Extracellular mutant SOD1 induces microglial‐mediated motoneuron injury
Open accessAbstract
Through undefined mechanisms, dominant mutations in (Cu/Zn) superoxide dismutase‐1 (mSOD1) cause the non‐cell‐autonomous death of motoneurons in inherited amyotrophic lateral sclerosis (ALS). Microgliosis at sites of motoneuron injury is a neuropathological hallmark of ALS. Extracellular mutant SOD1 (mSOD1) causes motoneuron injury and triggers microgliosis in spinal cord cultures, but it is unclear whether the injury results from extracellular mSOD1 directly interacting with motoneurons or is mediated through mSOD1‐activated microglia. To dissociate these potential mSOD1‐mediated neurotoxic mechanisms, the effects of extracellular human mSOD1 G93A or mSOD1 G85R were assayed using primary cultures of motoneurons and microglia. The data demonstrate that exogenous mSOD1 G93A did not cause detectable direct killing of motoneurons. In contrast, mSOD1 G93A or mSOD1 G85R did induce the morphological and functional activation of microglia, increasing their release of pro‐inflammatory cytokines and free radicals. Furthermore, only when microglia was co‐cultured with motoneurons did extracellular mSOD1 G93A injure motoneurons. The microglial activation mediated by mSOD1 G93A was attenuated using toll‐like receptors (TLR) 2, TLR4 and CD14 blocking antibodies, or when microglia lacked CD14 expression. These data suggest that extracellular mSOD1 G93A is not directly toxic to motoneurons but requires microglial activation for toxicity, utilizing CD14 and TLR pathways. This link between mSOD1 and innate immunity may offer novel therapeutic targets in ALS. © 2009 Wiley‐Liss, Inc.
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SR-B2 promotes α-synuclein-microglial interactions and detects misfolded mutant or oxidized SOD1 in diseased motor neurons or extracellular space, making these cells proinflammatory.
“SR-B2 promotes α-synuclein–microglial interactions64 and senses misfolded mutant or oxidized SOD1 in diseased motor neurons or in the extracellular space, rendering these cells proinflammatory85.”
From Microglia in neurodegeneration (2018) · cites this paper as [85]
In primary mouse microglia, SOD1G93A protein caused NLRP3 inflammasome activation and a significant increase in the release of pro-inflammatory factors such as TNF, IL-1β, superoxide, and iNOS.
“For example, in primary mouse microglia, SOD1G93A protein caused NLRP3 inflammasome activation and a significant increase in the release of pro-inflammatory factors such as TNF, IL-1β, superoxide, and iNOS.507”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [507]
Pathological proteins of ALS can be secreted into the extracellular matrix, and these pathological proteins are sensed by microglia, causing microglial activation and pro-inflammatory effect that are harmful to co-cultured motor neurons.
“Additionally, pathological proteins of ALS can be secreted into the extracellular matrix, and these pathological proteins are sensed by microglia, causing microglial activation and pro-inflammatory effect that are harmful to co-cultured motor neurons.”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [507]
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Cites
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
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
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
From charcot to lou gehrig: deciphering selective motor neuron death in als
Cleveland, D. W., & Rothstein, J. D. (2001) · Nature reviews. Neuroscience · doi:10.1038/35097565 · Cited by 1,389 · see citing works
Reaume, A. G., Elliott, J. L., Hoffman, E. K., Kowall, N. W., Ferrante, R. J., Siwek, D. F., Wilcox, H. M., Flood, D. G., Beal, M. F., Brown, R. H., et al. (1996) · Nature Genetics · doi:10.1038/ng0596-43 · Cited by 1,285 · 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
Microglia initiate central nervous system innate and adaptive immune responses through multiple TLRs
Olson, J. K., & Miller, S. D. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.6.3916 · Cited by 1,215 · 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
TLR signaling tailors innate immune responses in human microglia and astrocytes
Jack, C. S., Arbour, N., Manusow, J., Montgrain, V., Blain, M., McCrea, E., Shapiro, A., & Antel, J. P. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.7.4320 · Cited by 734 · cited 1× · see citing works
“Other lines of evidence indeed suggest that CD14/TLRs may contribute to the inflammatory responses initiated by microglia (Jack et al., 2005; Olson and Miller, 2004).”
BackgroundBeers, 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-citationScavenger receptor-mediated adhesion of microglia to β-amyloid fibrils
Khoury, J. E., Hickman, S. E., Thomas, C. A., Cao, L., Silverstein, S. C., & Loike, J. D. (1996) · Nature · doi:10.1038/382716a0 · Cited by 727 · see citing works
Pivotal role for neuronal Toll-like receptors in ischemic brain injury and functional deficits
Tang, S.-C., Arumugam, T. V., Xu, X., Cheng, A., Mughal, M. R., Jo, D. G., Lathia, J. D., Siler, D. A., Chigurupati, S., Ouyang, X., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0702553104 · Cited by 672 · 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-citationCD36 Mediates the Innate Host Response to β-Amyloid
El Khoury, J. B., Moore, K. J., Means, T. K., Leung, J., Terada, K., Toft, M., Freeman, M. W., & Luster, A. D. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20021546 · Cited by 483 · 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
Inflammatory processes in amyotrophic lateral sclerosis
McGeer, P. L., & McGeer, E. G. (2002) · Muscle & Nerve · doi:10.1002/mus.10191 · Cited by 470 · 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-citationMotor Neurons Are Selectively Vulnerable to AMPA/Kainate Receptor-Mediated InjuryIn Vitro
Carriedo, S. G., Yin, H. Z., & Weiss, J. H. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-13-04069.1996 · Cited by 440 · see citing works
Glial cells as intrinsic components of non-cell-autonomous neurodegenerative disease
Lobsiger, C. S., & Cleveland, D. W. (2007) · Nature Neuroscience · doi:10.1038/nn1988 · Cited by 438 · see citing works
Lino, 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
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
Self-citationSOD1 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
Tan, A. S., & Berridge, M. V. (2000) · Journal of Immunological Methods · doi:10.1016/s0022-1759(00)00156-3 · Cited by 330 · see citing works
Yamanaka, 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
The LPS receptor (CD14) links innate immunity with Alzheimer's disease
Fassbender, K., Walter, S., Kühl, S., Landmann, R., Ishii, K., Bertsch, T., Stalder, A. K., Muehlhauser, F., Liu, Y., Ulmer, A. J., et al. (2004) · The FASEB Journal · doi:10.1096/fj.03-0364fje · Cited by 307 · see citing works
Takeuchi, 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 2× · see citing works
“cal neural injury is signaled through an NMDA receptor (Takeuchi et al., 2005), the NMDA receptor antagonist APV did not protect motoneurons from microglia-mediated injury (Zhao et al.”
BackgroundResultFurukawa, Y., & O’Halloran, T. V. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m500482200 · Cited by 275 · 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
Self-citationNguyen, 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
Self-citationJaarsma, 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
Wang, J., Xu, G. M., Gonzales, V., Coonfield, M. L., Fromholt, D., Copeland, N. G., Jenkins, N. A., & Borchelt, D. (2002) · Neurobiology of Disease · doi:10.1006/nbdi.2002.0498 · Cited by 235 · see citing works
Screening of innate immune receptors in neurodegenerative diseases: A similar pattern
Letiembre, M., Liu, Y., Walter, S., Hao, W., Pfander, T., Wrede, A., Schulz-Schaeffer, W., & Fassbender, K. (2009) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.08.018 · Cited by 228 · see citing works
Furukawa, Y., Fu, R., Deng, H., Siddique, T., & O’Halloran, T. V. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0602048103 · Cited by 225 · see citing works
Structure, function and regulation of the Toll/IL‐1 receptor adaptor proteins
Watters, T. M., Kenny, E. F., & O'Neill, L. A. J. (2007) · Immunology and Cell Biology · doi:10.1038/sj.icb.7100095 · Cited by 216 · see citing works
The role of complement and activated microglia in the pathogenesis of Alzheimer's disease
Eikelenboom, P., & Veerhuis, R. (1996) · Neurobiology of Aging · doi:10.1016/0197-4580(96)00108-x · Cited by 206 · 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
CHIP promotes proteasomal degradation of familial ALS‐linked mutant SOD1 by ubiquitinating Hsp/Hsc70
Urushitani, M., Kurisu, J., Tateno, M., Hatakeyama, S., Nakayama, K. I., Kato, S., & Takahashi, R. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02486.x · Cited by 186 · see citing works
Self-citationHenkel-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-citationMutant 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-citationRedox 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
Gorvel, V. A., Garcès, A., de Bovis, B., Filippi, P., Henderson, C. E., Pettmann, B., & deLapeyrière, O. (1999) · Journal of Neuroscience Research · doi:10.1002/(sici)1097-4547(19990101)55:1 · Cited by 144 · see citing works
Oxidized/misfolded superoxide dismutase‐1: the cause of all amyotrophic lateral sclerosis?
Kabashi, E., Valdmanis, P. N., Dion, P. A., & Rouleau, G. A. (2007) · Annals of Neurology · doi:10.1002/ana.21319 · Cited by 140 · see citing works
Townsend, K. P., Town, T., Mori, T., Lue, L., Shytle, D., Sanberg, P. R., Morgan, D., Fernandez, F., Flavell, R. A., & Tan, J. (2005) · European Journal of Immunology · doi:10.1002/eji.200425585 · Cited by 121 · see citing works
Kang, J., & Rivest, S. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200705046 · Cited by 94 · see citing works
Leung, T. F., Tang, N. L. S., Wong, G., & Fok, T. F. (2005) · Current Drug Targets - Inflammation & Allergy · doi:10.2174/1568010053586336 · Cited by 44 · see citing works
Microglia kill amyloid-β1-42 damaged neurons by a CD14-dependent process
Bate, C., Veerhuis, R., Eikelenboom, P., & Williams, A. (2004) · Neuroreport · doi:10.1097/01.wnr.0000132203.76836.16 · Cited by 40 · see citing works
Amyotrophic Lateral Sclerosis from Bench to Bedside
Lomen‐Hoerth, C. (2008) · Seminars in Neurology · doi:10.1055/s-2008-1062265 · Cited by 39 · see citing works
Echchannaoui, H., Frei, K., Letièmbre, M., Strieter, R. M., Adachi, Y., & Landmann, R. M. (2005) · Journal of Leukocyte Biology · doi:10.1189/jlb.0205063 · Cited by 34 · see citing works
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Hickman, S., Izzy, S., Sen, P., Morsett, L., & El Khoury, J. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0242-x · Cited by 1,710 · see citing works
Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets
Gao, C., Jiang, J., Tan, Y., & Chen, S. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01588-0 · Cited by 1,616 · see citing works
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Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
Loh, J. S., Mak, W. Q., Tan, L. K. S., Ng, C. X., Chan, H. H., Yeow, S. H., Foo, J. B., Ong, Y. S., How, C. W., & Khaw, K. Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01743-1 · Cited by 1,193 · see citing works
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Ilieva, H., Polymenidou, M., & Cleveland, D. W. (2009) · Journal of Cell Biology · doi:10.1083/jcb.200908164 · Cited by 1,008 · see citing works
Microglia polarization from M1 to M2 in neurodegenerative diseases
Guo, S., Wang, H., & Yin, Y. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.815347 · Cited by 920 · see citing works
Microglia-mediated neuroinflammation in neurodegenerative diseases
Subhramanyam, C. S., Wang, C., Hu, Q., & Dheen, S. T. (2019) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2019.05.004 · Cited by 875 · see citing works
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Kobayashi, K., Imagama, S., Ohgomori, T., Hirano, K., Uchimura, K., Sakamoto, K., Hirakawa, A., Takeuchi, H., Suzumura, A., Ishiguro, N., et al. (2013) · Cell Death & Disease · doi:10.1038/cddis.2013.54 · Cited by 742 · 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
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Jellinger, K. A. (2010) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2010.01010.x · Cited by 608 · see citing works
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Saxena, S., & Caroni, P. (2011) · Neuron · doi:10.1016/j.neuron.2011.06.031 · Cited by 561 · see citing works
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Abdel-Haq, R., Schlachetzki, J. C. M., Glass, C. K., & Mazmanian, S. K. (2019) · Journal of Experimental Medicine · doi:10.1084/jem.20180794 · Cited by 471 · see citing works
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Casula, M., Iyer, A. M., Spliet, W. G. M., Anink, J. J., Steentjes, K., Sta, M., Troost, D., & Aronica, E. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.02.001 · Cited by 200 · see citing works
Innate Immunity and Neuroinflammation
Shastri, A., Bonifati, D. M., & Kishore, U. (2013) · Mediators of Inflammation · doi:10.1155/2013/342931 · Cited by 201 · see citing works
Neurodegenerative Disease and the NLRP3 Inflammasome
Holbrook, J. A., Jarosz-Griffiths, H., Caseley, E. A., Reyna, S. J. L., Poulter, J. A., Williams‐Gray, C. H., Peckham, D. G., & McDermott, M. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.643254 · Cited by 197 · see citing works
Chen, H.-J., Anagnostou, G., Chai, A., Withers, J., Morris, A. G., Adhikaree, J., Pennetta, G., & de Belleroche, J. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.161398 · Cited by 186 · 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
The microglial-motoneuron dialogue in ALS.
Appel, S. H., Zhao, W., Beers, D. R., & Henkel-Tigges, J. (2011) · Europe PMC (PubMed Central) · Cited by 179 · see citing works
Self-citationHaslund‐Vinding, J., McBean, G., Jaquet, V, & Vilhardt, F. (2017) · British Journal of Pharmacology · doi:10.1111/bph.13425 · Cited by 169 · see citing works
Inflammation and neurovascular changes in amyotrophic lateral sclerosis
Evans, M. C., Couch, Y., Sibson, N. R., & Turner, M. R. (2012) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2012.10.008 · Cited by 174 · see citing works
IL-17A is increased in the serum and in spinal cord CD8 and mast cells of ALS patients
Fiala, M., Chattopadhay, M., Cava, A. L., Tse, E., Liu, G., Lourenço, E. V., Eskin, A., Liu, P. T., Magpantay, L. I., Tse, S., et al. (2010) · Journal of Neuroinflammation · doi:10.1186/1742-2094-7-76 · Cited by 174 · see citing works
Ravits, J., Appel, S. H., Baloh, R. H., Barohn, R. J., Brooks, B. R., Elman, L. B., Floeter, M. K., Henderson, C. E., Lomen, C. E., Macklis, J. D., et al. (2013) · Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration · doi:10.3109/21678421.2013.778548 · Cited by 168 · see citing works
Self-citationSilverman, J. M., Christy, D., Shyu, C. C., Moon, K., Fernando, S. M., Gidden, Z., Cowan, C. M., Ban, Y., Stacey, R. G., Grad, L. I., et al. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.004825 · Cited by 166 · see citing works
Innate immune activation in neurodegenerative diseases
Castro‐Gomez, S., & Heneka, M. T. (2024) · Immunity · doi:10.1016/j.immuni.2024.03.010 · Cited by 167 · see citing works
The Cu, Zn Superoxide Dismutase: Not Only a Dismutase Enzyme
Mondola, P., Damiano, S., Sasso, A., & Santillo, M. (2016) · Frontiers in Physiology · doi:10.3389/fphys.2016.00594 · Cited by 166 · see citing works
The microglial component of amyotrophic lateral sclerosis
Clarke, B. E., & Patani, R. (2020) · Brain · doi:10.1093/brain/awaa309 · Cited by 164 · 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
Non-neuronal cells in amyotrophic lateral sclerosis — from pathogenesis to biomarkers
Vahsen, B. F., Gray, E., Thompson, A. G., Ansorge, O., Anthony, D. C., Cowley, S. A., Talbot, K., & Turner, M. R. (2021) · Nature Reviews Neurology · doi:10.1038/s41582-021-00487-8 · Cited by 147 · see citing works
Pinto, S., Cunha, C., Barbosa, M., Vaz, A. R., & Brites, D. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00273 · Cited by 135 · see citing works
González, D., Contreras, O., Rebolledo, D. L., Espinoza, J. P., van Zundert, B., & Brandan, E. (2017) · PLoS ONE · doi:10.1371/journal.pone.0177649 · Cited by 129 · see citing works
Rodent models of TDP-43: Recent advances
Tsao, W., Jeong, Y. H., Lin, S. Z., Ling, J. P., Price, D. L., Chiang, P., & Wong, P. C. (2012) · Brain Research · doi:10.1016/j.brainres.2012.04.031 · Cited by 126 · 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
Tönges, L., Günther, R., Suhr, M., Jansen, J., Balck, A., Saal, K., Barski, E., Nientied, T., Götz, A. A., Koch, J., et al. (2014) · Glia · doi:10.1002/glia.22601 · Cited by 121 · see citing works
Trudler, D., Farfara, D., & Frenkel, D. (2010) · Mediators of Inflammation · doi:10.1155/2010/497987 · Cited by 117 · 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
Rojas, F., Cortés, N., Abarzúa, S., Dyrda, A., & van Zundert, B. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00024 · Cited by 112 · see citing works
Toll‐like receptors in neuroinflammation, neurodegeneration, and alcohol‐induced brain damage
Pascual, M., Calvo-Rodríguez, M., Núñez, L., Villalobos, C., Ureña, J., & Guerri, C. (2021) · IUBMB Life · doi:10.1002/iub.2510 · Cited by 114 · see citing works
Amyotrophic Lateral Sclerosis: A Neurodegenerative Motor Neuron Disease With Ocular Involvement
Rojas, P., Ramirez, A. I., Fernández‐Albarral, J. A., López‐Cuenca, I., Salobrar‐García, E., Cadena, M., Elvira‐Hurtado, L., Salazar, J. J., de Hoz, R., & Ramirez, J. M. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.566858 · Cited by 116 · see citing works
Glial Cells in Amyotrophic Lateral Sclerosis
Lasiene, J., & Yamanaka, K. (2011) · Neurology Research International · doi:10.1155/2011/718987 · Cited by 110 · see citing works
The role of the immune system in neurodegenerative disorders: Adaptive or maladaptive?
Doty, K. R., Guillot-Sestier, M.-V., & Town, T. (2015) · Brain Research · doi:10.1016/j.brainres.2014.09.008 · Cited by 104 · see citing works
Astrocyte–neuron interplay in maladaptive plasticity.
Papa, M., De Luca, C., Petta, F., Alberghina, L., & Cirillo, G. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.01.010 · Cited by 104 · see citing works
Smith, S. M. C., Friedle, S. A., & Watters, J. J. (2013) · PLoS ONE · doi:10.1371/journal.pone.0081584 · Cited by 106 · see citing works
Roberts, K., Zeineddine, R., Corcoran, L., Li, W., Campbell, I. L., & Yerbury, J. J. (2012) · Glia · doi:10.1002/glia.22444 · Cited by 102 · see citing works
Non‐neuronal Cells in ALS: Role of Glial, Immune cells and Blood‐CNS Barriers
Puentes, F., Malaspina, A., van Noort, J. M., & Amor, S. (2016) · Brain Pathology · doi:10.1111/bpa.12352 · Cited by 98 · see citing works
Figueroa-Romero, C., Guo, K., Murdock, B. J., Paez-Colasante, X., Bassis, C. M., Mikhail, K. A., Raue, K. D., Evans, M. C., Taubman, G. F., McDermott, A. J., et al. (2019) · Disease Models & Mechanisms · doi:10.1242/dmm.041947 · Cited by 94 · see citing works
Cellular therapy to target neuroinflammation in amyotrophic lateral sclerosis
Rizzo, F., Riboldi, G. M., Salani, S., Nizzardo, M., Simone, C., Corti, S. P., & Hedlund, E. (2013) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-013-1480-4 · Cited by 93 · see citing works
Calabrese, G., Molzahn, C. M., & Mayor, T. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.102062 · Cited by 90 · see citing works
Disease origin and progression in amyotrophic lateral sclerosis: an immunology perspective
Malaspina, A., Puentes, F., & Amor, S. (2014) · International Immunology · doi:10.1093/intimm/dxu099 · Cited by 90 · see citing works
Phytochemicals against TNFα-Mediated Neuroinflammatory Diseases
Subedi, L., Lee, S. E., Madiha, S., Gaire, B. P., Jin, M., Yumnam, S., & Kim, S. Y. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21030764 · Cited by 93 · see citing works
Interplay Between Exosomes, microRNAs and Toll-Like Receptors in Brain Disorders
Paschon, V., Takada, S. H., Ikebara, J. M., de Sousa, É., Raeisossadati, R., Ulrich, H., & Kihara, A. H. (2015) · Molecular Neurobiology · doi:10.1007/s12035-015-9142-1 · Cited by 91 · see citing works
Neuroinflammation in motor neuron disease
Endo, F., Komine, O., & Yamanaka, K. (2016) · Clinical and Experimental Neuroimmunology · doi:10.1111/cen3.12309 · Cited by 93 · see citing works
Toll-like receptors in central nervous system injury and disease: A focus on the spinal cord
Heiman, A., Pallottie, A., Heary, R. F., & Elkabes, S. (2014) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2014.06.203 · Cited by 91 · see citing works
Inflammation, Immunity, and amyotrophic lateral sclerosis: I. Etiology and pathology
Lyon, M. S., Wosiski‐Kuhn, M., Gillespie, R., Caress, J. B., & Milligan, C. (2018) · Muscle & Nerve · doi:10.1002/mus.26289 · Cited by 88 · see citing works
Key Mechanisms and Potential Targets of the NLRP3 Inflammasome in Neurodegenerative Diseases
Guan, Y., & Han, F. (2020) · Frontiers in Integrative Neuroscience · doi:10.3389/fnint.2020.00037 · Cited by 87 · see citing works
Neuroinflammation in motor neuron disease.
Komine, O., & Yamanaka, K. (2015) · Europe PMC (PubMed Central) · doi:10.18999/nagjms.77.4.537 · Cited by 87 · see citing works
The neurobiology of amyotrophic lateral sclerosis
Bento‐Abreu, A., Damme, P. V., Bosch, L. V. D., & Robberecht, W. (2010) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2010.07260.x · Cited by 85 · see citing works
Can we switch microglia's phenotype to foster neuroprotection? Focus on multiple sclerosis
Giunti, D., Parodi, B., Cordano, C., Uccelli, A., & de Rosbo, N. K. (2013) · Immunology · doi:10.1111/imm.12177 · Cited by 85 · see citing works
A rat model of ataxia-telangiectasia: evidence for a neurodegenerative phenotype
Quek, H., Luff, J., Cheung, K., Kozlov, S., Gatei, M. H., Lee, C. S., Bellingham, M. C., Noakes, P. G., Lim, Y. C., Barnett, N. L., et al. (2016) · Human Molecular Genetics · doi:10.1093/hmg/ddw371 · Cited by 80 · see citing works
Early pathogenesis in the adult‐onset neurodegenerative disease amyotrophic lateral sclerosis
van Zundert, B., Izaurieta, P., Fritz, E., & Álvarez, F. J. (2012) · Journal of Cellular Biochemistry · doi:10.1002/jcb.24234 · Cited by 80 · see citing works
Glial Cells—The Strategic Targets in Amyotrophic Lateral Sclerosis Treatment
Filipi, T., Heřmanová, Z., Turečková, J., Vaňátko, O., & Anděrová, M. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9010261 · Cited by 74 · see citing works
The dual roles of immunity in ALS: Injury overrides protection
Murdock, B. J., Bender, D. E., Segal, B. M., & Feldman, E. L. (2015) · Neurobiology of Disease · doi:10.1016/j.nbd.2015.02.017 · Cited by 73 · see citing works
Bellezza, I., Grottelli, S., Costanzi, E., Scarpelli, P. T., Pigna, E., Morozzi, G., Mezzasoma, L., Peirce, M. J., Moresi, V., Adamo, S., et al. (2017) · Molecular Neurobiology · doi:10.1007/s12035-017-0502-x · Cited by 73 · see citing works
Stem Cell Transplantation for Motor Neuron Disease: Current Approaches and Future Perspectives
Gowing, G., & Svendsen, C. N. (2011) · Neurotherapeutics · doi:10.1007/s13311-011-0068-7 · Cited by 70 · see citing works
Inflammation and neurodegeneration: the story ‘retolled’
Drouin‐Ouellet, J., & Cicchetti, F. (2012) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2012.07.002 · Cited by 70 · see citing works
Retromer stabilization results in neuroprotection in a model of Amyotrophic Lateral Sclerosis
Muzio, L., Sirtori, R., Gornati, D., Eleuteri, S., Fossaghi, A., Brancaccio, D., Manzoni, L., Ottoboni, L., Feo, L. D., Quattrini, A., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-17524-7 · Cited by 64 · see citing works
Misfolded superoxide dismutase‐1 in CSF from amyotrophic lateral sclerosis patients
Zetterström, P., Andersen, P. M., Brännström, T., & Marklund, S. L. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07177.x · Cited by 67 · see citing works
Garbuzova-Davis, S. N., Rodrigues, M. C. O., Mirtyl, S., Turner, S., Mitha, S. A., Sodhi, J., Suthakaran, S., Eve, D. J., Sanberg, C. D., Kuzmin‐Nichols, N., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0031254 · Cited by 66 · see citing works
Cozzolino, M., Pesaresi, M. G., Gerbino, V., Großkreutz, J., & Carrı̀, M. T. (2012) · Antioxidants and Redox Signaling · doi:10.1089/ars.2011.4328 · Cited by 65 · see citing works
Dibaj, P., Steffens, H., Zschüntzsch, J., Nadrigny, F., Schomburg, E. D., Kirchhoff, F., & Neusch, C. (2011) · PLoS ONE · doi:10.1371/journal.pone.0017910 · Cited by 63 · see citing works
Matamala, J. M., Arias‐Carrasco, R., Sanchez, C., Uhrig, M., Bargsted, L., Matus, S., Maracaja‐Coutinho, V., Abarzúa, S., van Zundert, B., Verdugo, R. J., et al. (2017) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2017.12.020 · Cited by 63 · see citing works
Nicaise, C., Mitrečić, D., & Pochet, R. (2010) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2010.01124.x · Cited by 62 · see citing works
Role of Toll-like receptor/MYD88 signaling in neurodegenerative diseases
Xiang, W., Chao, Z.-Y., & Feng, D.-Y. (2015) · Reviews in the Neurosciences · doi:10.1515/revneuro-2014-0067 · Cited by 62 · see citing works
Komine, O., Yamashita, H., Fujimori-Tonou, N., Koike, M., Jin, S., Moriwaki, Y., Endo, F., Watanabe, S., Uematsu, S., Akira, S., et al. (2018) · Cell Death and Differentiation · doi:10.1038/s41418-018-0098-3 · Cited by 61 · see citing works
Paola, M. D., Sestito, S. E., Mariani, A., Memo, C., Fanelli, R., Freschi, M., Bendotti, C., Calabrese, V., & Peri, F. (2015) · Pharmacological Research · doi:10.1016/j.phrs.2015.11.020 · Cited by 58 · see citing works
Genetic manipulation of microglia during brain development and disease
Wieghofer, P., & Prinz, M. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.09.019 · Cited by 58 · see citing works
Vitamin D as a Potential Therapy in Amyotrophic Lateral Sclerosis
Gianforcaro, A., & Hamadeh, M. J. (2014) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.12204 · Cited by 57 · see citing works
Fragment C of tetanus toxin, more than a carrier. Novel perspectives in non-viral ALS gene therapy
Moreno‐Igoa, M., Calvo, A. C., Penas, C., Manzano, R., Oliván, S., Muñoz, M. J., Mancuso, R., Zaragoza, P., Aguilera, J., Navarro, X., et al. (2009) · Journal of Molecular Medicine · doi:10.1007/s00109-009-0556-y · Cited by 55 · see citing works
Vaz, A. R., Pinto, S., Ezequiel, C., Cunha, C., Carvalho, L. A., Moreira, R., & Brites, D. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00109 · Cited by 55 · see citing works
Interplay between immunity and amyotrophic lateral sclerosis: Clinical impact
Marchi, F. D., Munitić, I., Amedei, A., Berry, J. D., Feldman, E. L., Aronica, E., Nardo, G., Weehaeghe, D. V., Niccolai, E., Prtenjača, N., et al. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.06.027 · Cited by 52 · see citing works
- Authors
- Zhao, W., Beers, D. R., Henkel, J. S., Zhang, W., Urushitani, M., Julien, J., & Appel, S. H.
- Affiliations
- Houston Methodist (US)
- Shiga University of Medical Science (JP)
- Université Laval (CA)
- Corresponding author
- Appel, Stanley H.
- Venue
- Glia
- Publisher
- Wiley
- Published
- 2009-08-11
- Volume
- 58
- Issue
- 2
- Pages
- 231-243
- ISSN
- 0894-1491 (ISSN-L)
- 1098-1136
- PMC
- PMC2784168
- OpenAlex
- W2066874059
- Cited by
- 288
- References
- 51
- Citations by year
- 2026: 8 · 2025: 16 · 2024: 15 · 2023: 12 · 2022: 13 · 2021: 19 · 2020: 21 · 2019: 13 · 2018: 15 · 2017: 19 · 2016: 18 · 2015: 16 · 2014: 16 · 2013: 23 · 2012: 24
- FWCI
- 13.61
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Glia (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS048950, R01NS048950)
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- amyotrophic lateral sclerosis, SOD1 mutations, microglial activation, non-cell autonomous neurodegeneration, CD14, Toll-like receptors, TLR2, TLR4, inflammatory cytokines, free radicals, innate immunity, SOD1 G93A
- MeSH terms
- Superoxide Dismutase-1, Animals, Cells, Cultured, Extracellular Space, Humans, Mice, Inbred C57BL, Mice, Transgenic, Motor Neurons, Recombinant Proteins, Spinal Cord, Superoxide Dismutase, Signal Transduction, Cell Death, Microglia, Mice, Knockout, Coculture Techniques, Lipopolysaccharide Receptors, Mutation, Missense, Toll-Like Receptor 2, Toll-Like Receptor 4, Mice
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