Cited by 1,220Amyotrophic Lateral Sclerosis ResearchAlzheimer's disease research and treatmentsHereditary Neurological Disorders

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Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons

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Nagai, Makiko, Re, Diane B, Nagata, Tetsuya, Chalazonitis, Alcmène, Jessell, Thomas M, Wichterle, Hynek, Przedborski, Serge·2007·Nature Neuroscience

DOI 10.1038/nn1876PMC PMC3799799

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Abstract

Mutations in superoxide dismutase-1 (SOD1) cause a form of the fatal paralytic disorder amyotrophic lateral sclerosis (ALS), presumably by a combination of cell-autonomous and non-cell-autonomous processes. Here, we show that expression of mutated human SOD1 in primary mouse spinal motor neurons does not provoke motor neuron degeneration. Conversely, rodent astrocytes expressing mutated SOD1 kill spinal primary and embryonic mouse stem cell-derived motor neurons. This is triggered by soluble toxic factor(s) through a Bax-dependent mechanism. However, mutant astrocytes do not cause the death of spinal GABAergic or dorsal root ganglion neurons or of embryonic stem cell-derived interneurons. In contrast to astrocytes, fibroblasts, microglia, cortical neurons and myocytes expressing mutated SOD1 do not cause overt neurotoxicity. These findings indicate that astrocytes may play a role in the specific degeneration of spinal motor neurons in ALS. Identification of the astrocyte-derived soluble factor(s) may have far-reaching implications for ALS from both a pathogenic and therapeutic standpoint.

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Cytoprotective membrane-permeable peptides designed from the Bax-binding domain of Ku70
Sawada, M., Hayes, P. L., & Matsuyama, S. (2003) · Nature Cell Biology · doi:10.1038/ncb955 · Cited by 162
Retracted
Copper-Zinc Superoxide Dismutase (SOD1) Is Released by Microglial Cells and Confers Neuroprotection against 6-OHDA Neurotoxicity
Polazzi, E., Mengoni, I., Caprini, M., Peña‐Altamira, E., Kurtys, E., & Monti, B. (2012) · Neurosignals · doi:10.1159/000337115 · Cited by 9,023
Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis
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
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
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
Self-citation
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
Amyotrophic Lateral Ssclerosis and Structural Defects in Cu,Zn Superoxide Dismutase
Deng, H., Hentati, A., Tainer, J. A., Iqbal, Z., Cayabyab, A., Hung, W.-Y., Getzoff, E. D., Hu, P., Herzfeldt, B., Roos, R. P., et al. (1993) · Science · doi:10.1126/science.8351519 · Cited by 1,479
An adverse property of a familial ALS-linked SOD1 mutation causes motor neuron disease characterized by vacuolar degeneration of mitochondria
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
ALS-Linked SOD1 Mutant G85R Mediates Damage to Astrocytes and Promotes Rapidly Progressive Disease with SOD1-Containing Inclusions
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
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 1,131

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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
An RNA-Sequencing Transcriptome and Splicing Database of Glia, Neurons, and Vascular Cells of the Cerebral Cortex
Zhang, Y., Chen, K., Sloan, S. A., Bennett, M. L., Scholze, A. R., O'Keeffe, S., Phatnani, H. P., Guarnieri, P., Caneda, C., Ruderisch, N., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.1860-14.2014 · Cited by 4,875
“…spectrum disorders, epilepsy, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, and stroke (Matute et al., 2005; Tian et al., 2005; Nagai et al., 2007; Chen et al., 2009; Li et al., 2011; Lioy et al., 2011; Molofsky et al., 2012; Zamanian et al., 2012).”
Background
Astrocytes: Biology and pathology
Sofroniew, M. V., & Vinters, H. V. (2010) · Acta Neuropathologica · doi:10.1007/s00401-009-0619-8 · Cited by 5,196
The Blood-Brain Barrier in Health and Chronic Neurodegenerative Disorders
Zlokovic, B. V. (2008) · Neuron · doi:10.1016/j.neuron.2008.01.003 · Cited by 3,280
Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders
Zlokovic, B. V. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn3114 · Cited by 2,969
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
Molecular dissection of reactive astrogliosis and glial scar formation
Sofroniew, M. V. (2009) · Trends in Neurosciences · doi:10.1016/j.tins.2009.08.002 · Cited by 2,594
Reactive Astrocytes: Production, Function, and Therapeutic Potential
Liddelow, S. A., & Barres, B. A. (2017) · Immunity · doi:10.1016/j.immuni.2017.06.006 · Cited by 2,336
Decoding ALS: from genes to mechanism
Taylor, J. P., Brown, R. H., & Cleveland, D. W. (2016) · Nature · doi:10.1038/nature20413 · Cited by 2,120
Induced Pluripotent Stem Cells Generated from Patients with ALS Can Be Differentiated into Motor Neurons
Dimos, J. T., Rodolfa, K. T., Niakan, K. K., Weisenthal, L. M., Mitsumoto, H., Chung, W. K., Croft, G. F., Saphier, G., Leibel, R. L., Goland, R., et al. (2008) · Science · doi:10.1126/science.1158799 · Cited by 2,019
Self-citation
The Science of Stroke: Mechanisms in Search of Treatments
Moskowitz, M. A., Lo, E. H., & Iadecola, C. (2010) · Neuron · doi:10.1016/j.neuron.2010.07.002 · Cited by 1,930
Converging Mechanisms in ALS and FTD: Disrupted RNA and Protein Homeostasis
Ling, S.-C., Polymenidou, M., & Cleveland, D. W. (2013) · Neuron · doi:10.1016/j.neuron.2013.07.033 · Cited by 1,811
PINK1-dependent recruitment of Parkin to mitochondria in mitophagy
Vives-Bauza, C., Zhou, C., Huang, Y., Cui, M., de Vries, R. L. A., Kim, J., May, J., Tocilescu, M. A., Liu, W., Ko, H. S., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0911187107 · Cited by 1,616
Self-citation
Induced pluripotent stem cell technology: a decade of progress.
Shi, Y., Inoue, H., Wu, J. C., & Yamanaka, S. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.245 · Cited by 1,525
Transfer of mitochondria from astrocytes to neurons after stroke
Hayakawa, K., Esposito, E., Wang, X., Terasaki, Y., Liu, Y., Xing, C., Ji, X., & Lo, E. H. (2016) · Nature · doi:10.1038/nature18928 · Cited by 1,423
The Mystery and Magic of Glia: A Perspective on Their Roles in Health and Disease
Barres, B. A. (2008) · Neuron · doi:10.1016/j.neuron.2008.10.013 · Cited by 1,352
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
Astrocyte barriers to neurotoxic inflammation
Sofroniew, M. V. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3898 · Cited by 1,202
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
GFAP in health and disease
Middeldorp, J., & Hol, E. M. (2011) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2011.01.005 · Cited by 1,080
NAD+ metabolism: pathophysiologic mechanisms and therapeutic potential
Xie, N., Zhang, L., Gao, W. Q., Huang, C., Huber, P., Zhou, X., Li, C. L., Shen, G., & Zou, B. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00311-7 · Cited by 1,147
Astrocyte reactivity and reactive astrogliosis: costs and benefits
Pekny, M., & Pekna, M. (2014) · Physiological Reviews · doi:10.1152/physrev.00041.2013 · Cited by 934
Oxidative Stress in Neurodegenerative Diseases: From Molecular Mechanisms to Clinical Applications
Liu, Z., Zhou, T., Ziegler, A. C., Dimitrion, P., & Zuo, L. (2017) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2017/2525967 · Cited by 810
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
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
Minocycline selectively inhibits M1 polarization of microglia
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
A comprehensive review on emerging artificial neuromorphic devices
Zhu, J., Zhang, T., Yang, Y., & Huang, R. (2020) · Applied Physics Reviews · doi:10.1063/1.5118217 · Cited by 783
Developmental genetics of vertebrate glial–cell specification
Rowitch, D. H., & Kriegstein, A. R. (2010) · Nature · doi:10.1038/nature09611 · Cited by 774
Astrogliosis
Sofroniew, M. V. (2015) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a020420 · Cited by 695
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
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
Astrocyte–neuron metabolic relationships: for better and for worse
Allaman, I., Bélanger, M., & Magistretti, P. J. (2011) · Trends in Neurosciences · doi:10.1016/j.tins.2010.12.001 · Cited by 639
The glia/neuron ratio: How it varies uniformly across brain structures and species and what that means for brain physiology and evolution
Herculano‐Houzel, S. (2014) · Glia · doi:10.1002/glia.22683 · Cited by 731
Conversion of Mouse and Human Fibroblasts into Functional Spinal Motor Neurons
Son, E., Ichida, J. K., Wainger, B. J., Toma, J. S., Rafuse, V. F., Woolf, C. J., & Eggan, K. C. (2011) · Cell stem cell · doi:10.1016/j.stem.2011.07.014 · Cited by 651
Oxidative stress in ALS: Key role in motor neuron injury and therapeutic target
Barber, S. C., & Shaw, P. J. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.11.018 · Cited by 647
Molecular pathways of motor neuron injury in amyotrophic lateral sclerosis
Ferraiuolo, L., Kirby, J., Grierson, A. J., Sendtner, M., & Shaw, P. J. (2011) · Nature Reviews Neurology · doi:10.1038/nrneurol.2011.152 · Cited by 615
Microglia and Central Nervous System–Associated Macrophages—From Origin to Disease Modulation
Prinz, M., Masuda, T., Wheeler, M. A., & Quintana, F. J. (2021) · Annual Review of Immunology · doi:10.1146/annurev-immunol-093019-110159 · Cited by 584
ALS motor phenotype heterogeneity, focality, and spread
Ravits, J., & Spada, A. R. L. (2009) · Neurology · doi:10.1212/wnl.0b013e3181b6bbbd · Cited by 629
Basic mechanisms of neurodegeneration: a critical update
Jellinger, K. A. (2010) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2010.01010.x · Cited by 640
Degeneration and impaired regeneration of gray matter oligodendrocytes in amyotrophic lateral sclerosis
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
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
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
Lithium delays progression of amyotrophic lateral sclerosis
Fornai, F., Longone, P., Cafaro, L., Kastsiuchenka, O., Ferrucci, M., Manca, M. L., Lazzeri, G., Spalloni, A., Bellio, N., Lenzi, P., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0708022105 · Cited by 550
Functional roles of reactive astrocytes in neuroinflammation and neurodegeneration
Patani, R., Hardingham, G. E., & Liddelow, S. A. (2023) · Nature Reviews Neurology · doi:10.1038/s41582-023-00822-1 · Cited by 531
Intravenous administration of self-complementary AAV9 enables transgene delivery to adult motor neurons
Duque, S., Joussemet, B., Riviere, C., Marais, T., Dubreil, L., Douar, A.-M., Fyfe, J., Moullier, P., Colle, M.-A., & Barkats, M. (2009) · Molecular Therapy · doi:10.1038/mt.2009.71 · Cited by 511
Transgenics, toxicity and therapeutics in rodent models of mutant SOD1-mediated familial ALS
Turner, B. J., & Talbot, K. (2008) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2008.01.001 · Cited by 524
The Transcriptome and Metabolic Gene Signature of Protoplasmic Astrocytes in the Adult Murine Cortex
Lovatt, D., Sonnewald, U., Waagepetersen, H. S., Schousboe, A., He, W., Lin, J. H.-C., Han, X., Takano, T., Wang, S., Sim, F. J., et al. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.3404-07.2007 · Cited by 505
Human Embryonic Stem Cell-Derived Motor Neurons Are Sensitive to the Toxic Effect of Glial Cells Carrying an ALS-Causing Mutation
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
Nrf2 Activation in Astrocytes Protects against Neurodegeneration in Mouse Models of Familial Amyotrophic Lateral Sclerosis
Vargas, M. R., Johnson, D. A., Sirkis, D. W., Messing, A., & Johnson, J. A. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.4099-08.2008 · Cited by 479
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
Generation and expansion of highly pure motor neuron progenitors from human pluripotent stem cells
Du, Z., Chen, H., Liu, H., Lü, J., Qian, K. X., Huang, C., Zhong, X., Fan, F., & Zhang, S. (2015) · Nature Communications · doi:10.1038/ncomms7626 · Cited by 471
Non-Cell-Autonomous Effect of Human SOD1G37R Astrocytes on Motor Neurons Derived from Human Embryonic Stem Cells
Marchetto, M. C. N., 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 475
Focal transplantation–based astrocyte replacement is neuroprotective in a model of motor neuron disease
Lepore, A. C., Rauck, B., Dejea, C., Pardo, A. C., Rao, M. S., Rothstein, J. D., & Maragakis, N. J. (2008) · Nature Neuroscience · doi:10.1038/nn.2210 · Cited by 441
Astrocytes in human central nervous system diseases: a frontier for new therapies
Verkhratsky, A., Butt, A., Li, B., Illes, P., Zorec, R., Semyanov, A., Tang, Y., & Sofroniew, M. V. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01628-9 · Cited by 428
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 448
The Nrf2/ARE Pathway as a Potential Therapeutic Target in Neurodegenerative Disease
Calkins, M. J., Johnson, D. A., Townsend, J. A., Vargas, M. R., Dowell, J. A., Williamson, T. P., Kraft, A. D., Lee, J., Li, J., & Johnson, J. A. (2008) · Antioxidants and Redox Signaling · doi:10.1089/ars.2008.2242 · Cited by 441
Transient Opening of the Mitochondrial Permeability Transition Pore Induces Microdomain Calcium Transients in Astrocyte Processes
Agarwal, A., Wu, P.-H., Hughes, E. G., Fukaya, M., Tischfield, M. A., Langseth, A. J., Wirtz, D., & Bergles, D. E. (2017) · Neuron · doi:10.1016/j.neuron.2016.12.034 · Cited by 441
Astrocyte 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
Astrocytes in Neurodegenerative Disease: Table 1.
Phatnani, H., & Maniatis, T. (2015) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a020628 · Cited by 420
Neuronal Exosomal miRNA-dependent Translational Regulation of Astroglial Glutamate Transporter GLT1
Morel, L., Regan, M., Higashimori, H., Ng, S. K., Esau, C., Vidensky, S., Rothstein, J., & Yang, Y. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.410944 · Cited by 430
Necroptosis Drives Motor Neuron Death in Models of Both Sporadic and Familial ALS
Ré, D. B., Verche, V. L., Yu, C., Amoroso, M. W., Politi, K. A., Phani, S., Ikiz, B., Hoffmann, L., Koolen, M., Nagata, T., et al. (2014) · Neuron · doi:10.1016/j.neuron.2014.01.011 · Cited by 421
Self-citation
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Kim, K., Lee, S., Kegelman, T. P., Su, Z.-Z., Das, S. K., Dash, R., Dasgupta, S., Barral, P. M., Hedvat, M., Diaz, P. W., et al. (2010) · Journal of Cellular Physiology · doi:10.1002/jcp.22609 · Cited by 396
The genetics and neuropathology of amyotrophic lateral sclerosis
Al‐Chalabi, A., Jones, A., Troakes, C., King, A., Al‐Sarraj, S., & van den Berg, L. H. (2012) · Acta Neuropathologica · doi:10.1007/s00401-012-1022-4 · Cited by 419
The Seeds of Neurodegeneration: Prion-like Spreading in ALS
Polymenidou, M., & Cleveland, D. W. (2011) · Cell · doi:10.1016/j.cell.2011.10.011 · Cited by 382
Reactive 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
T lymphocytes potentiate endogenous neuroprotective inflammation in a mouse model of ALS
Chiu, I. M., Chen, A., Zheng, Y., Kosaras, B., Tsiftsoglou, S. A., Vartanian, T. K., Brown, R. H., & Carroll, M. C. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0804610105 · Cited by 380
Role of Neuroinflammation in Amyotrophic Lateral Sclerosis: Cellular Mechanisms and Therapeutic Implications
Liu, J., & Wang, F. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01005 · Cited by 376
Targeting mi R‐155 restores abnormal microglia and attenuates disease in SOD 1 mice
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
Expression of mutant huntingtin in mouse brain astrocytes causes age-dependent neurological symptoms
Bradford, J. W., Shin, J., Redd, M. A., Wang, C.-E., Li, X.-J., & Li, S. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0911503106 · Cited by 362
Postmortem Cortex Samples Identify Distinct Molecular Subtypes of ALS: Retrotransposon Activation, Oxidative Stress, and Activated Glia
Tam, O. H., Rozhkov, N. V., Shaw, R., Kim, D., Hubbard, I., Fennessey, S., Propp, N., Phatnani, H., Kwan, J., Sareen, D., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.09.066 · Cited by 327
Motor neuron vulnerability and resistance in amyotrophic lateral sclerosis
Nijssen, J., Comley, L. H., & Hedlund, E. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1708-8 · Cited by 353
Trehalose delays the progression of amyotrophic lateral sclerosis by enhancing autophagy in motoneurons
Castillo, K., Nassif, M., Valenzuela, V., Rojas, F., Matus, S., Mercado, G., Court, F. A., van Zundert, B., & Hetz, C. A. (2013) · Autophagy · doi:10.4161/auto.25188 · Cited by 345
Abnormal mitochondrial transport and morphology are common pathological denominators in SOD1 and TDP43 ALS mouse models
Magrané, J., Cortez, C. A., Gan, W., & Manfredi, G. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt528 · Cited by 359
Review: The role of vitamin D in nervous system health and disease
DeLuca, G. C., Kimball, S., Kolasinski, J., Ramagopalan, S. V., & Ebers, G. C. (2013) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12020 · Cited by 340
Clinical perspective on oxidative stress in sporadic amyotrophic lateral sclerosis
D’Amico, E., Factor-Litvak, P. R., Santella, R. M., & Mitsumoto, H. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.06.029 · Cited by 328
Emerging mechanisms of molecular pathology in ALS
Peters, O. M., Ghasemi, M., & Brown, R. H. (2015) · Journal of Clinical Investigation · doi:10.1172/jci71601 · Cited by 328
Skeletal muscle-restricted expression of human SOD1 causes motor neuron degeneration in transgenic mice
Wong, M., & Martin, L. J. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq106 · Cited by 318
Astrocyte-encoded positional cues maintain sensorimotor circuit integrity
Molofsky, A. V., Kelley, K. W., Tsai, H., Redmond, S., Chang, S., Madireddy, L., Chan, J. R., Baranzini, S. E., Ullian, E. M., & Rowitch, D. H. (2014) · Nature · doi:10.1038/nature13161 · Cited by 322
Mutant SOD1 in cell types other than motor neurons and oligodendrocytes accelerates onset of disease in ALS mice
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
Fingolimod: Direct CNS effects of sphingosine 1-phosphate (S1P) receptor modulation and implications in multiple sclerosis therapy
Groves, A., Kihara, Y., & Chun, J. J. M. (2013) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2013.02.011 · Cited by 318
Mitochondrial Dysfunction in SOD1G93A-Bearing Astrocytes Promotes Motor Neuron Degeneration: Prevention by Mitochondrial-Targeted Antioxidants
Cassina, P., Cassina, A., Pehar, M., Castellanos, R., Gandelman, M., de León, A., Robinson, K. M., Mason, R. P., Beckman, J. S., Barbeito, L., et al. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.5308-07.2008 · Cited by 324
GDNF Secreting Human Neural Progenitor Cells Protect Dying Motor Neurons, but Not Their Projection to Muscle, in a Rat Model of Familial ALS
Suzuki, M., McHugh, J., Tork, C. A., Shelley, B., Klein, S. M., Aebischer, P., & Svendsen, C. N. (2007) · PLoS ONE · doi:10.1371/journal.pone.0000689 · Cited by 311
RETRACTED: Neuroinflammatory Markers: Key Indicators in the Pathology of Neurodegenerative Diseases
Rauf, A., Badoni, H., Abu‐Izneid, T., Olatunde, A., Rahman, M. M., Painuli, S., Semwal, P., Wilairatana, P., & Mubarak, M. S. (2022) · Molecules · doi:10.3390/molecules27103194 · Cited by 316
Retracted
Adenosine signaling and function in glial cells
Boison, D., Chen, J., & Fredholm, B. B. (2009) · Cell Death and Differentiation · doi:10.1038/cdd.2009.131 · Cited by 319
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Yang, Y. M., Gupta, S. K., Kim, K. J., Powers, B. E., Cerqueira, A., Wainger, B. J., Ngo, H. D., Rosowski, K. A., Schein, P. A., Ackeifi, C. A., et al. (2013) · Cell stem cell · doi:10.1016/j.stem.2013.04.003 · Cited by 312
Neuroglia in neurodegeneration
Heneka, M. T., Rodriguez, J. J., & Verkhratsky, A. (2009) · Brain Research Reviews · doi:10.1016/j.brainresrev.2009.11.004 · Cited by 316
Progress toward the clinical application of patient-specific pluripotent stem cells
Kiskinis, E., & Eggan, K. (2010) · Journal of Clinical Investigation · doi:10.1172/jci40553 · Cited by 339
The Nrf2–ARE cytoprotective pathway in astrocytes
Vargas, M. R., & Johnson, J. A. (2009) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399409001094 · Cited by 295
Astrocytes: Implications for Neuroinflammatory Pathogenesis of Alzheimers Disease
Li, C., Zhao, R., Gao, K., Wei, Z. Z., Yin, M. Y., Lau, L. T., Chui, D., & Yu, A. C. (2011) · Current Alzheimer Research · doi:10.2174/156720511794604543 · Cited by 294
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
Astrocyte-derived extracellular vesicles: Neuroreparative properties and role in the pathogenesis of neurodegenerative disorders
Upadhya, R., Zingg, W., Shetty, S., & Shetty, A. K. (2020) · Journal of Controlled Release · doi:10.1016/j.jconrel.2020.04.017 · Cited by 282
Knockout of reactive astrocyte activating factors slows disease progression in an ALS mouse model
Guttenplan, K. A., Weigel, M. K., Adler, D. I., Couthouis, J., Liddelow, S. A., Gitler, A. D., & Barres, B. A. (2020) · Nature Communications · doi:10.1038/s41467-020-17514-9 · Cited by 278
Mutant Copper-Zinc Superoxide Dismutase (SOD1) Induces Protein Secretion Pathway Alterations and Exosome Release in Astrocytes
Basso, M., Pozzi, S., Tortarolo, M., Fiordaliso, F., Bisighini, C., Pasetto, L., Spaltro, G., Lidonnici, D., Gensano, F., Battaglia, E., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.425066 · Cited by 295
Protective and Toxic Neuroinflammation in Amyotrophic Lateral Sclerosis
Hooten, K. G., Beers, D. R., Zhao, W., & Appel, S. H. (2015) · Neurotherapeutics · doi:10.1007/s13311-014-0329-3 · Cited by 294
Loss of astrocytic domain organization in the epileptic brain
Oberheim, N. A., Tian, G.-F., Han, X., Peng, W., Takano, T., Ransom, B., & Nedergaard, M. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.4980-07.2008 · Cited by 303
Microglial Activation Correlates with Disease Progression and Upper Motor Neuron Clinical Symptoms in Amyotrophic Lateral Sclerosis
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
The Stem Cell Niche in Regenerative Medicine
Wagers, A. J. (2012) · Cell stem cell · doi:10.1016/j.stem.2012.02.018 · Cited by 281
Nitric Oxide in Health and Disease of the Nervous System
Knott, A. B., & Bossy‐Wetzel, E. (2008) · Antioxidants and Redox Signaling · doi:10.1089/ars.2008.2234 · Cited by 275
Pathological hallmarks of amyotrophic lateral sclerosis/frontotemporal lobar degeneration in transgenic mice produced with TDP-43 genomic fragments
Swarup, V., Phaneuf, D., Bareil, C., Robertson, J., Rouleau, G. A., Križ, J., & Julien, J. (2011) · Brain · doi:10.1093/brain/awr159 · Cited by 270
Questions and (some) answers on reactive astrocytes
Escartin, C., Guillemaud, O., & Carrillo‐de Sauvage, M. (2019) · Glia · doi:10.1002/glia.23687 · Cited by 275

Authors: Nagai, M., Re, D. B., Nagata, T., Chalazonitis, A., Jessell, T. M., Wichterle, H., & Przedborski, S.
Affiliations: Columbia University (US)
Howard Hughes Medical Institute (US)
Corresponding author: Przedborski, Serge
ORCID: Nagai, Makiko
Nagata, Tetsuya
Chalazonitis, Alcmène
Wichterle, Hynek
Przedborski, Serge
Venue: Nature Neuroscience
Publisher: Springer Science and Business Media LLC
Published: 2007-04-15
Volume: 10
Issue: 5
Pages: 615-622
ISSN: 1097-6256 (ISSN-L)
1546-1726
DOI: 10.1038/nn1876
PMC: PMC3799799
OpenAlex: W2107660300
Cited by: 1,220
References: 39
Citations by year: 2026: 22 · 2025: 31 · 2024: 59 · 2023: 52 · 2022: 50 · 2021: 52 · 2020: 65 · 2019: 53 · 2018: 58 · 2017: 72 · 2016: 53 · 2015: 64 · 2014: 81 · 2013: 84 · 2012: 89
FWCI: 57.88
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature Neuroscience (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: Muscular Dystrophy Association
National Institutes of Health
National Institute on Aging (R01AG021617, AG21617)
National Institute of Diabetes and Digestive and Kidney Diseases (DK58056, R01DK058056)
National Institute of Neurological Disorders and Stroke (NS-11766, P01NS011766, R01NS042269, P50NS038370, NS 42269, NS38370)
National Institute of Environmental Health Sciences (R21ES013177, ES013177)
Topics: Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
Keywords: amyotrophic lateral sclerosis, SOD1 mutations, astrocytes, motor neuron degeneration, non-cell autonomous neurodegeneration, spinal motoneurons
MeSH terms: Amyotrophic Lateral Sclerosis, Animals, Astrocytes, Cell Survival, Cells, Cultured, Disease Models, Animal, Dose-Response Relationship, Drug, Embryo, Mammalian, Enzyme Inhibitors, Ganglia, Spinal, Humans, Mice, Transgenic, Motor Neurons, Mutation, Nerve Tissue Proteins, Superoxide Dismutase, Culture Media, Conditioned, In Situ Nick-End Labeling, Green Fluorescent Proteins, Mice, Embryonic Stem Cells

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Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons

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