R. Albano, X. Liu, and D. Lobner, Regulation of system x(c)-in the SOD1-G93A mouse model of ALS, Exp Neurol, vol.250, pp.69-73, 2013.

J. W. Allen, G. Shanker, K. H. Tan, and M. Aschner, The consequences of methylmercury exposure on interactive functions between astrocytes and neurons, Neurotoxicology, vol.23, pp.755-764, 2002.

D. R. Beers, J. S. Henkel, Q. Xiao, W. Zhao, J. Wang et al., Wildtype microglia extend survival in PU.1 knockout mice with familial amyotrophic lateral sclerosis, Proc Natl Acad Sci, vol.103, pp.16021-16027, 2006.

D. R. Beers, J. S. Henkel, W. Zhao, J. Wang, A. Huang et al., Endogenous regulatory T lymphocytes ameliorate amyotrophic lateral sclerosis in mice and correlate with disease progression in patients with amyotrophic lateral sclerosis, Brain, vol.134, pp.1293-314, 2011.

G. Bensimon, L. Lacomblez, and V. Meininger, A controlled trial of riluzole in amyotrophic lateral sclerosis. ALS/Riluzole Study Group, N Engl J Med, vol.330, pp.585-91, 1994.

H. O. Beutler, Methods of enzymatic analysis, pp.369-76, 1985.

S. Boillee, V. Velde, C. Cleveland, and D. W. , ALS: a disease of motor neurons and their nonneuronal neighbors, Neuron, vol.52, pp.39-59, 2006.

S. Boillee, K. Yamanaka, C. S. Lobsiger, N. G. Copeland, N. A. Jenkins et al., Onset and progression in inherited ALS determined by motor neurons and microglia, Science, vol.312, pp.1389-92, 2006.

J. Burdo, R. Dargusch, and D. Schubert, Distribution of the cystine/glutamate antiporter system xc-in the brain, kidney, and duodenum, J Histochem Cytochem, vol.54, pp.549-57, 2006.

I. M. Chiu, E. T. Morimoto, H. Goodarzi, J. T. Liao, S. O'keeffe et al., A neurodegeneration-specific gene-expression signature of acutely isolated microglia from an amyotrophic lateral sclerosis mouse model, Cell Rep, vol.4, pp.385-401, 2013.

S. H. Choi, S. Aid, H. W. Kim, S. H. Jackson, and F. Bosetti, Inhibition of NADPH oxidase promotes alternative and anti-inflammatory microglial activation during neuroinflammation, J Neurochem, vol.120, pp.292-301, 2012.

W. J. Chung, S. A. Lyons, G. M. Nelson, H. Hamza, C. L. Gladson et al., Inhibition of cystine uptake disrupts the growth of primary brain tumors, J Neurosci, vol.25, pp.7101-7111, 2005.

A. M. Clement, M. D. Nguyen, E. A. Roberts, M. L. Garcia, S. Boillee et al., Wild-type nonneuronal cells extend survival of SOD1 mutant motor neurons in ALS mice, Science, vol.302, pp.113-120, 2003.

P. Corcia, C. Tauber, J. Vercoullie, N. Arlicot, C. Prunier et al., Molecular imaging of microglial activation in amyotrophic lateral sclerosis, PLoS One, vol.7, p.52941, 2012.

M. Czeh, P. Gressens, and A. M. Kaindl, The yin and yang of microglia, Dev Neurosci, vol.33, pp.199-209, 2011.

D. Bundel, D. Schallier, A. Loyens, E. Fernando, R. Miyashita et al., Loss of system x(c)-does not induce oxidative stress but decreases extracellular glutamate in hippocampus and influences spatial working memory and limbic seizure susceptibility, J Neurosci, vol.31, pp.5792-803, 2011.

C. J. De-groot, L. Montagne, I. Janssen, R. Ravid, P. Van-der-valk et al., Isolation and characterization of adult microglial cells and oligodendrocytes derived from postmortem human brain tissue, Brain Res Brain Res Protoc, vol.5, pp.85-94, 2000.

M. Domercq, M. V. Sanchez-gomez, C. Sherwin, E. Etxebarria, R. Fern et al., System xc-and glutamate transporter inhibition mediates microglial toxicity to oligodendrocytes, J Immunol, vol.178, pp.6549-56, 2007.

C. J. Donnelly, P. W. Zhang, J. T. Pham, A. R. Haeusler, N. A. Mistry et al., RNA toxicity from the ALS/FTD C9ORF72 expansion is mitigated by antisense intervention, Neuron, vol.80, pp.415-443, 2013.

R. Dringen and J. Hirrlinger, Glutathione pathways in the brain, Biol Chem, vol.384, pp.505-521, 2003.

E. Foran and D. Trotti, Glutamate transporters and the excitotoxic path to motor neuron degeneration in amyotrophic lateral sclerosis, Antioxid Redox Signal, vol.11, pp.1587-602, 2009.

E. Gasol, M. Jimenez-vidal, J. Chillaron, A. Zorzano, and M. Palacin, Membrane topology of system xc-light subunit reveals a re-entrant loop with substrate-restricted accessibility, J Biol Chem, vol.279, pp.31228-31264, 2004.

G. E. Gochenauer and M. B. Robinson, Dibutyryl-cAMP (dbcAMP) up-regulates astrocytic chloride-dependent L-[3H]glutamate transport and expression of both system xc(-) subunits, J Neuroch, vol.78, pp.276-86, 2001.

J. S. Henkel, J. I. Engelhardt, L. Siklos, E. P. Simpson, S. H. Kim et al., Presence of dendritic cells, MCP-1, and activated microglia/macrophages in amyotrophic lateral sclerosis spinal cord tissue, Ann Neurol, vol.55, pp.221-256, 2004.

T. Hideyama, T. Yamashita, H. Aizawa, S. Tsuji, A. Kakita et al., Profound downregulation of the RNA editing enzyme ADAR2 in ALS spinal motor neurons, Neurobiol Dis, vol.45, pp.1121-1129, 2012.

D. S. Howland, J. Liu, Y. She, B. Goad, N. J. Maragakis et al., Focal loss of the glutamate transporter EAAT2 in a transgenic rat model of SOD1 mutant-mediated amyotrophic lateral sclerosis (ALS), Proc Natl Acad Sci, vol.99, pp.1604-1613, 2002.

A. M. Kaindl, V. Degos, S. Peineau, E. Gouadon, V. Chhor et al., Activation of microglial N-methyl-D-aspartate receptors triggers inflammation and neuronal cell death in the developing and mature brain, Ann Neurol, vol.72, pp.536-585, 2012.

S. H. Kang, Y. Li, M. Fukaya, I. Lorenzini, D. W. Cleveland et al., Degeneration and impaired regeneration of gray matter oligodendrocytes in amyotrophic lateral sclerosis, Nat Neurosci, vol.16, pp.571-580, 2013.

Y. Kawahara, K. Ito, H. Sun, H. Aizawa, I. Kanazawa et al., Glutamate receptors: RNA editing and death of motor neurons, Nature, vol.427, p.801, 2004.

K. Kobayashi, S. Imagama, T. Ohgomori, K. Hirano, K. Uchimura et al., Minocycline selectively inhibits M1 polarization of microglia, Cell Death Dis, vol.4, p.525, 2013.

D. Lambrechts, E. Storkebaum, M. Morimoto, J. Del-favero, F. Desmet et al., VEGF is a modifier of amyotrophic lateral sclerosis in mice and humans and protects motoneurons against ischemic death, Nat Genet, vol.34, pp.383-94, 2003.

B. J. Lerman, E. P. Hoffman, M. L. Sutherland, K. Bouri, D. K. Hsu et al., Deletion of galectin-3 exacerbates microglial activation and accelerates disease progression and demise in a SOD1(G93A) mouse model of amyotrophic lateral sclerosis, Brain Behav, vol.2, pp.563-75, 2012.

J. Lewerenz, P. Albrecht, M. L. Tien, N. Henke, S. Karumbayaram et al., Induction of Nrf2 and xCT are involved in the action of the neuroprotective antibiotic ceftriaxone in vitro, J Neuroch, vol.111, pp.332-375, 2009.

J. Lewerenz, S. J. Hewett, Y. Huang, M. Lambros, P. W. Gout et al., The cystine/glutamate antiporter system x(c)(-) in health and disease: from molecular mechanisms to novel therapeutic opportunities, Antioxid Redox Signal, vol.18, pp.522-55, 2013.

B. Liao, W. Zhao, D. R. Beers, J. S. Henkel, and S. H. Appel, Transformation from a neuroprotective to a neurotoxic microglial phenotype in a mouse model of ALS, Exp Neurol, vol.237, pp.147-52, 2012.

C. S. Lobsiger, S. Boillee, and D. W. Cleveland, Toxicity from different SOD1 mutants dysregulates the complement system and the neuronal regenerative response in ALS motor neurons, Proc Natl Acad Sci, vol.104, pp.7319-7345, 2007.

C. S. Lobsiger, S. Boillee, M. Mcalonis-downes, A. M. Khan, M. L. Feltri et al., Schwann cells expressing dismutase active mutant SOD1 unexpectedly slow disease progression in ALS mice, Proc Natl Acad Sci, vol.106, pp.4465-70, 2009.

I. Maezawa and L. W. Jin, Rett syndrome microglia damage dendrites and synapses by the elevated release of glutamate, J Neurosci, vol.30, pp.5346-56, 2010.

J. J. Marden, M. M. Harraz, A. J. Williams, K. Nelson, M. Luo et al., Redox modifier genes in amyotrophic lateral sclerosis in mice, J Clin Invest, vol.117, pp.2913-2922, 2007.

A. J. Markowitz, M. G. White, D. L. Kolson, and J. Kl, Cellular interplay between neurons and glia: toward a comprehensive mechanism for excitotoxic neuronal loss in neurodegeneration, Cellscience, vol.4, pp.111-157, 2007.

A. Massie, A. Schallier, S. W. Kim, R. Fernando, S. Kobayashi et al., Dopaminergic neurons of system x(c)(-)-deficient mice are highly protected against 6-hydroxydopamine-induced toxicity, FASEB J, vol.25, pp.1359-69, 2011.

A. Massie, A. Schallier, B. Mertens, K. Vermoesen, S. Bannai et al., Time-dependent changes in striatal xCT protein expression in hemi-Parkinson rats, Neuroreport, vol.19, pp.1589-92, 2008.

M. Milanese, S. Zappettini, F. Onofri, L. Musazzi, D. Tardito et al., Abnormal exocytotic release of glutamate in a mouse model of amyotrophic lateral sclerosis, J Neurochem, vol.116, pp.1028-1070, 2011.

T. A. Ogunrinu and H. Sontheimer, Hypoxia increases the dependence of glioma cells on glutathione, J Biol Chem, vol.285, pp.37716-37740, 2010.

D. Piani and A. Fontana, Involvement of the cystine transport system xc-in the macrophage-induced glutamate-dependent cytotoxicity to neurons, J Immunol, vol.152, pp.3578-85, 1994.

C. Pitzer, C. Kruger, C. Plaas, F. Kirsch, T. Dittgen et al., Granulocyte-colony stimulating factor improves outcome in a mouse model of amyotrophic lateral sclerosis, Brain, vol.131, pp.3335-3382, 2008.

D. V. Pow, Visualising the activity of the cystine-glutamate antiporter in glial cells using antibodies to aminoadipic acid, a selectively transported substrate, Glia, vol.34, pp.27-38, 2001.

S. Qin, C. Colin, I. Hinners, A. Gervais, C. Cheret et al., System Xcand apolipoprotein E expressed by microglia have opposite effects on the neurotoxicity of amyloid-beta peptide 1-40, J Neurosci, vol.26, pp.3345-56, 2006.

D. R. Rosen, T. Siddique, D. Patterson, D. A. Figlewicz, P. Sapp et al., Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis, Nature, vol.362, pp.59-62, 1993.

J. D. Rothstein, M. Van-kammen, A. I. Levey, L. J. Martin, and R. W. Kuncl, Selective loss of glial glutamate transporter GLT-1 in amyotrophic lateral sclerosis, Ann Neurol, vol.38, pp.73-84, 1995.

J. I. Sagara, K. Miura, and S. Bannai, Maintenance of neuronal glutathione by glial cells, J Neurochem, vol.61, pp.1672-1678, 1993.

H. Sato, K. Kuriyama-matsumura, T. Hashimoto, H. Sasaki, H. Wang et al., Effect of oxygen on induction of the cystine transporter by bacterial lipopolysaccharide in mouse peritoneal macrophages, J Biol Chem, vol.276, pp.10407-10419, 2001.

H. Sato, A. Shiiya, M. Kimata, K. Maebara, M. Tamba et al., Redox imbalance in cystine/glutamate transporter-deficient mice, J Biol Chem, vol.280, pp.37423-37432, 2005.

H. Sato, M. Tamba, T. Ishii, and S. Bannai, Cloning and expression of a plasma membrane cystine/glutamate exchange transporter composed of two distinct proteins, J Biol Chem, vol.274, pp.11455-11463, 1999.

H. Sato, M. Tamba, S. Okuno, K. Sato, K. Keino-masu et al., Distribution of cystine/glutamate exchange transporter, system x(c)-, in the mouse brain, J Neurosci, vol.22, pp.8028-8061, 2002.

A. Schneider, C. Kruger, T. Steigleder, D. Weber, C. Pitzer et al., The hematopoietic factor G-CSF is a neuronal ligand that counteracts programmed cell death and drives neurogenesis, J Clin Invest, vol.115, pp.2083-98, 2005.

H. Takeuchi, J. S. Wang, J. Zhang, G. Kawanokuchi, J. Kuno et al., Tumor necrosis factor-alpha induces neurotoxicity via glutamate release from hemichannels of activated microglia in an autocrine manner, J Biol Chem, vol.281, pp.21362-21370, 2006.

H. Takeuchi, H. Mizoguchi, Y. Doi, J. S. Noda, M. Liang et al., Blockade of gap junction hemichannel suppresses disease progression in mouse models of amyotrophic lateral sclerosis and Alzheimer's disease, PLoS One, vol.6, p.21108, 2011.

H. Takuma, S. Kwak, T. Yoshizawa, and I. Kanazawa, Reduction of GluR2 RNA editing, a molecular change that increases calcium influx through AMPA receptors, selective in the spinal ventral gray of patients with amyotrophic lateral sclerosis, Ann Neurol, vol.46, pp.806-821, 1999.

C. Thery, B. Chamak, and M. Mallat, Cytotoxic effect of brain macrophages on developing, Eur J Neurosci, vol.3, pp.1155-64, 1991.

M. R. Turner, A. Cagnin, F. E. Turkheimer, C. C. Miller, C. E. Shaw et al., Evidence of widespread cerebral microglial activation in amyotrophic lateral sclerosis: an [11C](R)-PK11195 positron emission tomography study, Neurobiol Dis, vol.15, pp.601-610, 2004.

I. Vaknin, G. Kunis, O. Miller, O. Butovsky, S. Bukshpan et al., Excess circulating alternatively activated myeloid (M2) cells accelerate ALS progression while inhibiting experimental autoimmune encephalomyelitis, PLoS One, vol.6, p.26921, 2011.

P. Van-damme, D. Braeken, G. Callewaert, W. Robberecht, . Van-den et al., GluR2 deficiency accelerates motor neuron degeneration in a mouse model of amyotrophic lateral sclerosis, J Neuropathol Exp Neurol, vol.64, pp.605-617, 2005.

L. Van-den-bosch, P. Van-damme, E. Bogaert, and W. Robberecht, The role of excitotoxicity in the pathogenesis of amyotrophic lateral sclerosis, Biochim Biophys Acta, vol.1762, pp.1068-82, 2006.

L. Wang, H. X. Deng, G. Grisotti, H. Zhai, T. Siddique et al., Wildtype SOD1 overexpression accelerates disease onset of a G85R SOD1 mouse, Hum Mol Genet, vol.18, pp.1642-51, 2009.

H. Watanabe and S. Bannai, Induction of cystine transport activity in mouse peritoneal macrophages, J Exp Med, vol.165, pp.628-668, 1987.

D. C. Wu, D. B. Re, M. Nagai, H. Ischiropoulos, and S. Przedborski, The inflammatory NADPH oxidase enzyme modulates motor neuron degeneration in amyotrophic lateral sclerosis mice, Proc Natl Acad Sci, vol.103, pp.12132-12139, 2006.

J. Xue, S. V. Schmidt, J. Sander, A. Draffehn, W. Krebs et al., Transcriptome-based network analysis reveals a spectrum model of human macrophage activation, Immunity, vol.40, pp.274-88, 2014.

K. Yamanaka, S. J. Chun, S. Boillee, N. Fujimori-tonou, H. Yamashita et al., Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis, Nat Neurosci, vol.11, pp.251-254, 2008.

X. Zhang, L. Li, S. Chen, D. Yang, Y. Wang et al., Rapamycin treatment augments motor neuron degeneration in SOD1(G93A) mouse model of amyotrophic lateral sclerosis, Autophagy, vol.7, pp.412-437, 2011.

S. Zhu, I. G. Stavrovskaya, M. Drozda, B. Y. Kim, V. Ona et al., Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice, Nature, vol.417, pp.74-82, 2002.