Knockout of reactive astrocyte activating factors slows disease progression in an ALS mouse model
Open accessAbstract
Reactive astrocytes have been implicated in the pathogenesis of neurodegenerative diseases, including a non-cell autonomous effect on motor neuron survival in ALS. We previously defined a mechanism by which microglia release three factors, IL-1α, TNFα, and C1q, to induce neurotoxic astrocytes. Here we report that knocking out these three factors markedly extends survival in the SOD1 G93A ALS mouse model, providing evidence for gliosis as a potential ALS therapeutic target.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Genomic deletion of Il1a, Tnf, and C1qa extended the lifespan of SOD1G93A ALS model mice.
“and extended the lifespan of SOD1G93A ALS model mice4.”
From Neurotoxic reactive astrocytes induce cell death via saturated lipids (2021) · cites this paper as [4]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106 · see citing works
STAR: ultrafast universal RNA-seq aligner
Dobin, A., Davis, C. A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., & Gingeras, T. R. (2013) · Bioinformatics · doi:10.1093/bioinformatics/bts635 · Cited by 51,709 · see citing works
Neurotoxic reactive astrocytes are induced by activated microglia
Liddelow, S. A., Guttenplan, K. A., Clarke, L. E., Bennett, F. C., Bohlen, C. J., Schirmer, L., Bennett, M. L., Münch, A. E., Chung, W.-S., Peterson, T. C., et al. (2017) · Nature · doi:10.1038/nature21029 · Cited by 7,971 · see citing works
Self-citationMotor 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
Decoding ALS: from genes to mechanism
Taylor, J. P., Brown, R. H., & Cleveland, D. W. (2016) · Nature · doi:10.1038/nature20413 · Cited by 2,117 · see citing works
New tools for studying microglia in the mouse and human CNS
Bennett, M. L., Bennett, F. C., Liddelow, S. A., Ajami, B., Zamanian, J. L., Fernhoff, N. B., Mulinyawe, S. B., Bohlen, C. J., Adil, A., Tucker, A., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1525528113 · Cited by 1,804 · see citing works
Self-citationOnset 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
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
Normal aging induces A1-like astrocyte reactivity
Clarke, L. E., Liddelow, S. A., Chakraborty, C., Münch, A. E., Heiman, M., & Barres, B. A. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1800165115 · Cited by 1,237 · see citing works
Self-citationAstrocytes 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
ApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy
Initiative, A. D. N., Shi, Y., Yamada, K., Liddelow, S. A., Smith, S. T., Zhao, L., Luo, W., Tsai, R. M., Spina, S., Grinberg, L. T., et al. (2017) · Nature · doi:10.1038/nature24016 · Cited by 1,220 · see citing works
Self-citationBlock of A1 astrocyte conversion by microglia is neuroprotective in models of Parkinson’s disease
Yun, S. P., Kam, T.-I., Panicker, N., Kim, S., Oh, Y., Park, J.-S., Kwon, S.-H., Park, Y. J., Karuppagounder, S. S., Park, H., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0051-5 · Cited by 1,123 · see citing works
Self-citationWild-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
Non–cell autonomous toxicity in neurodegenerative disorders: ALS and beyond
Ilieva, H., Polymenidou, M., & Cleveland, D. W. (2009) · Journal of Cell Biology · doi:10.1083/jcb.200908164 · Cited by 1,008 · see citing works
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
Astrocytes 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
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
The aging astrocyte transcriptome from multiple regions of the mouse brain.
Boisvert, M. M., Erikson, G. A., Shokhirev, M. N., & Allen, N. J. (2018) · Cell Reports · doi:10.1016/j.celrep.2017.12.039 · Cited by 702 · see citing works
Bohlen, C. J., Bennett, F. C., Tucker, A. F., Collins, H. Y., Mulinyawe, S. B., & Barres, B. A. (2017) · Neuron · doi:10.1016/j.neuron.2017.04.043 · Cited by 676 · see citing works
Self-citationMicroglia 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
Miller, T. M., Pestronk, A., David, W., Rothstein, J., Simpson, E., Appel, S. H., Andres, P. L., Mahoney, K., Allred, P., Alexander, K., et al. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70061-9 · Cited by 617 · see citing works
Kang, S. H., Li, Y., Fukaya, M., Lorenzini, I., Cleveland, D. W., Ostrow, L. W., Rothstein, J. D., & Bergles, D. E. (2013) · Nature Neuroscience · doi:10.1038/nn.3357 · Cited by 599 · see citing works
Joshi, A. U., Minhas, P. S., Liddelow, S. A., Haileselassie, B., Andreasson, K. I., Dorn, G. W., & Mochly-Rosen, D. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0486-0 · Cited by 571 · see citing works
Self-citationAntisense oligonucleotide therapy for neurodegenerative disease
Smith, R. A. (2006) · Journal of Clinical Investigation · doi:10.1172/jci25424 · Cited by 506 · see citing works
Development of a Method for the Purification and Culture of Rodent Astrocytes
Foo, L. C., Allen, N. J., Bushong, E. A., Ventura, P. B., Chung, W.-S., Zhou, L., Cahoy, J. D., Daneman, R., Zong, H., Ellisman, M. H., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.07.022 · Cited by 433 · see citing works
Self-citationReactive astrocytes secrete lcn2 to promote neuron death
Bi, F., Huang, C., Tong, J., Qiu, G., Huang, B., Wu, Q., Li, F., Xu, Z., Bowser, R., Xia, X.-G., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1218497110 · Cited by 371 · 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
Antisense oligonucleotides extend survival and reverse decrement in muscle response in ALS models
McCampbell, A., Cole, T., Wegener, A. J., Tomassy, G. S., Setnicka, A., Farley, B. J., Schoch, K. M., Hoye, M. L., Shabsovich, M., Sun, L., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci99081 · Cited by 279 · see citing works
Neurotoxic Reactive Astrocytes Drive Neuronal Death after Retinal Injury
Guttenplan, K. A., Stafford, B. K., El-Danaf, R. N., Adler, D. I., Münch, A. E., Weigel, M. K., Huberman, A. D., & Liddelow, S. A. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107776 · Cited by 221 · see citing works
Self-citationSun, S., Sun, Y., Ling, S., Ferraiuolo, L., McAlonis‐Downes, M., Zou, Y., Drenner, K., Wang, Y., Ditsworth, D., Tokunaga, S., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1520639112 · Cited by 194 · see citing works
Astrocyte loss of mutant SOD1 delays ALS disease onset and progression in G85R transgenic mice
Wang, L., Gutmann, D. H., & Roos, R. P. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq463 · Cited by 192 · see citing works
Oligodendrocytes contribute to motor neuron death in ALS via SOD1-dependent mechanism
Ferraiuolo, L., Meyer, K., Sherwood, T. W., Vick, J. S., Likhite, S. B., Frakes, A., Miranda, C. J., Braun, L., Heath, P. R., Pineda, R., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1607496113 · Cited by 189 · see citing works
Astrocytes and microglia: Models and tools
Guttenplan, K. A., & Liddelow, S. A. (2018) · The Journal of Experimental Medicine · doi:10.1084/jem.20180200 · Cited by 156 · 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
Wang, L., Sharma, K., Grisotti, G., & Roos, R. P. (2009) · Neurobiology of Disease · doi:10.1016/j.nbd.2009.05.002 · Cited by 114 · 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
Lobsiger, C. S., Boillée, S., Pozniak, C. D., Khan, A. M., McAlonis‐Downes, M., Lewcock, J. W., & Cleveland, D. W. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1318309110 · Cited by 72 · see citing works
Han, Y., Ripley, B., Serada, S., Naka, T., & Fujimoto, M. (2016) · PLoS ONE · doi:10.1371/journal.pone.0153399 · Cited by 24 · see citing works
Is TNF inhibitor exposure a risk factor for amyotrophic lateral sclerosis?
Petitpain, N., Devos, D., Bagheri, H., et al. (2019) · Fundamental and Clinical Pharmacology · doi:10.1111/fcp.12480 · Cited by 9 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Neuroinflammation in neurodegenerative disorders: the roles of microglia and astrocytes
Kwon, H. S., & Koh, S.-H. (2020) · Translational Neurodegeneration · doi:10.1186/s40035-020-00221-2 · Cited by 2,595 · see citing works
Neurotoxic reactive astrocytes induce cell death via saturated lipids
Guttenplan, K. A., Weigel, M. K., Prakash, P., Wijewardhane, P. R., Hasel, P., Rufen-Blanchette, U., Münch, A. E., Blum, J. A., Fine, J., Neal, M. C., et al. (2021) · Nature · doi:10.1038/s41586-021-03960-y · Cited by 578 · see citing works
Self-citationAstrocyte contribution to dysfunction, risk and progression in neurodegenerative disorders
Brandebura, A. N., Paumier, A., Onur, T. S., & Allen, N. J. (2023) · Nature Reviews Neuroscience · doi:10.1038/s41583-022-00641-1 · Cited by 427 · see citing works
Sadick, J. S., O’Dea, M. R., Hasel, P., Dykstra, T., Faustin, A., & Liddelow, S. A. (2022) · Neuron · doi:10.1016/j.neuron.2022.03.008 · Cited by 415 · see citing works
Self-citationMorphological, cellular and molecular basis of brain infection in COVID-19 patients
Crunfli, F., Carregari, V. C., Veras, F. P., Vendramini, P. H., Valença, A. G. F., Antunes, A. S. L. M., Brandão-Teles, C., da Silva Zuccoli, G., Reis-de-Oliveira, G., Silva-Costa, L. C., et al. (2020) · doi:10.1101/2020.10.09.20207464 · Cited by 331 · see citing works
Humphrey, J., Venkatesh, S., Hasan, R., Herb, J. T., de Paiva Lopes, K., Küçükali, F., Byrska-Bishop, M., Evani, U. S., Narzisi, G., Fagegaltier, D., et al. (2023) · Nature Neuroscience · doi:10.1038/s41593-022-01205-3 · Cited by 138 · see citing works
The contribution of the peripheral immune system to neurodegeneration
Berriat, F., Lobsiger, C. S., & Boillée, S. (2023) · Nature Neuroscience · doi:10.1038/s41593-023-01323-6 · Cited by 87 · see citing works
What are activated and reactive glia and what is their role in neurodegeneration?
Bennett, M. L., & Viaene, A. N. (2021) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.105172 · Cited by 77 · see citing works
Mitochondrial dysfunction compromises ciliary homeostasis in astrocytes
Ignatenko, O., Malinen, S., Rybas, S., Vihinen, H., Nikkanen, J., Kononov, A., Jokitalo, E. S., Ince-Dunn, G., & Suomalainen, A. (2023) · Journal of Cell Biology · doi:10.1083/jcb.202203019 · Cited by 63 · see citing works
The role of immune-mediated alterations and disorders in ALS disease
Rodrigues Lima-Junior, J., Sulzer, D., Lindestam Arlehamn, C. S., & Sette, A. (2021) · Human Immunology · doi:10.1016/j.humimm.2021.01.017 · Cited by 33 · see citing works
Context‐dependent roles of cellular senescence in normal, aged, and disease states
Moiseeva, V., Cisneros, A., Cobos, A. C., Tarrega, A. B., Oñate, C. S., Perdiguero, E., Serrano, A. L., & Muñoz‐Cánoves, P. (2023) · The FEBS Journal · doi:10.1111/febs.16573 · Cited by 34 · see citing works
Co-Culture Models: Key Players in In Vitro Neurotoxicity, Neurodegeneration and BBB Modeling Studies
Monteiro, A. R., Barbosa, D. J., Remião, F., & Silva, R. (2024) · Biomedicines · doi:10.3390/biomedicines12030626 · Cited by 27 · see citing works
Depletion of Microglia Increases Cortical Oligodendrocyte Density During Remyelination
Loo, H. K., Gallegos, J., Mialki, C., Perrin, G. E., Malloy, T., & Orthmann‐Murphy, J. L. (2026) · Glia · doi:10.1002/glia.70120 · Cited by 2 · see citing works
- Authors
- Guttenplan, K. A., Weigel, M. K., Adler, D. I., Couthouis, J., Liddelow, S. A., Gitler, A. D., & Barres, B. A.
- Affiliations
- Stanford Medicine (US)
- NYU Langone Health (US)
- Stanford University (US)
- Corresponding author
- Guttenplan, Kevin A.
- Gitler, Aaron D.
- ORCID
- Venue
- Nature Communications
- Published
- 2020-07-27
- Volume
- 11
- Issue
- 1
- Pages
- 3753-3753
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC7385161
- OpenAlex
- W3044057346
- Cited by
- 278
- References
- 39
- Citations by year
- 2026: 32 · 2025: 43 · 2024: 54 · 2023: 53 · 2022: 53 · 2021: 37 · 2020: 6
- FWCI
- 16.12
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (R35NS097263)
- 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, reactive astrocytes, gliosis, microglia, IL-1α, TNF-α, C1q, SOD1 G93A mouse model, gene knockout, disease progression, motor neuron survival, neuroinflammation
- MeSH terms
- Superoxide Dismutase-1, Amyotrophic Lateral Sclerosis, Animals, Astrocytes, Complement C3, Disease Models, Animal, Humans, Mice, Inbred C57BL, Tumor Necrosis Factor-alpha, Complement C1q, Microglia, Mice, Knockout, Disease Progression, Interleukin-1alpha
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
