Journal of Neuroimmunology
Volume 229, Issue 1 , Pages 157-168 , 15 December 2010

Increased intramuscular nerve branching and inhibition of programmed cell death of chick embryo motoneurons by immunoglobulins from patients with motoneuron disease

  • Sara Hernández

      Affiliations

    • Universitat de Lleida, Facultat de Medicina, Departament de Medicina Experimental, and IRBLLEIDA, Montserrat Roig 2, Lleida, Catalonia, Spain
    • ,
  • Laura Texidó

      Affiliations

    • Universitat de Barcelona, Departament de Patologia i Terapèutica Experimental, and IDIBELL, Spain
    • ,
  • Jordi Calderó

      Affiliations

    • Universitat de Lleida, Facultat de Medicina, Departament de Medicina Experimental, and IRBLLEIDA, Montserrat Roig 2, Lleida, Catalonia, Spain
    • ,
  • Dolors Ciutat

      Affiliations

    • Universitat de Lleida, Facultat de Medicina, Departament de Medicina Experimental, and IRBLLEIDA, Montserrat Roig 2, Lleida, Catalonia, Spain
    • ,
  • Lídia Piedrafita

      Affiliations

    • Universitat de Lleida, Facultat de Medicina, Departament de Medicina Experimental, and IRBLLEIDA, Montserrat Roig 2, Lleida, Catalonia, Spain
    • ,
  • Anna Casanovas

      Affiliations

    • Universitat de Lleida, Facultat de Medicina, Departament de Medicina Experimental, and IRBLLEIDA, Montserrat Roig 2, Lleida, Catalonia, Spain
    • ,
  • Joan Blasi

      Affiliations

    • Universitat de Barcelona, Departament de Patologia i Terapèutica Experimental, and IDIBELL, Spain
    • ,
  • Carles Solsona

      Affiliations

    • Universitat de Barcelona, Departament de Patologia i Terapèutica Experimental, and IDIBELL, Spain
    • ,
  • Mònica Povedano

      Affiliations

    • Hospital de Bellvitge, Servei de Neurologia, C. Feixa Llarga s/n, Hospitalet de Llobregat, Catalonia, Spain
    • ,
  • Ricardo Rojas

      Affiliations

    • Hospital de la Santa Creu i Sant Pau, Departament de Neurologia, C. Sant Antoni Maria Claret 167, Barcelona, Catalonia, Spain
    • ,
  • Isabel Illa

      Affiliations

    • Hospital de la Santa Creu i Sant Pau, Departament de Neurologia, C. Sant Antoni Maria Claret 167, Barcelona, Catalonia, Spain
    • ,
  • James Caress

      Affiliations

    • Department of Neurology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
    • ALS Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
    • ,
  • David Prevette

      Affiliations

    • Department of Neurobiology and Anatomy and Neuroscience Program, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
    • ,
  • Ronald W. Oppenheim

      Affiliations

    • Department of Neurobiology and Anatomy and Neuroscience Program, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
    • ALS Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
    • ,
  • Carol Milligan

      Affiliations

    • Department of Neurobiology and Anatomy and Neuroscience Program, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
    • ALS Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
    • ,
  • Josep E. Esquerda

      Affiliations

    • Universitat de Lleida, Facultat de Medicina, Departament de Medicina Experimental, and IRBLLEIDA, Montserrat Roig 2, Lleida, Catalonia, Spain
    • Corresponding Author InformationCorresponding author. Unitat de Neurobiologia Cel·lular, Departament de Medicina Experimental, Facultat de Medicina, Universitat de Lleida, C. Montserrat Roig 2, 25008 Lleida, Catalonia, Spain. Tel.: +34 973 702427; fax: +34 973 702426.

Received 26 March 2010 ,Revised 27 July 2010 ,Accepted 28 July 2010.

References 

  1. Alexianu ME, Mohamed AH, Smith RG, Colom LV, Appel SH. Apoptotic cell death of a hybrid motoneuron cell line induced by immunoglobulins from patients with amyotrophic lateral sclerosis. J. Neurochem. 1994;63:2365–2368
  2. Alexianu ME, Kozovska M, Appel SH. Immune reactivity in a mouse model of familial ALS correlates with disease progression. Neurology. 2001;57:1282–1289
  3. Andjus PR, Khiroug L, Nistri A, Cherubini E. ALS IgGs suppress [Ca2+]i rise through P/Q-type calcium channels in central neurones in culture. Neuroreport. 1996;7:1914–1916
  4. Andjus PR, Stevic-Marinkovic Z, Cherubini E. Immunoglobulins from motoneurone disease patients enhance glutamate release from rat hippocampal neurones in culture. J. Physiol. 1997;504:103–112
  5. Apostolski S, Nikolic J, Bugarski-Prokopljevic C, Miletic V, Pavlovic S, Filipovic S. Serum and CSF immunological findings in ALS. Acta Neurol. Scand. 1991;83:96–98
  6. Appel SH, Engelhardt JI, Garcia J, Stefani E. 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. USA. 1991;88:647–651
  7. Arsac C, Raymond C, Martin-Moutot N, Dargent B, Couraud F, Pouget J, et al. Immunoassays fail to detect antibodies against neuronal calcium channels in amyotrophic lateral sclerosis serum. Ann. Neurol. 1996;40:695–700
  8. Barber SC, Shaw PJ. Molecular mechanisms of motor degeneration in amyotrophic lateral sclerosis. In:  Eisen AA,  Shaw PJ editor. Handbook of Clinical Neurology. Motor Neuron Disorders and Related Diseases. Vol. 82 (3rd series):Amsterdam: Elsevier; 2007;p. 57–87
  9. Bottenstein JE, Skaper SD, Varon SS, Sato GH. Selective survival of neurons from chick embryo sensory ganglionic dissociates utilizing serum-free supplemented medium. Exp. Cell Res. 1980;125:183–190
  10. Brooks BR. El Escorial World Federation of Neurology criteria for the diagnosis of amyotrophic lateral sclerosis. Subcommittee on Motor Neuron Diseases/Amyotrophic Lateral Sclerosis of the World Federation of Neurology Research Group on Neuromuscular Diseases and the El Escorial “Clinical limits of amyotrophic lateral sclerosis” workshop contributors. J. Neurol. Sci. 1994;124:96–107Suppl
  11. Bruijn LI, Miller TM, Cleveland DW. Unraveling the mechanisms involved in motor neuron degeneration in ALS. Annu. Rev. Neurosci. 2004;27:723–749
  12. Calderó J, Ciutat D, Lladó J, Castán E, Oppenheim RW, Esquerda JE. Effects of excitatory amino acids on neuromuscular development in the chick embryo. J. Comp. Neurol. 1997;387:73–95
  13. Calderó J, Prevette D, Mei X, Oakley RA, Li L, Milligan C, et al. Peripheral target regulation of the development and survival of spinal sensory and motor neurons in the chick embryo. J. Neurosci. 1998;18:356–370
  14. Calderó J, Tarabal O, Casanovas A, Ciutat D, Casas C, Lladó J, et al. Excitotoxic motoneuron disease in chick embryo evolves with autophagic neurodegeneration and deregulation of neuromuscular innervation. J. Neurosci. Res. 2007;85:2726–2740
  15. Carter JR, Mynlieff M. Amyotrophic lateral sclerosis patient IgG alters voltage dependence of Ca2+ channels in dissociated rat motoneurons. Neurosci. Lett. 2003;353:221–225
  16. Clarke PGH, Oppenheim RW. Neuron death in vertebrate development: in vivo methods. In:  Schwartz LM,  Osborne BA editor. Methods in cell biology: cell death. Vol. 46:New York: Academic; 1995;p. 277–321
  17. Cleveland DW, Rothstein JD. From Charcot to Lou Gehrig: deciphering selective motor neuron death in ALS. Nat. Rev. Neurosci. 2001;2:806–819
  18. Colom LV, Alexianu ME, Mosier DR, Smith RG, Appel SH. Amyotrophic lateral sclerosis immunoglobulins increase intracellular calcium in a motoneuron cell line. Exp. Neurol. 1997;146:354–360
  19. Couratier P, Yi FH, Preud'Homme JL, Clavelou P, Whit A, Sindou P, et al. Serum autoantibodies to neuroilament proteins in sporadic amyotrophic lateral sclerosis. J. Neurol. Sci. 1998;154:137–145
  20. De Winter F, Vo T, Stam FJ, Wisman LA, Bär PR, Niclou SP, et al. The expression of the chemorepellent Semaphorin 3A is selectively induced in terminal Schwann cells of a subset of neuromuscular synapses that display limited anatomical plasticity and enhanced vulnerability in motor neuron disease. Mol. Cell. Neurosci. 2006;32:102–117
  21. Delbono O, García J, Appel SH, Stefani E. Calcium current and charge movement of mammalian muscle: action of amyotrophic lateral sclerosis immunoglobulins. J. Physiol. 1991;444:723–742
  22. Demestre M, Pullen A, Orrell RW, Orth M. ALS-IgG-induced selective motor neurone apoptosis in rat mixed primary spinal cord cultures. J. Neurochem. 2005;94:268–275
  23. Drachman DB, Fishman PS, Rothstein JD, Motomura M, Lang B, Vicent A, et al. Amyotrophic lateral sclerosis. An autoimmune disease?. In:  Serratrice G,  Munsat T editor. Pathogenesis and therapy of amyotrophic lateral sclerosis. Advances in Neurology. Vol. 68:Philalelphia: Lippincot-raven Piblishers; 1995;p. 59–65
  24. Duplan L, Bernard N, Casseron W, Dudley K, Thouvenot E, Honnorat J, et al. Collapsin response mediator protein 4a (CRMP4a) is upregulated in motoneurons of mutant SOD1 mice and can trigger motoneuron axonal degeneration and cell death. J. Neurosci. 2010;30:785–796
  25. Engelhardt JI, Siklos L, Appel SH. Altered calcium homeostasis and ultrastructure in motoneurons of mice caused by passively transferred anti-motoneuronal IgG. J. Neuropathol. Exp. Neurol. 1997;56:21–39
  26. Fratantoni SA, Weisz G, Pardal AM, Reisin RC, Uchitel OD. Amyotrophic lateral sclerosis IgG-treated neuromuscular junctions develop sensitivity to L-type calcium channel blocker. Muscle Nerve. 2000;23:543–550
  27. Frey D, Schneider C, Xu L, Borg J, Spooren W, Caroni P. Early and selective loss of neuromuscular synapse subtypes with low sprouting competence in motoneuron diseases. J. Neurosci. 2000;20:2534–???
  28. Grassi C, Martire M, Altobelli D, Azzena GB, Preziosi P. Characterization of Ca(2+)-channels responsible for K(+)-evoked [(3)H]noradrenaline release from rat brain cortex synaptosomes and their response to amyotrophic lateral sclerosis IgGs. Exp. Neurol. 1999;159:520–527
  29. Guiloff RJ. Functional scales in ALS: cons. Amyotroph. Lateral Scler. Other Mot. Neuron Disord. 2002;3(Suppl 1):S11–2
  30. Guiloff RJ, McGregor B, Thompson E, Blackwood W, Paul E. Motor neurone disease with elevated cerebrospinal fluid protein. J. Neurol. Neurosurg. Psychiatry. 1980;43:390–396
  31. Gurney ME, Pu H, Chiu AY, Dal Canto MC, Polchow CY, Alexander DD, et al. Motor neuron degeneration in mice that express a human Cu, Zn superoxide dismutase mutation. Science. 1994;1264:1772–1775
  32. Henkel JS, Engelhardt JI, Siklós L, Simpson EP, Kim SH, Pan T, et al. Presence of dendritic cells, MCP-1, and activated microglia/macrophages in amyotrophic lateral sclerosis spinal cord tissue. Ann. Neurol. 2004;55:221–235
  33. Houenou LJ, Li L, Lo AC, Yan Q, Oppenheim RW. Naturally occurring and axotomy-induced motoneuron death and its prevention by neurotrophic agents: a comparison between chick and mouse. Prog. Brain Res. 1994;102:217–226
  34. Huber AB, Kania A, Tran TS, Gu C, De Marco Garcia N, Lieberam I, et al. Distinct roles for secreted semaphorin signaling in spinal motor axon guidance. Neuron. 2005;48:949–964
  35. Johnson EM, Koike T, Franklin J. A “calcium set-point hypothesis” of neuronal dependence on neurotrophic factor. Exp. Neurol. 1992;115:163–166
  36. Jokic N, Gonzalez de Aguilar JL, Pradat PF, Dupuis L, Echaniz-Laguna A, Muller A, et al. Nogo expression in muscle correlates with amyotrophic lateral sclerosis severity. Ann. Neurol. 2005;57:553–556
  37. Jokic N, Gonzalez de Aguilar JL, Dimou L, Lin S, Fergani A, Ruegg MA, et al. The neurite outgrowth inhibitor Nogo-A promotes denervation in an amyotrophic lateral sclerosis model. EMBO Rep. 2006;7:1162–1167
  38. Kawamata T, Akiyama H, Yamada T, McGeer PL. Immunologic reactions in amyotrophic lateral sclerosis brain and spinal cord tissue. Am. J. Pathol. 1992;140:691–707
  39. Keegan BM, Pittock SJ, Lennon VA. Autoimmune myelopathy associated with collapsin response-mediator protein-5 immunoglobulin G. Ann. Neurol. 2008;63:531–534
  40. Kimura F, Smith RG, Delbono O, Nyormoi O, Schneider T, Nastainczyk W, et al. Amyotrophic lateral sclerosis patient antibodies label Ca2+ channel alpha 1 subunit. Ann. Neurol. 1994;35:164–171
  41. Knudsen A, Bredholt G, Storstein A, Oltedal L, Davanger S, Krossnes B, et al. Antibodies to CRMP3-4 associated with limbic encephalitis and thymoma. Clin. Exp. Immunol. 2007;149:16–22
  42. Kolodkin AL. Semaphorins: mediators of repulsive growth cone guidance. Trends Cell Biol. 1996;6:15–22
  43. Kriz J, Nguyen MD, Julien JP. Minocycline slows disease progression in a mouse model of amyotrophic lateral sclerosis. Neurobiol. Dis. 2002;10:268–278
  44. Leonardi A, Abbruzzese G, Arata L, Cocito L, Vische M. Cerebrospinal fluid (CSF) findings in amyotrophic lateral sclerosis. J. Neurol. 1984;231:75–238
  45. Li B, Liu XY, Li Z, Bu H, Sun MM, Guo YS, et al. Effect of ALS IgG on motor neurons in organotypic spinal cord cultures. Can. J. Neurol. Sci. 2008;35:220–225
  46. Llinás R, Sugimori M, Cherksey BD, Smith RG, Delbono O, Stefani E, et al. IgG from amyotrophic lateral sclerosis patients increases current through P-type calcium channels in mammalian cerebellar Purkinje cells and in isolated channel protein in lipid bilayer. Proc. Natl. Acad. Sci. U.S.A. 1993;90:11743–11747
  47. Magnelli V, Sawada T, Delbono O, Smith RG, Appel SH, Stefani E. The action of amyotrophic lateral sclerosis immunoglobulins on mammalian single skeletal muscle Ca2+ channels. J. Physiol. 1993;461:103–118
  48. Martí-Fabregas J, Soler R, Esquerda JE, Grau JM, Pradas J, Illa I. Clinical status of motoneuron disease does not correlate with serum neurotoxicity on cultured neurons. Acta Neurol. Scand. 1992;85:219–223
  49. Millecamps S, Nicolle D, Ceballos-Picot I, Mallet J, Barkats M. Synaptic sprouting increases the uptake capacities of motoneurons in amyotrophic lateral sclerosis mice. Proc. Natl. Acad. Sci. U.S.A. 2001;98:7582–7587
  50. Mosier DR, Baldelli P, Delbono O, Smith RG, Alexianu ME, Appel SH, et al. Amyotrophic lateral sclerosis immunoglobulins increase Ca2+ currents in a motoneuron cell line. Ann. Neurol. 1995;37:102–109
  51. Murray B, Mitsumoto H. Amyotrophic lateral sclerosis. In:  Katirji B,  Kaminski HJ,  Preston DC,  Ruff RL,  Shapiro BE editor. Neuromuscular Disorders in Clinical Practice. Boston: Butterworth-Heinemann; 2002;p. 417–444
  52. Niebroj-Dobosz I, Janik P, Kwieciński H. Serum IgM anti-GM1 ganglioside antibodies in lower motor neuron syndromes. Eur. J. Neurol. 2004;l1:13–16
  53. Offen D, Halevi S, Orion D, Mosberg R, Stern-Goldberg H, Melamed E, et al. Antibodies from ALS patients inhibit dopamine release mediated by L-type calcium channels. Neurology. 1998;51:1100–1103
  54. Oppenheim RW. Muscle activity and motor neuron death in the spinal cord of the chick embryo. In: Selective Neuronal Death, Ciba Foundation Symposium. nº 126:Chichester: John Wiley & Sons; 1987;p. 96–112
  55. Oppenheim RW. Cell death during development of the nervous system. Annu. Rev. Neurosci. 1991;14:453–501
  56. Oppenheim RW, Bursztajn S, Prevette D. Cell death of motoneurons in the chick embryo spinal cord: acetylcholine receptors and synaptogenesis in skeletal muscle following the reduction of motoneuron death by neuromuscular blockade. Development. 1989;107:331–341
  57. Oppenheim RW, Houenou LJ, Johnson JE, Lin LF, Li L, Lo AC, et al. Developing motor neurons rescued from programmed and axotomy-induced cell death by GDNF. Nature. 1995;373:344–346
  58. Oppenheim RW, Calderó J, Ciutat D, Esquerda JE, Ayala V, Prevette D, et al. Rescue of developing spinal motoneurons from programmed cell death by the GABA(A) agonist muscimol acts by blockade of neuromuscular activity and increased intramuscular nerve branching. Mol. Cell. Neurosci. 2003;22:331–343
  59. Pagani MR, Reisin RC, Uchitel OD. Calcium signaling pathways mediating synaptic potentiation triggered by amyotrophic lateral sclerosis IgG in motor nerve terminals. J. Neurosci. 2006;26:2661–2672
  60. Pasinelli P, Brown RH. Molecular biology of amyotrophic lateral sclerosis: insights from genetics. Nat. Rev. Neurosci. 2006;7:710–723
  61. Pestronk A, Adams RN, Cornblath D, Kuncl RW, Drachman DB, Clawson L. Patterns of serum IgM antibodies to GM1 and GD1a gangliosides in amyotrophic lateral sclerosis. Ann. Neurol. 1989;25:98–102
  62. Pradat PF, Bruneteau G, Gonzalez de Aguilar JL, Dupuis L, Jokic N, Salachas F, et al. Muscle Nogo-A expression is a prognostic marker in lower motor neuron syndromes. Ann. Neurol. 2007;62:15–20
  63. Pun S, Santos AF, Saxena S, Xu L, Caroni P. Selective vulnerability and pruning of phasic motoneuron axons in motoneuron disease alleviated by CNTF. Nat. Neurosci. 2006;9:408–419
  64. Raper JA, Kapfhammer JP. The enrichment of a neuronal growth cone collapsing activity from embryonic chick brain. Neuron. 1990;4:21–29
  65. Rosen DR, Siddique T, Patterson D, Figlewicz DA, Sapp P, Hentati A, et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature. 1993;362:59–62
  66. Saleh IA, Zesiewicz T, Xie Y, Sullivan KL, Miller AM, Kuzmin-Nichols N, et al. Evaluation of humoral immune response in adaptive immunity in ALS patients during disease progression. J. Neuroimmunol. 2009;215:96–101
  67. Schaefer AM, Sanes JR, Lichtman JW. A compensatory subpopulation of motor neurons in a mouse model of amyotrophic lateral sclerosis. J. Comp. Neurol. 2005;490:209–219
  68. Sengun IS, Appel SH. Serum anti-Fas antibody levels in amyotrophic lateral sclerosis. J. Neuroimmunol. 2003;142:137–140
  69. Shaw PJ. Molecular and cellular pathways of neurodegeneration in motor neurone disease. J. Neurol. Neurosurg. Psychiatry. 2005;76:1046–1057
  70. Smith RG, Hamilton S, Hofmann F, Schneider T, Nastainczyk W, Birnbaumer L, et al. Serum antibodies to L-type calcium channels in patients with amyotrophic lateral sclerosis. N. Engl. J. Med. 1992;327:1721–1728
  71. Smith RG, Alexianu ME, Crawford G, Nyormoi O, Stefani E, Appel SH. Cytotoxicity of immunoglobulins from amyotrophic lateral sclerosis patients on a hybrid motoneuron cell line. Proc. Natl. Acad. Sci. U.S.A. 1994;91:3393–3397
  72. Soler RM, Egea J, Mintenig GM, Sanz-Rodriguez C, Iglesias M, Comella JX. Calmodulin is involved in membrane depolarization-mediated survival of motoneurons by phosphatidylinositol-3 kinase- and MAPK-independent pathways. J. Neurosci. 1998;18:1230–1239
  73. Stålberg E, Schwartz MS, Trontelj JV. Single fibre electromyography in various processes affecting the anterior horn cell. J. Neurol. Sci. 1975;24:403–415
  74. Stevens A, Weller M, Wiethölter H. A characteristic ganglioside antibody pattern in the CSF of patients with amyotrophic lateral sclerosis. J. Neurol. Neurosurg. Psychiatry. 1993;56:361–364
  75. Thomas MM, Dunn SM. Amyotrophic lateral sclerosis immunoglobulins are ineffective in altering calcium influx through presynaptic voltage-sensitive calcium channels. Neurol. Res. 1997;119:129–134
  76. Tikka TM, Vartiainen NE, Goldsteins G, Oja SS, Andersen PM, Marklund SL, et al. Minocycline prevents neurotoxicity induced by cerebrospinal fluid from patients with motor neurone disease. Brain. 2002;125:722–731
  77. Troost D, van den Oord JJ, de Jong JM, Swaab DF. Lymphocytic infiltration in the spinal cord of patients with amyotrophic lateral sclerosis. Clin. Neuropath. 1989;8:289–294
  78. Uchitel OD, Appel SH, Crawford F, Sczcupak L. Immunoglobulins from amyotrophic lateral sclerosis patients enhance spontaneous transmitter release from motor-nerve terminals. Proc. Natl. Acad. Sci. U.S.A. 1988;85:7371–7374
  79. Westarp ME, Schreiber H, Westarp MP, Westphal KP, Mauch E, Kornhuber HH. Cerebral magnetic resonance imaging pathology and cerebro-spinal fluid protein in sporadic amyotrophic lateral sclerosis (sALS). Clin. Neuropathol. 1995;14:228–232
  80. Yi FH, Lautrette C, Vermot-Desroches C, Bordessoule D, Couratier P, Wijdenes J, et al. In vitro induction of neuronal apoptosis by anti-Fas antibody-containing sera from amyotrophic lateral sclerosis patients. J. Neuroimmunol. 2000;109:211–220
  81. Yoshino H, Miyatani N, Saito M, Ariga T, Lugaresi A, Latov N, et al. Isolated bovine spinal motoneurons have specific ganglioside antigens recognized by sera from patients with motor neuron disease and motor neuropathy. J. Neurochem. 1992;59:1684–1691
  82. Younger DS, Rowland LP, Latov N, Sherman W, Pesce M, Lange DJ, et al Motor neuron disease and amyotrophic lateral sclerosis: relation of high CSF protein content to paraproteinemia and clinical syndromes. Neurology. 1990;40:595–599
  83. Yu Z, Kryzer TJ, Griesmann GE, Kim K, Benarroch EE, Lennon VA. CRMP-5 neuronal autoantibody: marker of lung cancer and thymoma-related autoimmunity. Ann. Neurol. 2001;49:146–154
  84. Zhang R, Gascon R, Miller RG, Gelinas DF, Mass J, Hadlock K, et al. Evidence for systemic immune system alterations in sporadic amyotrophic lateral sclerosis (sALS). J. Neuroimmunol. 2005;159:215–224
  85. Zhu S, Stavrovskaya IG, Drozda M, Kim BY, Ona V, Li M, et al. Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice. Nature. 2002;417:74–78

PII: S0165-5728(10)00341-3

doi: 10.1016/j.jneuroim.2010.07.028

Journal of Neuroimmunology
Volume 229, Issue 1 , Pages 157-168 , 15 December 2010

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