.03.001 · Cited by 141 · see citing works
Ince, P. G., Shaw, P. J., Slade, J. Y., Jones, C., & Hudgson, P. (1996) · Acta Neuropathologica · doi:10.1007/s004010050535 · Cited by 133 · see citing works
Lampson, L. A., Kushner, P. D., & Sobel, R. A. (1990) · Annals of Neurology · doi:10.1002/ana.410280311 · Cited by 128 · see citing works
Liu, Y., Hao, W., Dawson, A., Liu, S., & Fassbender, K. C. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m804446200 · Cited by 117 · 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
Production of monocyte chemoattractant protein‐1 in amyotrophic lateral sclerosis
Baron, P., Bussini, S., Cardin, V., Corbo, M., Conti, G. M., Galimberti, D., Scarpini, E. A., Bresolin, N., Wharton, S. B., Shaw, P. J., et al. (2005) · Muscle & Nerve · doi:10.1002/mus.20376 · Cited by 111 · see citing works
Lymphocytic infiltration in the spinal cord of patients with amyotrophic lateral sclerosis.
Troost, D., van den Oord, J. J., de Jong, J. M. B. V., & Swaab, D. F. (1989) · PubMed · Cited by 101 · see citing works
Wilms, H. (2003) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2003.08.042 · Cited by 100 · see citing works
Activated microglia (BV-2) facilitation of TNF-α-mediated motor neuron death in vitro
He, B. P., Wen, W., & Strong, M. J. (2002) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(02)00141-8 · Cited by 98 · see citing works
Tanaka, M., Kikuchi, H., Ishizu, T., Minohara, M., Osoegawa, M., Motomura, K., Tateishi, T., Ohyagi, Y., & Kira, J. (2006) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/01.jnen.0000232025.84238.e1 · Cited by 97 · see citing works
Kang, J., & Rivest, S. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200705046 · Cited by 94 · see citing works
Inhibition of Astrocyte Glutamate Uptake by Reactive Oxygen Species: Role of Antioxidant Enzymes
Sorg, O., Horn, T. F. W., Yu, N., Gruol, D. L., & Bloom, F. E. (1997) · Molecular Medicine · doi:10.1007/bf03401690 · Cited by 92 · see citing works
Liu, H., Sanelli, T. R., Horne, P., Pioro, E. P., Strong, M. J., Rogaeva, E. A., Bilbao, J. M., Zinman, L. H., & Robertson, J. (2009) · Annals of Neurology · doi:10.1002/ana.21704 · Cited by 88 · see citing works
Fendrick, S. E., Xue, Q., & Streit, W. J. (2007) · Journal of Neuroinflammation · doi:10.1186/1742-2094-4-9 · Cited by 88 · see citing works
Dimayuga, F. O., Wang, C., Clark, J. M., Dimayuga, E. R., Smith, V. D., & Bruce‐Keller, A. J. (2006) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2006.10.003 · Cited by 87 · see citing works
Urushitani, M., Ezzi, S. A., Matsuo, A., Tooyama, I., & Julien, J. (2008) · The FASEB Journal · doi:10.1096/fj.07-092783 · Cited by 86 · see citing works
Piani, D., Frei, K., Pfister, H.-W., & Fontana, A. (1993) · Journal of Neuroimmunology · doi:10.1016/0165-5728(93)90063-5 · Cited by 86 · see citing works
Miralles, V. J., Martı́nez-López, I., Zaragozá, R., Borrás, E., Garcı́a, C., Pallardó, F. V., & Vinã, J. R. (2001) · Brain Research · doi:10.1016/s0006-8993(01)03124-9 · Cited by 85 · see citing works
Kim, S., Choi, S., Chao, W., & Volsky, D. J. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.02128.x · Cited by 64 · see citing works
Nagata, T., Nagano, I., Shiote, M., Narai, H., Murakami, T., Hayashi, T., Shoji, M., & Abe, K. (2007) · Neurological Research · doi:10.1179/016164107x229795 · Cited by 64 · see citing works
Protective and regenerative effects of the GH/IGF-I axis on the brain.
Isgaard, J., Åberg, N. D., & Nilsson, M. D. (2007) · PubMed · Cited by 63 · see citing works
Liao, S., & Chen, C. (2001) · Neuroscience Letters · doi:10.1016/s0304-3940(01)01499-9 · Cited by 51 · see citing works
Chondroitin sulfate disaccharide stimulates microglia to adopt a novel regulatory phenotype
Ebert, S., Schoeberl, T., Walczak, Y., Stoecker, K., Stempfl, T., Moehle, C., Weber, B. H. F., & Langmann, T. (2008) · Journal of Leukocyte Biology · doi:10.1189/jlb.0208138 · Cited by 50 · see citing works
Rentzos, M., Nikolaou, C., Rombos, A., Boufidou, F., Zoga, M., Dimitrakopoulos, A., Tsoutsou, A., & Vassilopoulos, D. (2007) · Amyotrophic Lateral Sclerosis · doi:10.1080/17482960701419232 · Cited by 48 · see citing works
Transforming Growth Factor-β: Neuronal and Glial Expression in CNS Degenerative Diseases
Lippa, C. F., Smith, T. W., & Flanders, K. C. (1995) · Neurodegeneration · doi:10.1006/neur.1995.0051 · Cited by 44 · see citing works
Inflammatory mediators and growth factors in the spinal cord of G93A SOD1 rats
Xie, Y., Weydt, P., Howland, D., Kliot, M., & Möller, T. (2004) · Neuroreport · doi:10.1097/00001756-200411150-00016 · Cited by 38 · see citing works
Modulation of No and cytokines in microglial cells by Cu/Zn-superoxide dismutase
Chang, S.-C., Kao, M., Fu, M.-T., & Lin, C. (2001) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(01)00691-8 · Cited by 30 · see citing works
Gene, Cell, and Axon Changes in the Familial Amyotrophic Lateral Sclerosis Mouse Sensorimotor Cortex
Kassa, R., Mariotti, R., Bonaconsa, M., Bertini, G., & Bentivoglio, M. (2008) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181922572 · Cited by 27 · see citing works
The NADPH oxidase is involved in lipopolysaccharide-mediated motor neuron injury
Li, B., Guo, Y., Sun, M., Dong, H., Wu, S., Wu, D.-X., & Li, C. (2008) · Brain Research · doi:10.1016/j.brainres.2008.06.024 · Cited by 21 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Differential Roles of M1 and M2 Microglia in Neurodegenerative Diseases
Tang, Y., & Le, W. (2016) · Molecular Neurobiology · doi:10.1007/s12035-014-9070-5 · Cited by 2,190 · see citing works
Microglial <scp>M1/M2</scp> polarization and metabolic states
Orihuela, R., McPherson, C. A., & Harry, G. J. (2016) · British Journal of Pharmacology · doi:10.1111/bph.13139 · Cited by 2,070 · 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
Microglia Induce Motor Neuron Death via the Classical NF-κB Pathway in Amyotrophic Lateral Sclerosis
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., et al. (2014) · Neuron · doi:10.1016/j.neuron.2014.01.013 · Cited by 638 · 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
Stansley, B., Post, J., & Hensley, K. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-115 · Cited by 419 · see citing works
Brettschneider, J., Toledo, J. B., Van Deerlin, V. M., Elman, L., McCluskey, L., Lee, V. M.-Y., & Trojanowski, J. Q. (2012) · PLoS ONE · doi:10.1371/journal.pone.0039216 · Cited by 268 · see citing works
Molecular Imaging of Microglial Activation in Amyotrophic Lateral Sclerosis
Corcia, P., Tauber, C., Vercoullie, J., Arlicot, N., Prunier, C., Praline, J., Nicolas, G., Venel, Y., Hommet, C., Baulieu, J.-L., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0052941 · Cited by 249 · see citing works
Autophagy and ALS: mechanistic insights and therapeutic implications
Chua, J. P., De Calbiac, H., Kabashi, E., & Barmada, S. J. (2022) · Autophagy · doi:10.1080/15548627.2021.1926656 · Cited by 189 · 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
PU.1 regulates Alzheimer’s disease-associated genes in primary human microglia
Rustenhoven, J., Smith, A. M., Smyth, L. C., Jansson, D., Scotter, E. L., Swanson, M. E. V., Aalderink, M., Coppieters, N., Narayan, P., Handley, R., et al. (2018) · Molecular Neurodegeneration · doi:10.1186/s13024-018-0277-1 · Cited by 155 · see citing works
Dysfunction of Optineurin in Amyotrophic Lateral Sclerosis and Glaucoma
Toth, R. P., & Atkin, J. D. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01017 · Cited by 114 · 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
Apolloni, S., Amadio, S., Montilli, C., Volonte, C., & D'Ambrosi, N. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt259 · Cited by 109 · see citing works
Risk factors and emerging therapies in amyotrophic lateral sclerosis
Nowicka, N., Juranek, J., Juranek, J. K., & Wojtkiewicz, J. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20112616 · Cited by 106 · see citing works
Ataka, K., Asakawa, A., Nagaishi, K., Kaimoto, K., Sawada, A., Hayakawa, Y., Tatezawa, R., Inui, A., & Fujimiya, M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0081744 · Cited by 89 · see citing works
The Neuroinflammatory Response in ALS: The Roles of Microglia and T Cells
Lewis, C.-A., Manning, J., Rossi, F., & Krieger, C. (2012) · Neurology Research International · doi:10.1155/2012/803701 · Cited by 76 · see citing works
Implications of Microglia in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia
Haukedal, H., & Freude, K. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.02.004 · Cited by 68 · see citing works
- Authors
- Henkel, J. S., Beers, D. R., Zhao, W., & Appel, S. H.
- Affiliations
- Houston Methodist (US)
- Venue
- Journal of Neuroimmune Pharmacology
- Published
- 2009-09-03
- Volume
- 4
- Issue
- 4
- Pages
- 389-398
- ISSN
- 1557-1890 (ISSN-L)
- 1557-1904
- OpenAlex
- W1970433280
- Cited by
- 353
- References
- 101
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 15 · 2023: 13 · 2022: 21 · 2021: 21 · 2020: 16 · 2019: 17 · 2018: 19 · 2017: 23 · 2016: 28 · 2015: 27 · 2014: 29 · 2013: 30 · 2012: 41
- FWCI
- 2.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Neuroimmune Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Muscular Dystrophy Association
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Keywords
- amyotrophic lateral sclerosis, microglia, neuroinflammation, SOD1 mutations, transgenic mice, motor neuron degeneration, M1/M2 microglial polarization, reactive oxygen species, cytokines, glutamate excitotoxicity, T cell infiltration
- MeSH terms
- Amyotrophic Lateral Sclerosis, Animals, Humans, Motor Neurons, Signal Transduction, Resting Phase, Cell Cycle, Microglia, Disease Progression
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
