Neuroimmunity dynamics and the development of therapeutic strategies for amyotrophic lateral sclerosis

Frontiers in Cellular Neuroscience

Volumn 7, Issue NOV, 2013, Pages

  Bowerman, Melissa ^a   Vincent, Thierry ^a   Scamps, Frédérique ^a   Perrin, Florence E ^a,b   Camu, William ^a,c   Raoul, Cédric ^a  

^a HÔPITAL SAINT ELOI   (France)

^b UNIV MONTPELLIER   (France)

^c GUI DE CHAULIAC HOSPITAL   (France)

Author keywords

Astrocytes; Cytokine; Hyperexcitability; Inflammation; Lymphocytes; Microglia; Therapy

Indexed keywords

CD14 ANTIGEN; CYCLOOXYGENASE 2; GALECTIN 3; GAMMA INTERFERON; GLIAL CELL LINE DERIVED NEUROTROPHIC FACTOR; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INDUCIBLE NITRIC OXIDE SYNTHASE; INTERLEUKIN 10; INTERLEUKIN 12; INTERLEUKIN 15; INTERLEUKIN 17; INTERLEUKIN 1BETA; INTERLEUKIN 23; INTERLEUKIN 4; INTERLEUKIN 6; KI 67 ANTIGEN; LYMPHOTOXIN BETA RECEPTOR; MINOCYCLINE; MONOCYTE CHEMOTACTIC PROTEIN 1; OPTINEURIN; PLACEBO; PURINERGIC P2X RECEPTOR; PURINERGIC P2X4 RECEPTOR; PURINERGIC P2X7 RECEPTOR; PURINERGIC P2Y RECEPTOR; THALIDOMIDE; TOLL LIKE RECEPTOR 2; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR ALPHA; UNINDEXED DRUG;

ALZHEIMER DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; ARTICLE; CELL PROLIFERATION; DISEASE ASSOCIATION; DISEASE COURSE; EXCITOTOXICITY; HUMAN; IMMUNITY; MICROGLIA; NERVE INJURY; NERVOUS SYSTEM INFLAMMATION; NEUROIMMUNITY; NEUROPATHIC PAIN; NEUROPROTECTION; NEUROTOXICITY; NONHUMAN; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PROTEIN EXPRESSION; RANDOMIZED CONTROLLED TRIAL (TOPIC); SIGNAL TRANSDUCTION; SPASTICITY; UNSPECIFIED SIDE EFFECT;

EID: 84888415764     PISSN: 16625102     EISSN: None     Source Type: Journal    
DOI: 10.3389/fncel.2013.00214     Document Type: Article

References (130)

1. Aebischer, J., Benard-Marissal, N., Pettmann, B., and Raoul, C. (2013). Death receptors in the selective degeneration of motoneurons in amyotrophic lateral sclerosis. J. Neurodegener. Dis. 2013, 746845. doi: 10.1155/2013/746845.
2. Aebischer, J., Cassina, P., Otsmane, B., Moumen, A., Seilhean, D., Meininger, V., et al. (2011). IFNgamma triggers a LIGHT-dependent selective death of motoneurons contributing to the non-cell-autonomous effects of mutant SOD1. Cell Death Differ. 18, 754-768. doi: 10.1038/cdd.2010.143.
3. Aebischer, J., Moumen, A., Sazdovitch, V., Seilhean, D., Meininger, V., and Raoul, C. (2012). Elevated levels of IFNgamma and LIGHT in the spinal cord of patients with sporadic amyotrophic lateral sclerosis. Eur. J. Neurol. 19, 752-759. doi: 10.1111/j.1468-1331.2011.03623.x.
4. Alexianu, M. E., Kozovska, M., and Appel, S. H. (2001). Immune reactivity in a mouse model of familial ALS correlates with disease progression. Neurology 57, 1282-1289. doi: 10.1212/WNL.57.7.1282.
5. Apolloni, S., Amadio, S., Montilli, C., Volonte, C., and D'Ambrosi, N. (2013). Ablation of P2X7 receptor exacerbates gliosis and motoneuron death in the SOD1-G93A mouse model of amyotrophic lateral sclerosis. Hum. Mol. Genet. 22, 4102-4116. doi: 10.1093/hmg/ddt259.
6. Appel, S. H., Engelhardt, J. I., Garcia, J., and Stefani, E. (1991). Immunoglobulins from animal models of motor neuron disease and from human amyotrophic lateral sclerosis patients passively transfer physiological abnormalities to the neuromuscular junction. Proc. Natl. Acad. Sci. U.S.A. 88, 647-651. doi: 10.1073/pnas.88.2.647.
7. Backstrom, E., Chambers, B. J., Kristensson, K., and Ljunggren, H. G. (2000). Direct NK cell-mediated lysis of syngenic dorsal root ganglia neurons in vitro. J. Immunol.165, 4895-4900.
8. Bae, J. S., Simon, N. G., Menon, P., Vucic, S., and Kiernan, M. C. (2013). The puzzling case of hyperexcitability in amyotrophic lateral sclerosis. J. Clin. Neurol. 9, 65-74. doi: 10.3988/jcn.2013.9.2.65.
9. Banati, R. B., Gehrmann, J., Kellner, M., and Holsboer, F. (1995). Antibodies against microglia/brain macrophages in the cerebrospinal fluid of a patient with acute amyotrophic lateral sclerosis and presenile dementia. Clin. Neuropathol. 14, 197-200.
10. Bataveljic, D., Stamenkovic, S., Bacic, G., and Andjus, P. R. (2011). Imaging cellular markers of neuroinflammation in the brain of the rat model of amyotrophic lateral sclerosis. Acta Physiol. Hung. 98, 27-31. doi: 10.1556/APhysiol.98.2011.1.4.
11. Beers, D. R., Henkel, J. S., Xiao, Q., Zhao, W., Wang, J., Yen, A. A., et al. (2006). Wild-type microglia extend survival in PU.1 knockout mice with familial amyotrophic lateral sclerosis. Proc. Natl. Acad. Sci. U.S.A. 103, 16021-16026. doi: 10.1073/pnas.0607423103.
12. Beers, D. R., Henkel, J. S., Zhao, W., Wang, J., and Appel, S. H. (2008). CD4+ T cells support glial neuroprotection, slow disease progression, and modify glial morphology in an animal model of inherited ALS. Proc. Natl. Acad. Sci. U.S.A. 105, 15558-15563. doi: 10.1073/pnas.0807419105.
13. Beers, D. R., Henkel, J. S., Zhao, W., Wang, J., Huang, A., Wen, S., et al. (2011a). Endogenous regulatory T lymphocytes ameliorate amyotrophic lateral sclerosis in mice and correlate with disease progression in patients with amyotrophic lateral sclerosis. Brain 134, 1293-1314. doi: 10.1093/brain/awr074.
14. Beers, D. R., Zhao, W., Liao, B., Kano, O., Wang, J., Huang, A., et al. (2011b). Neuroinflammation modulates distinct regional and temporal clinical responses in ALS mice. Brain Behav. Immun. 25, 1025-1035. doi: 10.1016/j.bbi.2010.12.008.
15. Bento-Abreu, A., Van Damme, P., Van Den Bosch, L., and Robberecht, W. (2010). The neurobiology of amyotrophic lateral sclerosis. Eur. J. Neurosci. 31, 2247-2265. doi: 10.1111/j.1460-9568.2010.07260.x.
16. Bernard-Marissal, N., Moumen, A., Sunyach, C., Pellegrino, C., Dudley, K., Henderson, C. E., et al. (2012). Reduced calreticulin levels link endoplasmic reticulum stress and Fas-triggered cell death in motoneurons vulnerable to ALS. J. Neurosci. 32, 4901-4912. doi: 10.1523/JNEUROSCI.5431-11.2012.
17. Berson, A., Barbash, S., Shaltiel, G., Goll, Y., Hanin, G., Greenberg, D. S., et al. (2012). Cholinergic-associated loss of hnRNP-A/B in Alzheimer's disease impairs cortical splicing and cognitive function in mice. EMBO Mol. Med. 4, 730-742. doi: 10.1002/emmm.201100995.
18. Blaesse, P., Airaksinen, M. S., Rivera, C., and Kaila, K. (2009). Cation-chloride cotransporters and neuronal function. Neuron 61, 820-838. doi: 10.1016/j.neuron.2009.03.003.
19. Boillee, S., Yamanaka, K., Lobsiger, C. S., Copeland, N. G., Jenkins, N. A., Kassiotis, G., et al. (2006). Onset and progression in inherited ALS determined by motor neurons and microglia. Science 312, 1389-1392. doi: 10.1126/science.1123511.
20. Boulenguez, P., Liabeuf, S., Bos, R., Bras, H., Jean-Xavier, C., Brocard, C., et al. (2010). Down-regulation of the potassium-chloride cotransporter KCC2 contributes to spasticity after spinal cord injury. Nat. Med. 16, 302-307. doi: 10.1038/nm.2107.
21. Bours, M. J., Dagnelie, P. C., Giuliani, A. L., Wesselius, A., and Di Virgilio, F. (2011). P2 receptors and extracellular ATP: a novel homeostatic pathway in inflammation. Front. Biosci. 3:1443-1456. doi: 10.2741/235.
22. Brown, R. H. Jr., Hauser, S. L., Harrington, H., and Weiner, H. L. (1986). Failure of immunosuppression with a ten-to 14-day course of high-dose intravenous cyclophosphamide to alter the progression of amyotrophic lateral sclerosis. Arch. Neurol. 43, 383-384. doi: 10.1001/archneur.1986.00520040063021.
23. Buratti, E., Brindisi, A., Giombi, M., Tisminetzky, S., Ayala, Y. M., and Baralle, F. E. (2005). TDP-43 binds heterogeneous nuclear ribonucleoprotein A/B through its C-terminal tail: an important region for the inhibition of cystic fibrosis transmembrane conductance regulator exon 9 splicing. J. Biol. Chem. 280, 37572-37584. doi: 10.1074/jbc.M505557200.
24. Calvo, A., Moglia, C., Balma, M., and Chio, A. (2010). Involvement of immune response in the pathogenesis of amyotrophic lateral sclerosis: a therapeutic opportunity? CNS Neurol. Disord. Drug Targets 9, 325-330. doi: 10.2174/187152710791292657.
25. Casas, C., Herrando-Grabulosa, M., Manzano, R., Mancuso, R., Osta, R., and Navarro, X. (2013). Early presymptomatic cholinergic dysfunction in a murine model of amyotrophic lateral sclerosis. Brain Behav. 3, 145-158. doi: 10.1002/brb3.104.
26. Casula, M., Iyer, A. M., Spliet, W. G., Anink, J. J., Steentjes, K., Sta, M., et al. (2011). Toll-like receptor signaling in amyotrophic lateral sclerosis spinal cord tissue. Neuroscience 179, 233-243. doi: 10.1016/j.neuroscience.2011.02.001.
27. Cella, M., Otero, K., and Colonna, M. (2010). Expansion of human NK-22 cells with IL-7, IL-2, and IL-1beta reveals intrinsic functional plasticity. Proc. Natl. Acad. Sci. U.S.A. 107, 10961-10966. doi: 10.1073/pnas.1005641107.
28. Chiu, I. M., Chen, A., Zheng, Y., Kosaras, B., Tsiftsoglou, S. A., Vartanian, T. K., et al. (2008). T lymphocytes potentiate endogenous neuroprotective inflammation in a mouse model of ALS. Proc. Natl. Acad. Sci. U.S.A. 105, 17913-17918. doi: 10.1073/pnas.0804610105.
29. Coull, J. A., Beggs, S., Boudreau, D., Boivin, D., Tsuda, M., Inoue, K., et al. (2005). BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature 438, 1017-1021. doi: 10.1038/nature04223.
30. Coull, J. A., Boudreau, D., Bachand, K., Prescott, S. A., Nault, F., Sik, A., et al. (2003). Trans-synaptic shift in anion gradient in spinal lamina I neurons as a mechanism of neuropathic pain. Nature 424, 938-942. doi: 10.1038/nature01868.
31. Cudkowicz, M. E., Shefner, J. M., Schoenfeld, D. A., Zhang, H., Andreasson, K. I., Rothstein, J. D., et al. (2006). Trial of celecoxib in amyotrophic lateral sclerosis. Ann. Neurol. 60, 22-31. doi: 10.1002/ana.20903.
32. D'Ambrosi, N., Finocchi, P., Apolloni, S., Cozzolino, M., Ferri, A., Padovano, V., et al. (2009). The proinflammatory action of microglial P2 receptors is enhanced in SOD1 models for amyotrophic lateral sclerosis. J. Immunol. 183, 4648-4656. doi: 10.4049/jimmunol.0901212.
33. Davalos, D., Grutzendler, J., Yang, G., Kim, J. V., Zuo, Y., Jung, S., et al. (2005). ATP mediates rapid microglial response to local brain injury in vivo. Nat. Neurosci. 8, 752-758. doi: 10.1038/nn1472.
34. Demestre, M., Pullen, A., Orrell, R. W., and Orth, M. (2005). ALS-IgG-induced selective motor neurone apoptosis in rat mixed primary spinal cord cultures. J. Neurochem. 94, 268-275. doi: 10.1111/j.1471-4159.2005.03184.x.
35. Dibaj, P., Steffens, H., Zschuntzsch, J., Nadrigny, F., Schomburg, E. D., Kirchhoff, F., et al. (2011). In vivo imaging reveals distinct inflammatory activity of CNS microglia versus PNS macrophages in a mouse model for ALS. PLoS ONE 6:e17910. doi: 10.1371/journal.pone.0017910.
36. Donnenfeld, H., Kascsak, R. J., and Bartfeld, H. (1984). Deposits of IgG and C3 in the spinal cord and motor cortex of ALS patients. J. Neuroimmunol. 6, 51-57. doi: 10.1016/0165-5728(84)90042-0.
37. Drachman, D. B., Chaudhry, V., Cornblath, D., Kuncl, R. W., Pestronk, A., Clawson, L., et al. (1994). Trial of immunosuppression in amyotrophic lateral sclerosis using total lymphoid irradiation. Ann. Neurol. 35, 142-150. doi: 10.1002/ana.410350205.
38. Drachman, D. B., Frank, K., Dykes-Hoberg, M., Teismann, P., Almer, G., Przedborski, S., et al. (2002). Cyclooxygenase 2 inhibition protects motor neurons and prolongs survival in a transgenic mouse model of ALS. Ann. Neurol. 52, 771-778. doi: 10.1002/ana.10374.
39. Dupuis, L., Dengler, R., Heneka, M. T., Meyer, T., Zierz, S., Kassubek, J., et al. (2012). A randomized, double blind, placebo-controlled trial of pioglitazone in combination with riluzole in amyotrophic lateral sclerosis. PLoS ONE 7:e37885. doi: 10.1371/journal.pone.0037885.
40. Engelhardt, J. I., and Appel, S. H. (1990). IgG reactivity in the spinal cord and motor cortex in amyotrophic lateral sclerosis. Arch. Neurol. 47, 1210-1216. doi: 10.1001/archneur.1990.00530110068019.
41. Engelhardt, J. I., Siklos, L., Komuves, L., Smith, R. G., and Appel, S. H. (1995). Antibodies to calcium channels from ALS patients passively transferred to mice selectively increase intracellular calcium and induce ultrastructural changes in motoneurons. Synapse 20, 185-199. doi: 10.1002/syn.890200302.
42. Engelhardt, J. I., Tajti, J., and Appel, S. H. (1993). Lymphocytic infiltrates in the spinal cord in amyotrophic lateral sclerosis. Arch. Neurol. 50, 30-36. doi: 10.1001/archneur.1993.00540010026013.
43. Fendrick, S. E., Xue, Q. S., and Streit, W. J. (2007). Formation of multinucleated giant cells and microglial degeneration in rats expressing a mutant Cu/Zn superoxide dismutase gene. J. Neuroinflammation 4, 9. doi: 10.1186/1742-2094-4-9.
44. Fiala, M., Chattopadhay, M., La Cava, A., Tse, E., Liu, G., Lourenco, E., et al. (2010). IL-17A is increased in the serum and in spinal cord CD8 and mast cells of ALS patients.J. Neuroinflammation 7, 76. doi: 10.1186/1742-2094-7-76.
45. Finkelstein, A., Kunis, G., Seksenyan, A., Ronen, A., Berkutzki, T., Azoulay, D., et al. (2011). Abnormal changes in NKT cells, the IGF-1 axis, and liver pathology in an animal model of ALS. PLoS ONE 6:e22374. doi: 10.1371/journal.pone.0022374.
46. Fuchs, A., Ringer, C., Bilkei-Gorzo, A., Weihe, E., Roeper, J., and Schutz, B. (2010). Downregulation of the potassium chloride cotransporter KCC2 in vulnerable motoneurons in the SOD1-G93A mouse model of amyotrophic lateral sclerosis. J. Neuropathol. Exp. Neurol. 69, 1057-1070. doi: 10.1097/NEN.0b013e3181f4dcef.
47. Gandelman, M., Peluffo, H., Beckman, J. S., Cassina, P., and Barbeito, L. (2010). Extracellular ATP and the P2X7 receptor in astrocyte-mediated motor neuron death: implications for amyotrophic lateral sclerosis. J. Neuroinflammation 7, 33. doi: 10.1186/1742-2094-7-33.
48. Gerber, Y. N., Sabourin, J. C., Rabano, M., Vivanco, M., and Perrin, F. E. (2012). Early functional deficit and microglial disturbances in a mouse model of amyotrophic lateral sclerosis. PLoS ONE 7:e36000. doi: 10.1371/journal.pone.0036000.
49. Glass, C. K., Saijo, K., Winner, B., Marchetto, M. C., and Gage, F. H. (2010). Mechanisms underlying inflammation in neurodegeneration. Cell 140, 918-934. doi: 10.1016/j.cell.2010.02.016.
50. Gordon, P. H., Moore, D. H., Miller, R. G., Florence, J. M., Verheijde, J. L., Doorish, C., et al. (2007). Efficacy of minocycline in patients with amyotrophic lateral sclerosis: a phase III randomised trial. Lancet Neurol. 6, 1045-1053. doi: 10.1016/S1474-4422(07)70270-3.
51. Gourie-Devi, M., Nalini, A., and Subbakrishna, D. K. (1997). Temporary amelioration of symptoms with intravenous cyclophosphamide in amyotrophic lateral sclerosis. J. Neurol. Sci. 150, 167-172. doi: 10.1016/S0022-510X(97)00083-X.
52. Gowing, G., Philips, T., Van Wijmeersch, B., Audet, J. N., Dewil, M., Van Den Bosch, L., et al. (2008). Ablation of proliferating microglia does not affect motor neuron degeneration in amyotrophic lateral sclerosis caused by mutant superoxide dismutase. J. Neurosci. 28, 10234-10244. doi: 10.1523/JNEUROSCI.3494-08.2008.
53. Graber, D. J., Hickey, W. F., and Harris, B. T. (2010). Progressive changes in microglia and macrophages in spinal cord and peripheral nerve in the transgenic rat model of amyotrophic lateral sclerosis. J. Neuroinflammation 7, 8. doi: 10.1186/1742-2094-7-8.
54. Graves, M. C., Fiala, M., Dinglasan, L. A., Liu, N. Q., Sayre, J., Chiappelli, F., et al. (2004). Inflammation in amyotrophic lateral sclerosis spinal cord and brain is mediated by activated macrophages, mast cells and T cells. Amyotroph. Lateral Scler. Other Motor Neuron Disord. 5, 213-219. doi: 10.1080/14660820410020286.
55. Guil, S., and Caceres, J. F. (2007). The multifunctional RNA-binding protein hnRNP A1 is required for processing of miR-18a. Nat. Struct. Mol. Biol. 14, 591-596. doi: 10.1038/nsmb1250.
56. Hall, E. D., Oostveen, J. A., and Gurney, M. E. (1998). Relationship of microglial and astrocytic activation to disease onset and progression in a transgenic model of familial ALS. Glia 23, 249-256. doi: 10.1002/(SICI)1098-1136(199807)23:3<249::AID-GLIA7>3.0.CO;2-#.
57. Hanisch, U. K., and Kettenmann, H. (2007). Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat. Neurosci. 10, 1387-1394. doi: 10.1038/nn1997.
58. Haramati, S., Chapnik, E., Sztainberg, Y., Eilam, R., Zwang, R., Gershoni, N., et al. (2010). miRNA malfunction causes spinal motor neuron disease. Proc. Natl. Acad. Sci. U.S.A. 107, 13111-13116. doi: 10.1073/pnas.1006151107.
59. Henkel, J. S., Beers, D. R., Wen, S., Rivera, A. L., Toennis, K. M., Appel, J. E., et al. (2013). Regulatory T-lymphocytes mediate amyotrophic lateral sclerosis progression and survival. EMBO Mol. Med. 5, 64-79. doi: 10.1002/emmm.201201544.
60. Heurich, B., El Idrissi, N. B., Donev, R. M., Petri, S., Claus, P., Neal, J., et al. (2011). Complement upregulation and activation on motor neurons and neuromuscular junction in the SOD1 G93A mouse model of familial amyotrophic lateral sclerosis. J. Neuroimmunol. 235, 104-109. doi: 10.1016/j.jneuroim.2011.03.011.
61. Hohlfeld, R., Kerschensteiner, M., Stadelmann, C., Lassmann, H., and Wekerle, H. (2000). The neuroprotective effect of inflammation: implications for the therapy of multiple sclerosis. J. Neuroimmunol. 107, 161-166. doi: 10.1016/S0165-5728(00)00233-2.
62. Ilzecka, J. (2011). Granzymes A and B levels in serum of patients with amyotrophic lateral sclerosis. Clin. Biochem. 44, 650-653. doi: 10.1016/j.clinbiochem.2011.02.006.
63. Inoue, K. (2006). The function of microglia through purinergic receptors: neuropathic pain and cytokine release. Pharmacol. Ther. 109, 210-226. doi: 10.1016/j.pharmthera.2005.07.001.
64. Ito, Y., Yamada, M., Tanaka, H., Aida, K., Tsuruma, K., Shimazawa, M., et al. (2009). Involvement of CHOP, an ER-stress apoptotic mediator, in both human sporadic ALS and ALS model mice. Neurobiol. Dis. 36, 470-476. doi: 10.1016/j.nbd.2009.08.013.
65. Kaur, G., Trowsdale, J., and Fugger, L. (2012). Natural killer cells and their receptors in multiple sclerosis. Brain 136(Pt 9), 2657-2676. doi: 10.1093/brain/aws159.
66. Kawamata, T., Akiyama, H., Yamada, T., and McGeer, P. L. (1992). Immunologic reactions in amyotrophic lateral sclerosis brain and spinal cord tissue. Am. J. Pathol.140, 691-707.
67. Kawahara, Y., and Mieda-Sato, A. (2012). TDP-43 promotes microRNA biogenesis as a component of the Drosha and Dicer complexes. Proc. Natl. Acad. Sci. U.S.A. 109, 3347-3352. doi: 10.1073/pnas.1112427109.
68. Kawahara, K., Oyadomari, S., Gotoh, T., Kohsaka, S., Nakayama, H., and Mori, M. (2001). Induction of CHOP and apoptosis by nitric oxide in p53-deficient microglial cells. FEBS Lett. 506, 135-139. doi: 10.1016/S0014-5793(01)02898-8.
69. Kerschensteiner, M., Gallmeier, E., Behrens, L., Leal, V. V., Misgeld, T., Klinkert, W. E., et al. (1999). Activated human T cells, B cells, and monocytes produce brain-derived neurotrophic factor in vitro and in inflammatory brain lesions: a neuroprotective role of inflammation? J. Exp. Med. 189, 865-870. doi: 10.1084/jem.189.5.865.
70. Kim, H. J., Kim, N. C., Wang, Y. D., Scarborough, E. A., Moore, J., Diaz, Z., et al. (2013). Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS. Nature 495, 467-473. doi: 10.1038/nature11922.
71. Lacroix, S., Feinstein, D., and Rivest, S. (1998). The bacterial endotoxin lipopolysaccharide has the ability to target the brain in upregulating its membrane CD14 receptor within specific cellular populations. Brain Pathol. 8, 625-640. doi: 10.1111/j.1750-3639.1998.tb00189.x.
72. Laflamme, N., and Rivest, S. (2001). Toll-like receptor 4: the missing link of the cerebral innate immune response triggered by circulating gram-negative bacterial cell wall components. FASEB J. 15, 155-163. doi: 10.1096/fj.00-0339com.
73. Laflamme, N., Soucy, G., and Rivest, S. (2001). Circulating cell wall components derived from gram-negative, not gram-positive, bacteria cause a profound induction of the gene-encoding Toll-like receptor 2 in the CNS. J. Neurochem. 79, 648-657. doi: 10.1046/j.1471-4159.2001.00603.x.
74. Lautenschlaeger, J., Prell, T., and Grosskreutz, J. (2012). Endoplasmic reticulum stress and the ER mitochondrial calcium cycle in amyotrophic lateral sclerosis. Amyotroph. Lateral Scler. 13, 166-177. doi: 10.3109/17482968.2011.641569.
75. Lerman, B. J., Hoffman, E. P., Sutherland, M. L., Bouri, K., Hsu, D. K., Liu, F. T., et al. (2012). 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. 2, 563-575. doi: 10.1002/brb3.75.
76. Lewis, C. A., Manning, J., Rossi, F., and Krieger, C. (2012). The neuroinflammatory response in ALS: the roles of microglia and T cells. Neurol. Res. Int. 2012, 803701. doi: 10.1155/2012/803701.
77. Liao, B., Zhao, W., Beers, D. R., Henkel, J. S., and Appel, S. H. (2012). Transformation from a neuroprotective to a neurotoxic microglial phenotype in a mouse model of ALS. Exp. Neurol. 237, 147-152. doi: 10.1016/j.expneurol.2012.06.011.
78. Liu, Y., Hao, W., Dawson, A., Liu, S., and Fassbender, K. (2009). Expression of amyotrophic lateral sclerosis-linked SOD1 mutant increases the neurotoxic potential of microglia via TLR2. J. Biol. Chem. 284, 3691-3699. doi: 10.1074/jbc.M804446200.
79. Maekawa, S., Al-Sarraj, S., Kibble, M., Landau, S., Parnavelas, J., Cotter, D., et al. (2004). Cortical selective vulnerability in motor neuron disease: a morphometric study. Brain 127, 1237-1251. doi: 10.1093/brain/awh132.
80. Maruyama, H., Morino, H., Ito, H., Izumi, Y., Kato, H., Watanabe, Y., et al. (2010). Mutations of optineurin in amyotrophic lateral sclerosis. Nature 465, 223-226. doi: 10.1038/nature08971.
81. McCombe, P. A., and Henderson, R. D. (2011). The role of immune and inflammatory mechanisms in ALS. Curr. Mol. Med. 11, 246-254. doi: 10.2174/156652411795243450.
82. Norling, L. V., Perretti, M., and Cooper, D. (2009). Endogenous galectins and the control of the host inflammatory response. J. Endocrinol. 201, 169-184. doi: 10.1677/JOE-08-0512.
83. Nwosu, V. K., Royer, J. A., and Stickler, D. E. (2010). Voltage gated potassium channel antibodies in amyotrophic lateral sclerosis. Amyotroph. Lateral Scler. 11, 392-394. doi: 10.3109/17482960903452283.
84. O'Connell, R. M., Rao, D. S., and Baltimore, D. (2012). microRNA regulation of inflammatory responses. Annu. Rev. Immunol. 30, 295-312. doi: 10.1146/annurev-immunol-020711-075013.
85. Otsmane, B., Aebischer, J., Moumen, A., and Raoul, C. (2013). Cerebrospinal fluid-targeted delivery of neutralizing anti-IFNgamma antibody delays motor decline in an ALS mouse model. Neuroreport doi: 10.1097/WNR.0000000000000043 [Epub ahead of print].
86. Oyadomari, S., and Mori, M. (2004). Roles of CHOP/GADD153 in endoplasmic reticulum stress. Cell Death Differ. 11, 381-389. doi: 10.1038/sj.cdd.4401373.
87. Pagani, M. R., Reisin, R. C., and Uchitel, O. D. (2006). Calcium signaling pathways mediating synaptic potentiation triggered by amyotrophic lateral sclerosis IgG in motor nerve terminals. J. Neurosci. 26, 2661-2672. doi: 10.1523/JNEUROSCI.4394-05.2006.
88. Panzara, M. A., Gussoni, E., Begovich, A. B., Murray, R. S., Zang, Y. Q., Appel, S. H., et al. (1999). T cell receptor BV gene rearrangements in the spinal cords and cerebrospinal fluid of patients with amyotrophic lateral sclerosis. Neurobiol. Dis. 6, 392-405. doi: 10.1006/nbdi.1999.0252.
89. Peter, M. E., Budd, R. C., Desbarats, J., Hedrick, S. M., Hueber, A. O., Newell, M. K., et al. (2007). The CD95 receptor: apoptosis revisited. Cell 129, 447-450. doi: 10.1016/j.cell.2007.04.031.
90. Petri, S., Kiaei, M., Wille, E., Calingasan, N. Y., and Flint Beal, M. (2006). Loss of Fas ligand-function improves survival in G93A-transgenic ALS mice. J. Neurol. Sci. 251, 44-49. doi: 10.1016/j.jns.2006.08.013.
91. Petri, S., Krampfl, K., Hashemi, F., Grothe, C., Hori, A., Dengler, R., et al. (2003). Distribution of GABAA receptor mRNA in the motor cortex of ALS patients. J. Neuropathol. Exp. Neurol. 62, 1041-1051.
92. Petrik, M. S., Wilson, J. M., Grant, S. C., Blackband, S. J., Tabata, R. C., Shan, X., et al. (2007). Magnetic resonance microscopy and immunohistochemistry of the CNS of the mutant SOD murine model of ALS reveals widespread neural deficits. Neuromol. Med.9, 216-229. doi: 10.1007/s12017-007-8002-1.
93. Philips, T., and Robberecht, W. (2011). Neuroinflammation in amyotrophic lateral sclerosis: role of glial activation in motor neuron disease. Lancet Neurol. 10, 253-263. doi: 10.1016/S1474-4422(11)70015-1.
94. Piani, D., and Fontana, A. (1994). Involvement of the cystine transport system xc-in the macrophage-induced glutamate-dependent cytotoxicity to neurons. J. Immunol.152, 3578-3585.
95. Polymenidou, M., Lagier-Tourenne, C., Hutt, K. R., Huelga, S. C., Moran, J., Liang, T. Y., et al. (2011). Long pre-mRNA depletion and RNA missplicing contribute to neuronal vulnerability from loss of TDP-43. Nat. Neurosci. 14, 459-468. doi: 10.1038/nn.2779.
96. Pool, M., Rambaldi, I., Darlington, P. J., Wright, M. C., Fournier, A. E., and Bar-or, A. (2012). Neurite outgrowth is differentially impacted by distinct immune cell subsets. Mol. Cell. Neurosci. 49, 68-76. doi: 10.1016/j.mcn.2011.09.004.
97. Qin, S., Colin, C., Hinners, I., Gervais, A., Cheret, C., and Mallat, M. (2006). System Xc-and apolipoprotein E expressed by microglia have opposite effects on the neurotoxicity of amyloid-beta peptide 1-40. J. Neurosci. 26, 3345-3356. doi: 10.1523/JNEUROSCI.5186-05.2006.
98. Raoul, C., Buhler, E., Sadeghi, C., Jacquier, A., Aebischer, P., Pettmann, B., et al. (2006). Chronic activation in presymptomatic amyotrophic lateral sclerosis (ALS) mice of a feedback loop involving Fas, Daxx, and FasL. Proc. Natl. Acad. Sci. U.S.A.103, 6007-6012. doi: 10.1073/pnas.0508774103.
99. Raoul, C., Estevez, A. G., Nishimune, H., Cleveland, D. W., Delapeyriere, O., Henderson, C. E., et al. (2002). Motoneuron death triggered by a specific pathway downstream of Fas. Potentiation by ALS-linked SOD1 mutations. Neuron 35, 1067-1083. doi: 10.1016/S0896-6273(02)00905-4.
100. Raoul, C., Henderson, C. E., and Pettmann, B. (1999). Programmed cell death of embryonic motoneurons triggered through the Fas death receptor. J. Cell Biol. 147, 1049-1062. doi: 10.1083/jcb.147.5.1049.
101. Rentzos, M., Evangelopoulos, E., Sereti, E., Zouvelou, V., Marmara, S., Alexakis, T., et al. (2012). Alterations of T cell subsets in ALS: a systemic immune activation? Acta Neurol. Scand. 125, 260-264. doi: 10.1111/j.1600-0404.2011.01528.x.
102. Rentzos, M., Nikolaou, C., Rombos, A., Boufidou, F., Zoga, M., Dimitrakopoulos, A., et al. (2007). RANTES levels are elevated in serum and cerebrospinal fluid in patients with amyotrophic lateral sclerosis. Amyotroph. Lateral Scler. 8, 283-287. doi: 10.1080/17482960701419232.
103. Rentzos, M., Rombos, A., Nikolaou, C., Zoga, M., Zouvelou, V., Dimitrakopoulos, A., et al. (2010). Interleukin-17 and interleukin-23 are elevated in serum and cerebrospinal fluid of patients with ALS: a reflection of Th17 cells activation? Acta Neurol. Scand.122, 425-429. doi: 10.1111/j.1600-0404.2010.01333.x.
104. Reynolds, A. D., Banerjee, R., Liu, J., Gendelman, H. E., and Mosley, R. L. (2007). Neuroprotective activities of CD4+CD25+ regulatory T cells in an animal model of Parkinson's disease. J. Leukoc. Biol. 82, 1083-1094. doi: 10.1189/jlb.0507296.
105. - co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation. Nature 397, 251-255. doi: 10.1038/16697.
106. Rosas-Ballina, M., Olofsson, P. S., Ochani, M., Valdes-Ferrer, S. I., Levine, Y. A., Reardon, C., et al. (2011). Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit. Science 334, 98-101. doi: 10.1126/science.1209985.
107. Rowland, L. P., and Shneider, N. A. (2001). Amyotrophic lateral sclerosis. N. Engl. J. Med. 344, 1688-1700. doi: 10.1056/NEJM200105313442207.
108. Sanagi, T., Yuasa, S., Nakamura, Y., Suzuki, E., Aoki, M., Warita, H., et al. (2010). Appearance of phagocytic microglia adjacent to motoneurons in spinal cord tissue from a presymptomatic transgenic rat model of amyotrophic lateral sclerosis. J. Neurosci. Res. 88, 2736-2746. doi: 10.1002/jnr.22424.
109. Saxena, S., Cabuy, E., and Caroni, P. (2009). A role for motoneuron subtype-selective ER stress in disease manifestations of FALS mice. Nat. Neurosci. 12, 627-636. doi: 10.1038/nn.2297.
110. Schutz, B., Reimann, J., Dumitrescu-Ozimek, L., Kappes-Horn, K., Landreth, G. E., Schurmann, B., et al. (2005). The oral antidiabetic pioglitazone protects from neurodegeneration and amyotrophic lateral sclerosis-like symptoms in superoxide dismutase-G93A transgenic mice. J. Neurosci. 25, 7805-7812. doi: 10.1523/JNEUROSCI.2038-05.2005.
111. Schwartz, M., and Moalem, G. (2001). Beneficial immune activity after CNS injury: prospects for vaccination. J. Neuroimmunol. 113, 185-192. doi: 10.1016/S0165-5728(00)00447-1.
112. Seksenyan, A., Ron-Harel, N., Azoulay, D., Cahalon, L., Cardon, M., Rogeri, P., et al. (2010). Thymic involution, a co-morbidity factor in amyotrophic lateral sclerosis. J. Cell Mol. Med. 14, 2470-2482. doi: 10.1111/j.1582-4934.2009.00863.x.
113. Sengun, I. S., and Appel, S. H. (2003). Serum anti-Fas antibody levels in amyotrophic lateral sclerosis. J. Neuroimmunol. 142, 137-140. doi: 10.1016/S0165-5728(03)00263-7.
114. Stommel, E. W., Cohen, J. A., Fadul, C. E., Cogbill, C. H., Graber, D. J., Kingman, L., et al. (2009). Efficacy of thalidomide for the treatment of amyotrophic lateral sclerosis: a phase II open label clinical trial. Amyotroph. Lateral Scler. 10, 393-404. doi: 10.3109/17482960802709416.
115. Sun, Y., Li, Q., Gui, H., Xu, D. P., Yang, Y. L., Su, D. F., et al. (2013). MicroRNA-124 mediates the cholinergic anti-inflammatory action through inhibiting the production of pro-inflammatory cytokines. Cell Res. doi: 10.1038/cr.2013.116 [Epub ahead of print].
116. Swarup, V., Phaneuf, D., Dupre, N., Petri, S., Strong, M., Kriz, J., et al. (2011). Deregulation of TDP-43 in amyotrophic lateral sclerosis triggers nuclear factor kappaB-mediated pathogenic pathways. J. Exp. Med. 208, 2429-2447. doi: 10.1084/jem.20111313.
117. Ugolini, G., Raoul, C., Ferri, A., Haenggeli, C., Yamamoto, Y., Salaun, D., et al. (2003). Fas/tumor necrosis factor receptor death signaling is required for axotomy-induced death of motoneurons in vivo. J. Neurosci. 23, 8526-8531.
118. van Domselaar, R., and Bovenschen, N. (2011). Cell death-independent functions of granzymes: hit viruses where it hurts. Rev. Med. Virol. doi: 10.1002/rmv.697 [Epub ahead of print].
119. Wang, L., Sharma, K., Grisotti, G., and Roos, R. P. (2009). The effect of mutant SOD1 dismutase activity on non-cell autonomous degeneration in familial amyotrophic lateral sclerosis. Neurobiol. Dis. 35, 234-240. doi: 10.1016/j.nbd.2009.05.002.
120. Weydt, P., Yuen, E. C., Ransom, B. R., and Moller, T. (2004). Increased cytotoxic potential of microglia from ALS-transgenic mice. Glia 48, 179-182. doi: 10.1002/glia.20062.
121. Wilson, R. C., and Doudna, J. A. (2013). Molecular mechanisms of RNA interference. Annu. Rev. Biophys. 42, 217-239. doi: 10.1146/annurev-biophys-083012-130404.
122. Woodruff, T. M., Costantini, K. J., Crane, J. W., Atkin, J. D., Monk, P. N., Taylor, S. M., et al. (2008). The complement factor C5a contributes to pathology in a rat model of amyotrophic lateral sclerosis. J. Immunol. 181, 8727-8734.
123. Yamanaka, K., Chun, S. J., Boillee, S., Fujimori-Tonou, N., Yamashita, H., Gutmann, D. H., et al. (2008). Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis. Nat. Neurosci. 11, 251-253. doi: 10.1038/nn2047.
124. Yi, F. H., Lautrette, C., Vermot-Desroches, C., Bordessoule, D., Couratier, P., Wijdenes, J., et al. (2000). In vitro induction of neuronal apoptosis by anti-Fas antibody-containing sera from amyotrophic lateral sclerosis patients. J. Neuroimmunol. 109, 211-220. doi: 10.1016/S0165-5728(00)00288-5.
125. Yiangou, Y., Facer, P., Durrenberger, P., Chessell, I. P., Naylor, A., Bountra, C., et al. (2006). COX-2, CB2 and P2X7-immunoreactivities are increased in activated microglial cells/macrophages of multiple sclerosis and amyotrophic lateral sclerosis spinal cord. BMC Neurol. 6:12. doi: 10.1186/1471-2377-6-12.
126. Zhang, N., and Bevan, M. J. (2011). CD8(+) T cells: foot soldiers of the immune system. Immunity 35, 161-168. doi: 10.1016/j.immuni.2011.07.010.
127. Zhang, R., Gascon, R., Miller, R. G., Gelinas, D. F., Mass, J., Hadlock, K., et al. (2005). Evidence for systemic immune system alterations in sporadic amyotrophic lateral sclerosis (sALS). J. Neuroimmunol. 159, 215-224. doi: 10.1016/j.jneuroim.2004.10.009.
128. Zhang, R., Miller, R. G., Gascon, R., Champion, S., Katz, J., Lancero, M., et al. (2009). Circulating endotoxin and systemic immune activation in sporadic amyotrophic lateral sclerosis (sALS). J. Neuroimmunol. 206, 121-124. doi: 10.1016/j.jneuroim.2008.09.017.
129. Zhao, W., Beers, D. R., Henkel, J. S., Zhang, W., Urushitani, M., Julien, J. P., et al. (2010). Extracellular mutant SOD1 induces microglial-mediated motoneuron injury. Glia 58, 231-243. doi: 10.1002/glia.20919.
130. Zhao, W., Beers, D. R., Liao, B., Henkel, J. S., and Appel, S. H. (2012). Regulatory T lymphocytes from ALS mice suppress microglia and effector T lymphocytes through different cytokine-mediated mechanisms. Neurobiol. Dis. 48, 418-428. doi: 10.1016/j.nbd.2012.07.008.