Inflammation in ALS and SMA: Sorting out the good from the evil

Neurobiology of Disease

Volumn 37, Issue 3, 2010, Pages 493-502

  Papadimitriou, Dimitra ^a,b   Le Verche, Virginia ^a,b   Jacquier, Arnaud ^a,b   Ikiz, Burcin ^a,b   Przedborski, Serge ^a,b   Re, Diane B ^a,b  

^a Department of Neurology ^*  (United States)

^b Center for Motor Neuron Biology and Disease   (United States)

Author keywords

Amyotrophic lateral sclerosis (ALS); Astrocytes; Astrocytosis; Gliosis; Microglia; Microgliosis; Neuroinflammation; Spinal muscular atrophy (SMA); Superoxide dismutase 1 (SOD1)

Indexed keywords

BUTYRIC ACID; CARDIOTROPHIN 1; CD11B ANTIGEN; GAMMA INTERFERON; GLIAL FIBRILLARY ACIDIC PROTEIN; HISTONE DEACETYLASE INHIBITOR; INDUCIBLE NITRIC OXIDE SYNTHASE; INTERLEUKIN 1BETA; INTERLEUKIN 6; NEUROTROPHIN RECEPTOR P75; RILUZOLE; SUPEROXIDE DISMUTASE; SURVIVAL MOTOR NEURON PROTEIN 1; SURVIVAL MOTOR NEURON PROTEIN 2; TRICHOSTATIN A; TUMOR NECROSIS FACTOR ALPHA; VALPROIC ACID;

AMYOTROPHIC LATERAL SCLEROSIS; ASTROCYTE; CELL INTERACTION; CHROMOSOME 5Q; CLINICAL TRIAL; DEGENERATIVE DISEASE; DISEASE COURSE; GLIOSIS; HUMAN; INNATE IMMUNITY; MICROGLIA; MOTOR NEURON DISEASE; NERVOUS SYSTEM INFLAMMATION; NEUROPROTECTION; PHAGOCYTOSIS; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; SPINAL MUSCULAR ATROPHY;

AMYOTROPHIC LATERAL SCLEROSIS; ASTROCYTES; CYTOPROTECTION; GLIOSIS; HUMANS; MICROGLIA; MUSCULAR ATROPHY, SPINAL; MYELITIS; NERVE DEGENERATION; NEUROGLIA; SUPEROXIDE DISMUTASE;

EID: 75949107667     PISSN: 09699961     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.nbd.2009.10.005     Document Type: Review

References (139)

1. Almer G., Vukosavic S., Romero N., and Przedborski S. Inducible nitric oxide synthase upregulation in a transgenic mouse model of familial amyotrophic lateral sclerosis. J. Neurochem. 72 (1999) 2415-2425
2. Almer G., Guégan C., Teismann P., Naini A., Rosoklija G., Hays A.P., Chen C., and Przedborski S. Increased expression of the pro-inflammatory enzyme cyclooxygenase-2 in amyotrophic lateral sclerosis. Ann. Neurol. 49 (2001) 176-185
3. Apostolski S., Nikolic J., Bugarskiprokopljevic C., Miletic V., Pavlovic S., and Filipovic S. Serum and CSF immunological findings in ALS. Acta Neurol. Scand. 83 (1991) 96-98
4. Araki S., Hayashi M., Tamagawa K., Saito M., Kato S., Komori T., Sakakihara Y., Mizutani T., and Oda A. Neuropathological analysis in spinal muscular atrophy type II. Acta Neuropathol. 106 (2003) 441-448
5. Banerjee R., Mosley R.L., Reynolds A.D., Dhar A., Jackson-Lewis V., Gordon P.H., Przedborski S., and Gendelman H.E. Adaptive immune neuroprotection in G93A-SOD1 amyotrophic lateral sclerosis mice. PLoS ONE 3 (2008) e2740
6. Beckman J.S., and Koppenol W.H. Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and the ugly. Am. J. Physiol., Cell Physiol. 271 (1996) C1424-C1437
7. Beers D.R., Henkel J.S., Xiao Q., Zhao W., Wang J., Yen A.A., Siklos L., McKercher S.R., and Appel S.H. Wild-type microglia extend survival in PU.1 knockout mice with familial amyotrophic lateral sclerosis. Proc. Natl. Acad. Sci. U. S. A. 103 (2006) 16021-16026
8. + 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 (2008) 15558-15563
9. Bogdanov M.B., Ramos L.E., Xu Z.S., and Beal M.F. Elevated "hydroxyl radical" generation in vivo in an animal model of amyotrophic lateral sclerosis. J. Neurochem. 71 (1998) 1321-1324
10. Boillee S., Yamanaka K., Lobsiger C.S., Copeland N.G., Jenkins N.A., Kassiotis G., Kollias G., and Cleveland D.W. Onset and progression in inherited ALS determined by motor neurons and microglia. Science 312 (2006) 1389-1392
11. Bordet T., Schmalbruch H., Pettmann B., Hagege A., Castelnau-Ptakhine L., Kahn A., and Haase G. Adenoviral cardiotrophin-1 gene transfer protects pmn mice from progressive motor neuronopathy. J. Clin. Invest. 104 (1999) 1077-1085
12. Bordet T., Lesbordes J.C., Rouhani S., Castelnau-Ptakhine L., Schmalbruch H., Haase G., and Kahn A. Protective effects of cardiotrophin-1 adenoviral gene transfer on neuromuscular degeneration in transgenic ALS mice. Hum. Mol. Genet. 10 (2001) 1925-1933
13. Bruijn L.I., Becher M.W., Lee M.K., Anderson K.L., Jenkins N.A., Copeland N.G., Sisodia S., Rothstein J.D., Borchelt D.R., Price D.L., and Cleveland D.W. ALS-linked SOD1 mutant G85R mediated damage to astrocytes and promotes rapidly progressive disease with SOD1-containing inclusions. Neuron 18 (1997) 327-338
14. Bruijn L.I., Miller T.M., and Cleveland D.W. Unraveling the mechanisms involved in motor neuron degeneration in ALS. Annu. Rev. Neurosci. 27 (2004) 723-749
15. Cardona, A.E., Pioro, E.P., Sasse, M.E., Kostenko, V., Cardona, S.M., Dijkstra, I.M., Huang, D.R., Kidd, G., Dombrowski, S., Dutta, R.J., Lee, J.C., Cook, D.N., Jung, S., Lira, S.A., Littman, D.R., Ransohoff, R.M. 2006. Control of microglial neurotoxicity by the fractalkine receptor. Nat. Neurosci. 9, 917-924.
16. Cassina P., Peluffo H., Pehar M., Martinez-Palma L., Ressia A., Beckman J.S., Estevez A.G., and Barbeito L. Peroxynitrite triggers a phenotypic transformation in spinal cord astrocytes that induces motor neuron apoptosis. J. Neurosci. Res. 67 (2002) 21-29
17. Chalmers G.R., Peterson D.A., and Gage F.H. Sprouting adult CNS cholinergic axons express nile and associate with astrocytic surfaces expressing neural cell adhesion molecule. J. Comp. Neurol. 371 (1996) 287-299
18. Chavany C., Vicario-Abejon C., Miller G., and Jendoubi M. Transgenic mice for interleukin 3 develop motor neuron degeneration associated with autoimmune reaction against spinal cord motor neurons. Proc. Natl. Acad. Sci. U. S. A. 95 (1998) 11354-11359
19. Chen P.S., Wang C.C., Bortner C.D., Peng G.S., Wu X., Pang H., Lu R.B., Gean P.W., Chuang D.M., and Hong J.S. Valproic acid and other histone deacetylase inhibitors induce microglial apoptosis and attenuate lipopolysaccharide-induced dopaminergic neurotoxicity. Neuroscience 149 (2007) 203-212
20. Chou S.M., and Fakadej A.V. Ultrastructure of chromatolytic motoneurons and anterior spinal roots in a case of Werdnig-Hoffmann disease. J. Neuropathol. Exp. Neurol. 30 (1971) 368-&
21. Chou S.M., and Nonaka I. Werdnig-Hoffmann disease-proposal of a pathogenetic mechanism. Acta Neuropathol. 41 (1978) 45-54
22. Clement A.M., Nguyen M.D., Roberts E.A., Garcia M.L., Boillee S., Rule M., McMahon A.P., Doucette W., Siwek D., Ferrante R.J., Brown Jr. R.H., Julien J.P., Goldstein L.S.B., and Cleveland D.W. Wild-type nonneuronal cells extend survival of SOD1 mutant motor neurons in ALS mice. Science 302 (2003) 113-117
23. Di Giorgio F.P., Carrasco M.A., Siao M.C., Maniatis T., and Eggan K. Non-cell autonomous effect of glia on motor neurons in an embryonic stem cell-based ALS model. Nat. Neurosci. 10 (2007) 608-614
24. Di Giorgio F.P., Boulting G.L., Bobrowicz S., and Eggan K.C. Human embryonic stem cell-derived motor neurons are sensitive to the toxic effect of glial cells carrying an ALS-causing mutation. Cell Stem Cell 3 (2008) 637-648
25. Domeniconi M., Hempstead B.L., and Chao M.V. Pro-NGF secreted by astrocytes promotes motor neuron cell death. Mol. Cell. Neurosci. 34 (2007) 271-279
26. Dong Y., and Benveniste E.N. Immune function of astrocytes. Glia 36 (2001) 180-190
27. Drachman D.B., Frank K., Dykes-Hoberg M., Teismann P., Almer G., Przedborski S., and Rothstein J.D. Cyclooxygenase 2 inhibition protects motor neurons and prolongs survival in a transgenic mouse model of ALS. Ann. Neurol. 52 (2002) 771-778
28. Elliott J.L. Cytokine upregulation in a murine model of familial amyotrophic lateral sclerosis. Brain Res. Mol. Brain Res. 95 (2001) 172-178
29. Estévez A.G., Spear N., Manuel S.M., Radi R., Henderson C.E., Barbeito L., and Beckman J.S. Nitric oxide and superoxide contribute to motor neuron apoptosis induced by trophic factor deprivation. J. Neurosci. 18 (1998) 923-931
30. Farina C., Aloisi F., and Meinl E. Astrocytes are active players in cerebral innate immunity. Trends Immunol. 28 (2007) 138-145
31. Feldkotter M., Schwarzer V., Wirth R., Wienker T.F., and Wirth B. Quantitative analyses of SMN1 and SMN2 based on real-time lightCycler PCR: fast and highly reliable carrier testing and prediction of severity of spinal muscular atrophy. Am. J. Hum. Genet. 70 (2002) 358-368
32. Ferrante R.J., Shinobu L.A., Schulz J.B., Matthews R.T., Thomas C.E., Kowall N.W., Gurney M.E., and Beal M.F. Increased 3-nitrotyrosine and oxidative damage in mice with a human copper/zinc superoxide dismutase mutation. Ann. Neurol. 42 (1997) 326-334
33. Fischer L.R., Culver D.G., Tennant P., Davis A.A., Wang M., Castellano-Sanchez A., Khan J., Polak M.A., and Glass J.D. Amyotrophic lateral sclerosis is a distal axonopathy: evidence in mice and man. Exp. Neurol. 185 (2004) 232-240
34. Flugel A., Bradl M., Kreutzberg G.W., and Graeber M.B. Transformation of donor-derived bone marrow precursors into host microglia during autoimmune CNS inflammation and during the retrograde response to axotomy. J. Neurosci. Res. 66 (2001) 74-82
35. Friedlander R.M., Brown R.H., Gagliardini V., Wang J., and Yuan J. Inhibition of ICE slows ALS in mice. Nature 388 (1997) 31
36. Frugier T., Nicole S., Cifuentes-Diaz C., and Melki J. The molecular bases of spinal muscular atrophy. Curr. Opin. Genet. Dev. 12 (2002) 294-298
37. Garbuzova-Davis S., Saporta S., Haller E., Kolomey I., Bennett S.P., Potter H., and Sanberg P.R. Evidence of compromised blood-spinal cord barrier in early and late symptomatic SOD1 mice modeling ALS. PLoS ONE 2 (2007) e1205
38. Garcia-Cabezas M.A., Garcia-Alix A., Martin Y., Gutierrez M., Hernandez C., Rodriguez J.I., and Morales C. Neonatal spinal muscular atrophy with multiple contractures, bone fractures, respiratory insufficiency and 5q13 deletion. Acta Neuropathol. 107 (2004) 475-478
39. Garcia-Estrada J., Garcia-Segura L.M., and Torres-Aleman I. Expression of insulin-like growth factor I by astrocytes in response to injury. Brain Res. 592 (1992) 343-347
40. Ghatak N.R. Glial bundles in spinal nerve roots-a form of isomorphic gliosis at the junction of the central and peripheral nervous-system. Neuropathol. Appl. Neurobiol. 9 (1983) 391-401
41. Gong Y.H., Parsadanian A.S., Andreeva A., Snider W.D., and Elliott J.L. Restricted expression of G86R Cu/Zn superoxide dismutase in astrocytes results in astrocytosis but does not cause motoneuron degeneration. J. Neurosci. 20 (2000) 660-665
42. Gonzalez-Scarano F., and Baltuch G. Microglia as mediators of inflammatory and degenerative diseases. Annu. Rev. Neurosci. 22 219-40 (1999) 219-240
43. Gotz R., Karch C., Digby M.R., Troppmair J., Rapp U.R., and Sendtner M. The neuronal apoptosis inhibitory protein suppresses neuronal differentiation and apoptosis in PC12 cells. Hum. Mol. Genet. 9 (2000) 2479-2489
44. Gowing G., Philips T., Van Wijmeersch B., Audet J.N., Dewil M., Van den Bosch L., Billiau A.D., Robberecht W., and Julien J.P. Ablation of proliferating microglia does not affect motor neuron degeneration in amyotrophic lateral sclerosis caused by mutant superoxide dismutase. J. Neurosci. 28 (2008) 10234-10244
45. 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., Chen W., Zhai P., Sufit R.L., and Siddique T. Motor neuron degeneration in mice that express a human Cu, Zn superoxide dismutase mutation. Science 264 (1994) 1772-1775
46. Hall E.D., Oostveen J.A., and Gurney M.E. Relationship of microglial and astrocytic activation to disease onset and progression in a transgenic model of familial ALS. Glia 23 (1998) 249-256
47. Harraz M.M., Marden J.J., Zhou W., Zhang Y., Williams A., Sharov V.S., Nelson K., Luo M., Paulson H., Schoneich C., and Engelhardt J.F. SOD1 mutations disrupt redox-sensitive Rac regulation of NADPH oxidase in a familial ALS model. J. Clin. Invest. 118 (2008) 659-670
48. Hayashi M., Araki S., Arai N., Kumada S., Itoh M., Tamagawa K., Oda M., and Morimatsu Y. Oxidative stress and disturbed glutamate transport in spinal muscular atrophy. Brain Dev. 24 (2002) 770-775
49. He B.P., Wen W.Y., and Strong M.J. Activated microglia (BV-2) facilitation of TNF-alpha-mediated motor neuron death in vitro. J. Neuroimmunol. 128 (2002) 31-38
50. Henkel J.S., Beers D.R., Siklos L., and Appel S.H. The chemokine MCP-1 and the dendritic and myeloid cells it attracts are increased in the mSOD1 mouse model of ALS. Mol. Cell. Neurosci. 31 (2006) 427-437
51. Hensley K., Floyd R.A., Gordon B., Mou S., Pye Q.N., Stewart C., West M., and Williamson K. Temporal patterns of cytokine and apoptosis-related gene expression in spinal cords of the G93A-SOD1 mouse model of amyotrophic lateral sclerosis. J. Neurochem. 82 (2002) 365-374
52. Hensley K., bdel-Moaty H., Hunter J., Mhatre M., Mou S., Nguyen K., Potapova T., Pye Q.N., Qi M., Rice H., Stewart C., Stroukoff K., and West M. Primary glia expressing the G93A-SOD1 mutation present a neuroinflammatory phenotype and provide a cellular system for studies of glial inflammation. J. Neuroinflammation. 3 (2006) 2
53. Hirano A. Neuropathology of ALS: an overview. Neurology 47 (1996) S63-S66
54. Imura T., Kornblum H.I., and Sofroniew M.V. The predominant neural stem cell isolated from postnatal and adult forebrain but not early embryonic forebrain expresses GFAP. J. Neurosci. 23 (2003) 2824-2832
55. Ince P.G., Shaw P.J., Slade J.Y., Jones C., and Hudgson P. Familial amyotrophic lateral sclerosis with a mutation in exon 4 of the Cu/Zn superoxide dismutase gene: pathological and immunocytochemical changes. Acta. Neuropathol. (Berl) 92 (1996) 395-403
56. Kang J., and Rivest S. MyD88-deficient bone marrow cells accelerate onset and reduce survival in a mouse model of amyotrophic lateral sclerosis. J. Cell Biol. 179 (2007) 1219-1230
57. Kariya S., Park G.H., Maeno-Hikichi Y., Leykekhman O., Lutz C., Arkovitz M.S., Landmesser L.T., and Monani U.R. Reduced SMN protein impairs maturation of the neuromuscular junctions in mouse models of spinal muscular atrophy. Hum. Mol. Genet. 17 (2008) 2552-2569
58. Kawamata T., Akiyama H., Yamada T., and McGeer P.L. Immunologic reactions in amyotrophic lateral sclerosis brain and spinal cord tissue. Am. J. Pathol. 140 (1992) 691-707
59. Kiaei M., Kipiani K., Petri S., Choi D.K., Chen J., Calingasan N.Y., and Beal M.F. Integrative role of cPLA with COX-2 and the effect of non-steriodal anti-inflammatory drugs in a transgenic mouse model of amyotrophic lateral sclerosis. J. Neurochem. 93 (2005) 403-411
60. Kihira T., Suzuki A., Kubo T., Miwa H., and Kondo T. Expression of insulin-like growth factor-II and leukemia inhibitory factor antibody immunostaining on the ionized calcium-binding adaptor molecule 1-positive microglias in the spinal cord of amyotrophic lateral sclerosis patients. Neuropathology 27 (2007) 257-268
61. Kim H.J., Rowe M., Ren M., Hong J.S., Chen P.S., and Chuang D.M. Histone deacetylase inhibitors exhibit anti-inflammatory and neuroprotective effects in a rat permanent ischemic model of stroke: multiple mechanisms of action. J. Pharmacol. Exp. Ther. 321 (2007) 892-901
62. Klebanoff S.J. Oxygen metabolites from phagocytes. In: Gallin J.I., Goldstein I.M., and Snydermann R. (Eds). Inflammation: Basic Principles and Clinical Correlates (1992), Raven, New York 541-588
63. Klivenyi P., Kiaei M., Gardian G., Calingasan N.Y., and Beal M.F. Additive neuroprotective effects of creatine and cyclooxygenase 2 inhibitors in a transgenic mouse model of amyotrophic lateral sclerosis. J. Neurochem. 88 (2004) 576-582
64. Kostic V., Jackson-Lewis V., De Bilbao F., Dubois-Dauphin M., and Przedborski S. Bcl-2: prolonging life in a transgenic mouse model of familial amyotrophic lateral sclerosis. Science 277 (1997) 559-562
65. Kreutzberg G.W. Microglia: a sensor for pathological events in the CNS. Trends Neurosci. 19 (1996) 312-318
66. Kriz J., Nguyen M.D., and Julien J.P. Minocycline slows disease progression in a mouse model of amyotrophic lateral sclerosis. Neurobiol. Dis. 10 (2002) 268-278
67. Kumagai T., and Hashizume Y. Morphological and morphometric studies on the spinal-cord lesion in Werdnig-Hoffmann disease. Brain Dev. 4 (1982) 87-96
68. Kuru S., Sakai M., Konagaya M., Yoshida M., Hashizume Y., and Saito K. An autopsy case of spinal muscular atrophy type III (Kugelberg-Welander disease). Neuropathology 29 (2009) 63-67
69. Le T.T., Pham L.T., Butchbach M.E., Zhang H.L., Monani U.R., Coovert D.D., Gavrilina T.O., Xing L., Bassell G.J., and Burghes A.H. SMNDelta7, the major product of the centromeric survival motor neuron (SMN2) gene, extends survival in mice with spinal muscular atrophy and associates with full-length SMN. Hum. Mol. Genet. 14 (2005) 845-857
70. Lefebvre S., Burglen L., Reboullet S., Clermont O., Burlet P., Viollet L., Benichou B., Cruaud C., Millasseau P., and Zeviani M. Identification and characterization of a spinal muscular atrophy-determining gene. Cell 80 (1995) 155-165
71. Lefebvre S., Burlet P., Liu Q., Bertrandy S., Clermont O., Munnich A., Dreyfuss G., and Melki J. Correlation between severity and SMN protein level in spinal muscular atrophy. Nat. Genet. 16 (1997) 265-269
72. Lepore A.C., Dejea C., Carmen J., Rauck B., Kerr D.A., Sofroniew M.V., and Maragakis N.J. Selective ablation of proliferating astrocytes does not affect disease outcome in either acute or chronic models of motor neuron degeneration. Exp. Neurol. 211 (2008) 423-432
73. Lesbordes J.C., Cifuentes-Diaz C., Miroglio A., Joshi V., Bordet T., Kahn A., and Melki J. Therapeutic benefits of cardiotrophin-1 gene transfer in a mouse model of spinal muscular atrophy. Hum. Mol. Genet. 12 (2003) 1233-1239
74. Lewis C.A., Solomon J.N., Rossi F.M., and Krieger C. Bone marrow-derived cells in the central nervous system of a mouse model of amyotrophic lateral sclerosis are associated with blood vessels and express CX(3)CR1. Glia (2009)
75. Li Y., and Raisman G. Sprouts from cut corticospinal axons persist in the presence of astrocytic scarring in long-term lesions of the adult-rat spinal-cord. Exp. Neurol. 134 (1995) 102-111
76. Li M., Ona V.O., Guégan C., Chen M., Jackson-Lewis V., Andrews L.J., Olszewski A.J., Stieg P.E., Lee J.P., Przedborski S., and Friedlander R.M. Functional role of caspase-1 and caspase-3 in an ALS transgenic mouse model. Science 288 (2000) 335-339
77. Liang X.B., Wang Q., Shi J., Lokteva L., Breyer R.M., Montine T.J., and Andreasson K. The prostaglandin E-2 EP2 receptor accelerates disease progression and inflammation in a model of amyotrophic lateral sclerosis. Ann. Neurol. 64 (2008) 304-314
78. Liu Y., Hao W., Dawson A., Liu S., and Fassbender K. Expression of amyotrophic lateral sclerosis-linked SOD1 mutant increases the neurotoxic potential of microglia via TLR2. J. Biol. Chem. 284 (2009) 3691-3699
79. Lorson C.L., Hahnen E., Androphy E.J., and Wirth B. A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy. Proc. Natl. Acad. Sci. U. S. A. 96 (1999) 6307-6311
80. MacMicking J., Xie Q.-W., and Nathan C. Nitric oxide and macrophage function. Annu. Rev. Immunol. 15 (1997) 323-350
81. Maihofner C., Probst-Cousin S., Bergmann M., Neuhuber W., Neundorfer B., and Heuss D. Expression and localization of cyclooxygenase-1 and -2 in human sporadic amyotrophic lateral sclerosis. Eur. J. Neurosci. 18 (2003) 1527-1534
82. Marchetto M.C., Muotri A.R., Mu Y., Smith A.M., Cezar G.G., and Gage F.H. Non-cell-autonomous effect of human SOD1 G37R astrocytes on motor neurons derived from human embryonic stem cells. Cell Stem Cell 3 (2008) 649-657
83. Mckeon R.J., Hoke A., and Silver J. Injury-induced proteoglycans inhibit the potential for laminin-mediated axon growth on astrocytic scars. Exp. Neurol. 136 (1995) 32-43
84. Millino C., Fanin M., Vettori A., Laveder P., Mostacciuolo M.L., Angelini C., and Lanfranchi G. Different atrophy-hypertrophy transcription pathways in muscles affected by severe and mild spinal muscular atrophy. BMC Med. (2009) 7
85. Moisse K., and Strong M.J. Innate immunity in amyotrophic lateral sclerosis. Biochim. Biophys. Acta Mol. Basis Dis. 1762 (2006) 1083-1093
86. Monani U.R., Coovert D.D., and Burghes A.H. Animal models of spinal muscular atrophy. Hum. Mol. Genet. 9 (2000) 2451-2457
87. Monani U.R., Sendtner M., Coovert D.D., Parsons D.W., Andreassi C., Le T.T., Jablonka S., Schrank B., Rossol W., Prior T.W., Morris G.E., and Burghes A.H. The human centromeric survival motor neuron gene (SMN2) rescues embryonic lethality in Smn(-/-) mice and results in a mouse with spinal muscular atrophy. Hum. Mol. Genet. 9 (2000) 333-339
88. Nagai M., Re D.B., Nagata T., Chalazonitis A., Jessell T.M., Wichterle H., and Przedborski S. Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons. Nat. Neurosci. 10 (2007) 615-622
89. Nakajima K., Tohyama Y., Kohsaka S., and Kurihara T. Microglia activated with ceramide enhance the secretion of brain-derived neurotrophic factor (BDNF) without induction of deleterious factors in vitro. Glia (2002) S91
90. Nguyen M.D., D'Aigle T., Gowing G., Julien J.P., and Rivest S. Exacerbation of motor neuron disease by chronic stimulation of innate immunity in a mouse model of amyotrophic lateral sclerosis. J. Neurosci. 24 (2004) 1340-1349
91. Parsons D.W., McAndrew P.E., Allinson P.S., Parker W.D., Burghes A.H.M., and Prior T.W. Diagnosis of spinal muscular atrophy in an SMN non-deletion patient using a quantitative PCR screen and mutation analysis. J. Med. Genet. 35 (1998) 674-676
92. Pasinelli P., and Brown R.H. Molecular biology of amyotrophic lateral sclerosis: insights from genetics. Nat. Rev., Neurosci. 7 (2006) 710-723
93. Pasinelli P., Borchelt D.R., Houseweart M.K., Cleveland D.W., and Brown R.H.J. Caspase-1 is activated in neural cells and tissue with amyotrophic lateral sclerosis-associated mutations in copper-zinc superoxide dismutase. Proc. Natl. Acad. Sci. U. S. A. 95 (1998) 15763-15768
94. Pearn J. Incidence, prevalence, and gene frequency studies of chronic childhood spinal muscular-atrophy. J. Med. Genet. 15 (1978) 409-413
95. Pedersen W.A., Fu W., Keller J.N., Markesbery W.R., Appel S., Smith R.G., Kasarskis E., and Mattson M.P. Protein modification by the lipid peroxidation product 4-hydroxynonenal in the spinal cords of amyotrophic lateral sclerosis patients. Ann. Neurol. 44 (1998) 819-824
96. Pehar M., Cassina P., Vargas M.R., Castellanos R., Viera L., Beckman J.S., Estevez A.G., and Barbeito L. Astrocytic production of nerve growth factor in motor neuron apoptosis: implications for amyotrophic lateral sclerosis. J. Neurochem. 89 (2004) 464-473
97. Pehar M., Vargas M.R., Cassina P., Barbeito A.G., Beckman J.S., and Barbeito L. Complexity of astrocyte-motor neuron interactions in amyotrophic lateral sclerosis. Neurodegener. Dis. 2 (2005) 139-146
98. Pehar M., Cassina P., Vargas M.R., Xie Y., Beckman J.S., Massa S.M., Longo F.M., and Barbeito L. Modulation of p75-dependent motor neuron death by a small non-peptidyl mimetic of the neurotrophin loop 1 domain. Eur. J. Neurosci. 24 (2006) 1575-1580
99. Peng G.S., Li G., Tzeng N.S., Chen P.S., Chuang D.M., Hsu Y.D., Yang S., and Hong J.S. Valproate pretreatment protects dopaminergic neurons from LPS-induced neurotoxicity in rat primary midbrain cultures: role of microglia. Brain Res. Mol. Brain Res. 134 (2005) 162-169
100. Pettmann B., and Henderson C.E. Neuronal cell death. Neuron 20 (1998) 633-647
101. Przedborski S. Neuroinflammation and Parkinson's disease. In: Koller W.C., and Melamed E. (Eds). Parkinson's Disease and Related Disorders (2007), Elsevier, New York 535-551
102. Przedborski S., and Goldman J.E. Pathogenic role of glial cells in Parkinson's disease. In: Hertz L. (Ed). Non-neuronal Cells of the Nervous System: Function and Dysfunction (2004), Elsevier, New York 967-982
103. Raoul C., Estevez A., Nishimune H., Cleveland D., deLapeyriere O., Henderson C., Haase G., and Pettmann B. Motoneuron death triggered by a specific pathway downstream of Fas. Potentiation by ALS-linked SOD1 mutations. Neuron 35 (2002) 1067-1083
104. Ridet J.L., Malhotra S.K., Privat A., and Gage F.H. Reactive astrocytes: cellular and molecular cues to biological function. Trends Neurosci. 20 (1997) 570-577
105. Rothe M., Xiong J., Shu H.B., Williamson K., Goddard A., and Goeddel D.V. I-TRAF is a novel TRAF-interacting protein that regulates TRAF-mediated signal transduction. Proc. Natl. Acad. Sci. U. S. A. 93 (1996) 8241-8246
106. Rowland L.P. Hereditary and acquired motor neuron diseases. In: Rowland L.P. (Ed). Merritt's Textbook of Neurology (1995), Williams & Wilkins, Philadelphia 742-749
107. Roy N., et al. The gene for neuronal apoptosis inhibitory protein is partially deleted in individuals with spinal muscular atrophy. Cell 80 (1995) 167-178
108. Sasabe J., Chiba T., Yamada M., Okamoto K., Nishimoto I., Matsuoka M., and Aiso S. d-Serine is a key determinant of glutamate toxicity in amyotrophic lateral sclerosis. EMBO J. 26 (2007) 4149-4159
109. Schiffer D., Cordera S., Cavalla P., and Migheli A. Reactive astrogliosis of the spinal cord in amyotrophic lateral sclerosis. J. Neurol. Sci. 139 (1996) 27-33
110. Schrank B., tz R., Gunnersen J.M., Ure J.M., Toyka K.V., Smith A.G., and Sendtner M. Inactivation of the survival motor neuron gene, a candidate gene for human spinal muscular atrophy, leads to massive cell death in early mouse embryos. Proc. Natl. Acad. Sci. U. S. A. 94 (1997) 9920-9925
111. Sekizawa T., Openshaw H., Ohbo K., Sugamura K., Itoyama Y., and Niland J.C. Cerebrospinal fluid interleukin 6 in amyotrophic lateral sclerosis: immunological parameter and comparison with inflammatory and non-inflammatory central nervous system diseases. J. Neurol. Sci. 154 (1998) 194-199
112. Solomon J.N., Lewis C.A.B., Ajami B., Corbel S.Y., Rossi F.M.V., and Krieger C. Origin and distribution of bone marrow-derived cells in the central nervous system in a mouse model of amyotrophic lateral sclerosis. Glia 53 (2006) 744-753
113. Strauss S., Otten U., Joggerst B., Pluss K., and Volk B. Increased levels of nerve growth-factor (Ngf) protein and messenger-RNA and reactive gliosis following kainic acid injection into the rat striatum. Neurosci. Lett. 168 (1994) 193-196
114. Strong M.J., Kesavapany S., and Pant H.C. The pathobiology of amyotrophic lateral sclerosis: A proteinopathy?. J. Neuropathol. Exp. Neurol. 64 (2005) 649-664
115. Tanaka K., Okada Y., Kanno T., Otomo A., Yanagisawa Y., Shouguchi-Miyata J., Suga E., Kohiki E., Onoe K., Osuga H., Aoki M., Hadano S., Itoyama Y., and Ikeda J.E. A dopamine receptor antagonist L-745,870 suppresses microglia activation in spinal cord and mitigates the progression in ALS model mice. Exp. Neurol. 211 (2008) 378-386
116. Trotti D., Danbolt N.C., and Volterra A. Glutamate transporters are oxidant-vulnerable: a molecular link between oxidative and excitotoxic neurodegeneration?. Trends Pharmacol. Sci. 19 (1998) 328-334
117. Tsai M.S., Chiu Y.T., Wang S.H., Hsieh-Li H.M., Lian W.C., and Li H. Abolishing Bax-dependent apoptosis shows beneficial effects on spinal muscular atrophy model mice. Mol. Ther. 13 (2006) 1149-1155
118. Turner B.J., and Talbot K. Transgenics, toxicity and therapeutics in rodent models of mutant SOD1-mediated familial ALS. Prog. Neurobiol. 85 (2008) 94-134
119. Urushitani M., Sik A., Sakurai T., Nukina N., Takahashi R., and Julien J.P. Chromogranin-mediated secretion of mutant superoxide dismutase proteins linked to amyotrophic lateral sclerosis. Nat. Neurosci. 9 (2006) 108-118
120. Van Damme P., Bogaert E., Dewil M., Hersmus N., Kiraly D., Scheveneels W., Bockx I., Braeken D., Verpoorten N., Verhoeven K., Timmerman V., Herijgers P., Callewaert G., Carmeliet P., Van Den B.L., and Robberecht W. Astrocytes regulate GluR2 expression in motor neurons and their vulnerability to excitotoxicity. Proc. Natl. Acad. Sci. U. S. A. 104 (2007) 14825-14830
121. NTR-dependent motor neuron apoptosis. J. Neurochem. 97 (2006) 687-696
122. von Bernhardi R., and Eugenin J. Microglial reactivity to beta-amyloid is modulated by astrocytes and proinflammatory factors. Brain Res. 1025 (2004) 186-193
123. Vukosavic S., Dubois-Dauphin M., Romero N., and Przedborski S. Bax and Bcl-2 interaction in a transgenic mouse model of familial amyotrophic lateral sclerosis. J. Neurochem. 73 (1999) 2460-2468
124. Wang J., Slunt H., Gonzales V., Fromholt D., Coonfield M., Copeland N.G., Jenkins N.A., and Borchelt D.R. Copper-binding-site-null SOD1 causes ALS in transgenic mice: aggregates of non-native SOD1 delineate a common feature. Hum. Mol. Genet. 12 (2003) 2753-2764
125. Wang J., Xu G., Slunt H.H., Gonzales V., Coonfield M., Fromholt D., Copeland N.G., Jenkins N.A., and Borchelt D.R. Coincident thresholds of mutant protein for paralytic disease and protein aggregation caused by restrictively expressed superoxide dismutase cDNA. Neurobiol. Dis. 20 (2005) 943-952
126. West M., Mhatre M., Ceballos A., Floyd R.A., Grammas P., Gabbita S.P., Hamdheydari L., Mai T., Mou S., Pye Q.N., Stewart C., West S., Williamson K.S., Zemlan F., and Hensley K. The arachidonic acid 5-lipoxygenase inhibitor nordihydroguaiaretic acid inhibits tumor necrosis factor alpha activation of microglia and extends survival of G93A-SOD1 transgenic mice. J. Neurochem. 91 (2004) 133-143
127. Weydt P., Yuen E.C., Ransom B.R., and Moller T. Increased cytotoxic potential of microglia from ALS-transgenic mice. Glia 48 (2004) 179-182
128. Wong P.C., Pardo C.A., Borchelt D.R., Lee M.K., Copeland N.G., Jenkins N.A., Sisodia S.S., Cleveland D.W., and Price D.L. An adverse property of a familial ALS-linked SOD1 mutation causes motor neuron disease characterized by vacuolar degeneration of mitochondria. Neuron 14 (1995) 1105-1116
129. Wu V.W., Nishiyama N., and Schwartz J.P. A culture model of reactive astrocytes: Increased nerve growth factor synthesis and reexpression of cytokine responsiveness. J. Neurochem. 71 (1998) 749-756
130. Wu D.C., Re D.B., Nagai M., Ischiropoulos H., and Przedborski S. The inflammatory NADPH oxidase enzyme modulates motor neuron degeneration in amyotrophic lateral sclerosis mice. Proc. Natl. Acad. Sci. U. S. A. 103 (2006) 12132-12137
131. Wyss-Coray T., and Mucke L. Inflammation in neurodegenerative disease-a double-edged sword. Neuron 35 (2002) 419-432
132. Yamanaka K., Boillee S., Roberts E.A., Garcia M.L., onis-Downes M., Mikse O.R., Cleveland D.W., and Goldstein L.S. Mutant SOD1 in cell types other than motor neurons and oligodendrocytes accelerates onset of disease in ALS mice. Proc. Natl. Acad. Sci. U. S. A. 105 (2008) 7594-7599
133. Yamanaka K., Chun S.J., Boillee S., Fujimori-Tonou N., Yamashita H., Gutmann D.H., Takahashi R., Misawa H., and Cleveland D.W. Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis. Nat. Neurosci. 11 (2008) 251-253
134. Yong J., Wan L., and Dreyfuss G. Why do cells need an assembly machine for RNA-protein complexes?. Trends Cell Biol. 14 (2004) 226-232
135. Yoshihara T., Ishigaki S., Yamamoto M., Liang Y., Niwa J., Takeuchi H., Doyu M., and Sobue G. Differential expression of inflammation- and apoptosis-related genes in spinal cords of a mutant SOD1 transgenic mouse model of familial amyotrophic lateral sclerosis. J. Neurochem. 80 (2002) 158-167
136. Zhang B., West E.J., Van K.C., Gurkoff G.G., Zhou J., Zhang X.M., Kozikowski A.P., and Lyeth B.G. HDAC inhibitor increases histone H3 acetylation and reduces microglia inflammatory response following traumatic brain injury in rats. Brain Res. 1226 (2008) 181-191
137. Zhao W., Xie W., Le W., Beers D.R., He Y., Henkel J.S., Simpson E.P., Yen A.A., Xiao Q., and Appel S.H. Activated microglia initiate motor neuron injury by a nitric oxide and glutamate-mediated mechanism. J. Neuropathol. Exp. Neurol. 63 (2004) 964-977
138. Zhong Z., Deane R., Ali Z., Parisi M., Shapovalov Y., O'Banion M.K., Stojanovic K., Sagare A., Boillee S., Cleveland D.W., and Zlokovic B.V. ALS-causing SOD1 mutants generate vascular changes prior to motor neuron degeneration. Nat. Neurosci. 11 (2008) 420-422
139. Zhu S., Stavrovskaya I., Drozda M., Kim B., Ona V., Li M., Sarang S., Liu A., Hartley D., Wu D., Gullans S., Ferrante R., Przedborski S., Kristal B., and Friedlander R. Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice. Nature 417 (2002) 74-78