Oxidative Stress Plays a Role in the Pathogenesis of Familial and Sporadic Amyotrophic Lateral Sclerosis

  • Catherine Bergeron
  • Connie Petrunka
  • Luitgard Weyer
Part of the GWUMC Department of Biochemistry and Molecular Biology Annual Spring Symposia book series (GWUN)

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the selective death of upper and lower motorneurons. The disease affects 0.6–2.6:100,000 individuals1, with a mean age at onset of approximately 55 and a duration of two to three years on average2. Motorneuron death results in muscle weakness and paralysis with eventual ventilatory failure and death.

Keywords

Superoxide Dismutase Amyotrophic Lateral Sclerosis Motor Neuron Disease Sporadic Amyotrophic Lateral Sclerosis Familial Amyotrophic Lateral Sclerosis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    C. N. Martyn, Epidemiology, in: “Motor neuron disease”, AC Williams ed., Chapman & Hall Medical, London (1994).Google Scholar
  2. 2.
    R. Tandan, Clinical features and differential diagnosis of classical motor neuron disease, in: “Motorneuron disease”, AC Williams ed., Chapman & Hall Medical, London (1994).Google Scholar
  3. 3.
    A. J. Windebank, and D. B. Williams, Motor Neuron Disease, in: “Peripheral Neuropathy”, Peter James Dyck and PK Thomas ed., W.B. Saunders Company, Philadelphia (1993).Google Scholar
  4. 4.
    B. Halliwell, Reactive oxygen species and the central nervous system, J Neuropathol. 59:1609 (1992).Google Scholar
  5. 5.
    K. E. Muse, T. D. Oberley, J.M. Sempf, and L. W. Oberley, Immunolocalization of antioxidant enzymes in adult hamster kidney, Histochem J. 26:734 (1994).PubMedCrossRefGoogle Scholar
  6. 6.
    T. D. Oberley, L. W. Oberley, A. F. Slattery, L. J. Lauchner, and J. H. Elwell, Immunohistochemical localization of antioxidant enzymes in adult Syrian hamster tissues and during kidney development, Am J Pathol 137:199 (1990).PubMedGoogle Scholar
  7. 7.
    P. Zhang, P. Damier, E. Hirsh, Y. Agid, I. Ceballos-Picot, P. Sinet, A. Nicole, M. Laurent, and F. Javoy-Agid, Preferential expression of Superoxide dismutase messenger RNA in melanized neurons of human mesencephalon, Neurosci. 55:167 (1993).CrossRefGoogle Scholar
  8. 8.
    Ceballos, F. Javoy-Agid, A. Delacourte, A. Defossez, M. Lafon, E. Hirsch, A. Nicole, P. Sinet, and Y. Agid, Neuronal localization of copper-zinc Superoxide dismutase protein and mRNA within the human hippocampus from control and Alzheimer’s disease brains, Free Rod Res Comm. 12-13:571 (1991).CrossRefGoogle Scholar
  9. 9.
    S. P. Raps, J. C. Lai, L. Hertz, and A. J. Cooper, Glutathione is present in high concentrations in cultured astrocytes but not in cultured neurons, Brain Res. 493:398 (1989).PubMedCrossRefGoogle Scholar
  10. 10.
    A. Slivka, C. Mytilineou, and G. Cohen, Histochemical evaluation of glutathione in brain, Brain Res. 409:275 (1987).PubMedCrossRefGoogle Scholar
  11. 11.
    T. K. Makar, M. Nedergaard, A. Preuss, A. Gelbard, A. Perumal, and A.J. Cooper, Vitamin E, ascorbate, glutathione, glutathione disulfide, and enzymes of glutathione metabolism in cultures of chick astrocytes and neurons: evidence that astrocytes play an important role in antioxidative processes in the brain, J Neurochem. 62:45 (1994).PubMedCrossRefGoogle Scholar
  12. 12.
    P. Damier, E. Hirsch, P. Zhang, Y. Agid, and F. Javoy-Agid, Glutathione peroxidase, glial cells and Parkinson’s disease, Neurosci. 52:1 (1993).CrossRefGoogle Scholar
  13. 13.
    P. Zhang, P. Anglade, E. Hirsch, F. Javoy-Agid, and Y. Agid, Distribution of manganese-dependent Superoxide dismutase in the human brain, Neurosci. 61:317 (1994).CrossRefGoogle Scholar
  14. 14.
    D. R. Rosen, T. Siddique, D. Patterson, D. A. Figlewicz, P. Sapp, A. Hentati, D. Donaldson, J. Goto, J. P. O’Regan, H.-X. Deng, Z. Rahmani, A. Krizus, D. McKenna-Yasek, A. Cayabyab, S. M. Gaston, R. Berger, R. E. Tanzi, J. J. Halperin, B. Herzfeldt, R. Van den Bergh, W.-Y. Hung, T. Bird, G. Deng, D. W. Mulder, C. Smyth, N. G. Laing, E. Soriano, M. A. Pericak-Vance, J. Haines, G. A. Rouleau, J. S. Gusella, R. S. Horvitz, and R. H. Brown Jr, Mutations in Cu/Zn Superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis, Nature. 362:59 (1993).PubMedCrossRefGoogle Scholar
  15. 15.
    A. Elshafey, G. W. Lanyon, and M. J. Connor, Identification of a new missense point mutation in exon 4 of the Cu/Zn Superoxide dismutase (SOD-1) gene in a family with amyotrophic lateral sclerosis, Hum Mol Genet. 3:363 (1994).PubMedCrossRefGoogle Scholar
  16. 16.
    M. Ogasawara, Y. Matsubara, K. Narisawa, M. Aoki, S. Nakamura, and K. Abe, Mild ALS in Japan associated with novel SOD mutation, Nature Genet. 5:323 (1993).PubMedCrossRefGoogle Scholar
  17. 17.
    R. Nakano, S. Sato, T. Inuzuka, K. Sakimura, M. Mishina, H. Takahashi, F. Ikuta, Y. Honma, J. Fujii, N. Taniguchi, and S. Tsuji, A novel mutation in Cu/Zn Superoxide dismutase gene in Japanese familial amyotrophic lateral sclerosis, Biochem Biophys Res Comm. 200:695 (1994).PubMedCrossRefGoogle Scholar
  18. 18.
    J. Kawamata, H. Hasegawa, S. Shimohama, J. Kimura, S. Tanaka, and K. Ueda, Leu106-Val (CTC-GTC) mutation of Superoxide dismutase-1 gene in patient with familial amyotrophic lateral sclerosis in Japan, Lancet. 343:1501 (1994).PubMedCrossRefGoogle Scholar
  19. 19.
    A. Pramatarova, J. Goto, E. Nanma, K. Nakashima, K. Takahashi, A. Takaji, I. Kanazawa, D. A. Figlewicz, and G. A. Rouleau, A two basepair deletion in the SOD 1 gene causes familial amyotrophic lateral sclerosis, Hum Mol Genet. 3:2016 (1994).Google Scholar
  20. 20.
    H.-X. Deng, A. Hentati, J. A. Tainer, Z. Iqbal, A. Cayabyab, W.-Y. Hung, E. D. Getzoff, P. Hu, B. Herzfeldt, R. P. Roos, C. Warner, G. Deng, E. Soriano, C. Smyth, H. E. Parge, A. Ahmed, A. D. Roses, R. A. Hallewell, M. A. Pericak-Vance, and T. Siddique, Amyotrophic Lateral Sclerosis and structural defects in Cu,Zn Superoxide dismutase, Science. 261:1047 (1993).PubMedCrossRefGoogle Scholar
  21. 21.
    L. P. Rowland, Amyotrophic lateral sclerosis: human challenge for neuroscience, Proc Natl Acad Sci USA. 92:1251 (1995).PubMedCrossRefGoogle Scholar
  22. 22.
    R. H. J. Brown, Amyotrophic lateral sclerosis: Recent insights from genetics and transgenic mice, Cell 80:688 (1995).Google Scholar
  23. 23.
    M. E. Gurney, H. Pu, A. Y. Chiu, M. C. Dal Canto, C. Y. Polchow, D. D. Alexander, J. Caliendo, A. Hentati, Y. W. Kwon, H.-X. Deng, W. Chen, P. Zhai, R. L. Sufit, and T. Siddique, Motorneuron degeneration in mice that express a human Cu,Zn Superoxide dismutase mutation, Science. 264:1772 (1994).PubMedCrossRefGoogle Scholar
  24. 24.
    J. Fujii, T. Myint, H. G. Seo, Y. Kayanoki, Y. Ikeda, and N. Taniguchi, Characterization of wild-type and amyotrophic lateral sclerosis-related mutant Cu,Zn-superoxide dismutases overproduced in baculovirus-infected cells, J Neuropathol. 64:1456 (1995).Google Scholar
  25. 25.
    M. E. Ripps, G. W. Huntly, P. R. Hof, J. H. Morrison, and J. Gordon, Transgenic mice expressing an altered murine Superoxide dimutase gene provide an animal model of amyotrophic lateral sclerosis, Proc NatlAcad Sci USA. 92:689 (1995).CrossRefGoogle Scholar
  26. 26.
    D. R. Borchelt, M. K. Lee, H. S. Slunt, M. Guarnieri, Z.-S. Xu, P. C. Wong, R. H. J. Brown, D. L. Price, S. S. Sisodia, and D. W. Cleveland, Superoxide dismutase 1 mutations linked to familial amyotrophic lateral sclerosis possesses significant activity, Proc Natl Acad Sci USA. 91:8292 (1994).PubMedCrossRefGoogle Scholar
  27. 27.
    J. S. Beekman, M. Carson, C. D. Smith, and W. H. Koppenol, ALS, SOD and peroxynitrite, Nature. 364:584 (1993).CrossRefGoogle Scholar
  28. 28.
    C. Bergeron, S. Muntasser, M. J. Somerville, L. Weyer, and M. E. Percy, Copper/Zinc Superoxide dismutase mRNA levels are increased in sporadic amyotrophic lateral sclerosis motorneurons, Brain Res. 659:272 (1994).PubMedCrossRefGoogle Scholar
  29. 29.
    M. A. Haas, J. Iqbal, L. B. Clerch, L. Frank, and D. Massaro, Rat lung Cu,Zn Superoxide dismutase. Isolation and sequence of a full-length cDNA and studies of enzyme induction, J. Clin Invest. 83:1241 (1989).CrossRefGoogle Scholar
  30. 30.
    L. Jornot, and A. Junod, Response of human endothelial cell antioxidant enzymes to hyperoxia, Am J Respir Cell Mol Biol. 6:107 (1992).PubMedCrossRefGoogle Scholar
  31. 31.
    X.-J. Kong, Cu, Zn Superoxide dismutase in vascular cells: changes during cell cycling and exposure to hyperoxia, Am J Physiol 264:1365 (1993).Google Scholar
  32. 32.
    T. Matsuyama, H. Michishita, H. Nakamura, M. Tsuchiyama, S. Shimizu, K. Watanabe, and M. Sugita, Induction of Copper-Zinc Superoxide dismutase in gerbil hippocampus after ischemia, J Cereb Blood Flow Metab. 13:135 (1993).PubMedCrossRefGoogle Scholar
  33. 33.
    P. Ince, P. Shaw, J. Candy, D. Mantle, L. Tandon, W. Ehmann, and W. Markesbery, Iron, selenium and glutathione peroxidase activity are elevated in sporadic motor neuron disease, Neurosci Lett. 182:87 (1994).PubMedCrossRefGoogle Scholar
  34. 34.
    E. R. Stadtman, Protein oxidation and aging, Science. 257:1220 (1992).PubMedCrossRefGoogle Scholar
  35. 35.
    A. C. Bowling, J. B. Schulz, R. H. Brown, and M. F. Beal, Superoxide dismutase activity, oxidative damage, and mitochondrial energy metabolism in familial and sporadic amyotrophic lateral sclerosis, J Neuropathol. 61:2322 (1993).Google Scholar
  36. 36.
    J. Mitchell, J. Gatt, T. Phillips, E. Houghton, G. Roston, and C. Wignall, Cu/Zn Superoxide dismutase free radical, and motorneurone disease, Lancet. 342:1051 (1993).PubMedCrossRefGoogle Scholar
  37. 37.
    R. Lanius, C. Krieger, R. Wagey, and C. Shaw, Increased [35S]glutathione binding sites in spinal cords from patients with sporadic amyotrophic lateral, Neurosci Lett. 163:89 (1993).PubMedCrossRefGoogle Scholar
  38. 38.
    A. Shibata Noriuki, M. Hirano, and K. Kobayashi, Immunohistochemical demonstration of Cu/Zn Superoxide dismutase in the spinal cord of patients with familial amyotrophic lateral sclerosis, Acta Histochem Cytochem. 26:619 (1993).CrossRefGoogle Scholar
  39. 39.
    N. Shibata, A. Hirano, M. Kobayashi, S. Sasaki, T. Kato, S. Matsumoto, Z. Shiozawa, T. Komori, A. Ikemoto, T. Umahara, and K. Asayama, Cu/Zn Superoxide dismutase-like immunoreactivity in Lewy body-like inclusions of sporadic amyotrophic lateral sclerosis, Neurosci Lett. 179:149 (1994).PubMedCrossRefGoogle Scholar
  40. 40.
    D. J. Kane, T. A. Sarafian, A. Rein, H. Hahn, E. Butler Gralla, J. Selverstone Valentine, T. Örd, and D. E. Bredesen, Bcl-2 inhibition of neural death: decreased generation of reactive oxygen species, Science. 262:1274 (1993).PubMedCrossRefGoogle Scholar
  41. 41.
    D. M. Hockenbery, Z. N. Oltvai, X.-M. Yin, C. L. Milliman, and S. J. Korsmeyer, Bcl-2 functions in an antioxidant pathway to prevent apoptosis, Cell. 75:241 (1993).PubMedCrossRefGoogle Scholar
  42. 42.
    A. Plaitakis, Glutamate dysfunction and selective motor neuron degeneration in Amyotrophic Lateral Sclerosis: A hypothesis, Ann Neurol 28:3 (1990).PubMedCrossRefGoogle Scholar
  43. 43.
    J. D. Rothstein, L. J. Martin, and R. W. Kuncl, Decrease glutamate transport by the brain and spinal cord in Amyotrophic Lateral Sclerosis, N Engl J Med. 326:1464 (1992).PubMedCrossRefGoogle Scholar
  44. 44.
    J. D. Rothstein, J. Lin, M. Dykes-Hoberg, and R. W. Kuncl, Chronic inhibition of glutamate uptake produces a model of slow neurotoxicity, Proc Natl Acad Sci USA. 90:6591 (1993).PubMedCrossRefGoogle Scholar
  45. 45.
    J. T. Coyle, and P. Puttfarcken, Oxidative stress, glutamate, and neurodegenerative disorders, Science. 262:689 (1993).PubMedCrossRefGoogle Scholar
  46. 46.
    M. Lafon-Cazal, M. Culcasi, F. Gaven, S. Pietri, and J. Bockaert, Nitric oxide, Superoxide dismutase and peroxynitrite: putative mediators of NMDA-induced cell death in cerebellar granule cells, Neuropharmac. 32:1259 (1993).CrossRefGoogle Scholar
  47. 47.
    M. Lafon-Cazal, S. Pietri, M. Culcasi, and J. Bockaert, NMDA-dependent Superoxide production and neurotoxicity, Nature. 364:535 (1993).PubMedCrossRefGoogle Scholar
  48. 48.
    A. Y. Sun, Y. Cheng, Q. Bu, and F. Oldfield, The biochemical mechanisms of the excitotoxicity of kainic acid, Mol Chem Neuropathol 17:51 (1992).PubMedCrossRefGoogle Scholar
  49. 49.
    J. A. Dykens, A. Stern, and E. Trenker, Mechanism of kainate toxicity to cerebellar neurons in vitro is analogous to reperfusion tissue injury, J Neuropathol. 49:1222 (1987).Google Scholar
  50. 50.
    J. Williams, M. Errington, M. Lynch, and T. Bliss, Arachidonic acid induces a long-term activity-dependent enhancement of synaptic transmission in the hippocampus, Nature. 341:739 (1989).PubMedCrossRefGoogle Scholar
  51. 51.
    J. Lazarewicz, J. Wroblewski, M. Palmer, and E. Costa, Activation of N-methyl-D-aspartate-sensitive glutamate receptors stimulates arachidonic acid release in primary cultures of cerebellar granule cells, Pharmacology. 27:765 (1988).Google Scholar
  52. 52.
    A. Dumuis, M. Sebben, L. Haynes, J.-P. Pin, and J. Bockaert, NMDA receptors activate the arachidonic acid cascade system in striatal neurons, Nature. 336:68 (1988).PubMedCrossRefGoogle Scholar
  53. 53.
    S. A. Upton, Y.-B. Choi, Z.-H. Pan, S. Z. Lei, H.-S. V. Chen, J. Loscalzo, D. J. Singel, and J. S. Stamler, A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds, Nature. 364:626 (1993).CrossRefGoogle Scholar
  54. 54.
    V. L. Dawson, T. M. Dawson, D. A. Bartley, G. R. Uhl, and S. H. Snyder, Mechanisms of nitric oxide-mediated neurotoxicity in primary brain cultures, J Neuroscl 13:2651 (1993).Google Scholar
  55. 55.
    T. M. Dawson, V. L. Dawson, and S. H. Snyder, A novel neuronal messenger molecule in brain: the free radical nitric oxide, Ann Neurol 32:297 (1992).PubMedCrossRefGoogle Scholar
  56. 56.
    J. S. Beckman, T. W. Beekman, J. Chen, P. A. Marshall, and B. A. Freeman, Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and lsuperoxide, Proc Natl Acad Sci USA. 87:1620 (1990).PubMedCrossRefGoogle Scholar
  57. 57.
    T. Kawamata, H. Akiyama, T. Yamada, and P. L. McGeer, Immunologie reactions in Amyotrophic Lateral Sclerosis brain and spinal cord tissue., Am J Pathol 140:691 (1992).PubMedGoogle Scholar
  58. 58.
    C. A. Colton, and D. L. Gilbert, Production of Superoxide anions by a CNS macrophage, the microglia, FEBS Lett. 223:284 (1987).PubMedCrossRefGoogle Scholar
  59. 59.
    M. Tanaka, A. Sotomatsu, T. Yoshida, T. Hirai, and A. Nishida, Detection of Superoxide production by activated microglia using a sensitive and specific chemiluminescence assay and microglia-mediated PC12h cell death, J Neuropathol. 63:266 (1994).Google Scholar
  60. 60.
    S. B. Corradin, J. Mauel, S. DenisDonini, E. Quattrocchi, and P. Ricciardi-Castagloni, Inducible nitric oxide synthase activity of cloned murine microglial cells, Glia. 7:255 (1993).PubMedCrossRefGoogle Scholar
  61. 61.
    B. Halliwell, and J. M. Gutteridge, Free radicals in biology and medicine, in: Second ed. Oxford: Clarendon Press, 1989.Google Scholar
  62. 62.
    P. G. Iannuzzelli, X. H. Wang, Y. Wang, and E. H. Murphy, Axotomy-induced changes in cytochrome oxidase activity in the cat trochlear nucleus, Brain Res. 637:267 (1994).PubMedCrossRefGoogle Scholar
  63. 63.
    M. F. Beal, B. T. Hyman, and W. Koroshetz, Do defects in mitochondrial energy metabolism underlie the pathology of neurodegenerative diseases?, TINS. 16:125 (1993).PubMedGoogle Scholar
  64. 64.
    H. Mohammed, J. Cummings, T. Divers, B. Valentine, A. de Lahunta, B. Summers, B. Farrow, K. Trembicki-Graves, and A. Mauskopf, Risk factors associated with equine motor neuron disease: a possible model for human MND, Neurology. 43:966 (1993).PubMedCrossRefGoogle Scholar
  65. 65.
    J. D. Rothstein, L. A. Bristol, B. Hosier, R. H. J. Brown, and R. W. Kuncl, Chronic inhibition of Superoxide dismutase produces apoptotic death of spinal neurons, Proc Natl Acad Sci USA. 91:4155 (1994).PubMedCrossRefGoogle Scholar
  66. 66.
    C. M. Troy, and M. L. Shelanski, Down-regulation of copper/zinc Superoxide dismutase causes apoptotic cell death, Proc Natl Acad Sci USA. 91:6384 (1994).PubMedCrossRefGoogle Scholar
  67. 67.
    C. A. Pardo, Z. Xu, D. R. Borchelt, D. L. Price, S. Sisodia, and D. W. Cleveland, Superoxide dismutase is an abundant component in cell bodies, dendrites, and axons of motor neurons and in a subset of other neurons, Proc Natl Acad Sci USA. 92:954 (1995).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Catherine Bergeron
    • 1
    • 2
  • Connie Petrunka
    • 1
  • Luitgard Weyer
    • 1
  1. 1.Centre for Research in Neurodegenerative Diseases and Department of PathologyUniversity of TorontoTorontoCanada
  2. 2.Department of PathologyThe Toronto HospitalTorontoCanada

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