Oxidative stress and motor neurone disease

Brain Pathology

Volumn 9, Issue 1, 1999, Pages 165-186

  Cookson, Mark R ^a   Shaw, Pamela J ^a  

^a NEWCASTLE UNIVERSITY   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

COPPER; COPPER ZINC SUPEROXIDE DISMUTASE; FREE RADICAL; NEUROFILAMENT PROTEIN; PEROXYNITRITE; ZINC;

AGING; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; CONFERENCE PAPER; CONTROLLED STUDY; DETERIORATION; HUMAN; MOTOR NEURON DISEASE; MOUSE; NERVE DEGENERATION; NEUROTOXICITY; NONHUMAN; OXIDATIVE STRESS; POINT MUTATION; PROTEIN AGGREGATION; PROTEIN DOMAIN; TRANSGENIC MOUSE;

EID: 0032949602     PISSN: 10156305     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.1750-3639.1999.tb00217.x     Document Type: Conference Paper

References (148)

1. Abe K, Pan LH, Watanabe M, Konno H, Kato T, Itoyama Y (1997) Upregulation of protein-tyrosine nitration in the anterior horn cells of amyotrophic lateral sclerosis. Neurol Res 19: 124-128
2. Abe K, Pan L-H, Watanabe M, Kato T, Itoyama Y (1995) Induction of nitrotyrosine-like immunoreactivity in the lower motor neuron of amyotrophic lateral sclerosis. Neurosci Lett 199: 152-154
3. Aguirre T, VanDenBosch L, Goetschalckx K, Tilkin P, Mathijs G, Cassiman JJ, Robberecht W (1998) Increased sensitivity of fibroblasts from amyotrophic lateral sclerosis patients to oxidative stress. Ann Neurol 43: 452-457
4. Bajaj NPS, AlSarraj ST, Anderson V, Kibble M, Leigh N, Miller CCJ (1998) Cyclin-dependent kinase-5 is associated with lipofuscin in motor neurones in amyotrophic lateral sclerosis. Neurosci Lett 245: 45-48
5. Beal MF, Ferrante RJ, Browne SE, Matthews RT, Kowall NW, Brown RH (1997) Increased 3-nitrotyrosine in both sporadic and familial amyotrophic lateral sclerosis Ann Neurol 42: 644-654
6. Beal MF, Hyman BT, Koroshetz W (1993) Do defects in mitochondrial energy metabolism underlie the pathology of neurodegenerative disease? Trends Neurol Sci 16: 125-131
7. Beckman JS, Carson M, Smith CD, Koppenol WH (1993) ALS, SOD and peroxynitrite. Nature 364: 584
8. Bensimon G, Lacomblez V, Meininger V, ALS/Riluzole study group (1994) A controlled trial of riluzole in amyotrophic lateral sclerosis. N Engl J Med 330: 585-591
9. Bergeron C, Muntasser S, Somerville MJ. Weyer L, Percy ME (1994) Copper/Zinc superoxide dismutase messenger RNA levels are increased in sporadic amyotrophic lateral sclerosis motor neurons Brain Res 659. 272-276
10. Bergeron C, Petrunka C, Weyer L (1996) Copper/Zinc Superoxide Dismutase expression in the human central nervous system - correlation with selective neuronal vulnerability. Am J Pathol 148: 273-279
11. Bogdanov MB, Ramos LE, Xu Z, Beal MF (1998) Elevated "hydroxyl radical" generation in vivo in an animal model of amyotrophic lateral sclerosis. J Neurochem 71: 1321-1324
12. Bolaños JP, Heales SJR, Land JM, Clark JB (1995) Effect of peroxynitrite on mitochondrial respiratory chain: differential susceptibility of neurones and astrocytes in primary culture. J Neurochem 64: 1965-1972
13. Borchelt DR, Lee MK, Slunt HS, Guarnieri M, Xu ZS, Wong PC, Brown RH, Price DL, Sisodia SS, Cleveland DW (1994) Superoxide dismutase-1 with mutations linked to familial amyotrophic lateral sclerosis possesses significant activity. Proc Natl Acad Sci USA 91: 8292-8296
14. Borchelt DR, Wong PC, Becher MW, Pardo CA, Lee MK, Xu Z-S, Thinakaran G, Jenkins NA, Copeland NG, Sisodia SS, Cleveland DW, Price DL, Hoffman PN (1998) Axonal transport of mutant superoxide dismutase 1 and focal axonal abnormalities in the proximal axons of transgenic mice. Neurobiol Dis 5: 27-35
15. Bowling AC, Schulz JB, Brown RH, Beal MF (1993) Superoxide dismutase activity, oxidative damage, and mitochondrial energy metabolism in familial and sporadic amyotrophic lateral sclerosis. J Neurochem 61: 2322-2325
16. Brierly EJ, Johnson MA, James OFW, Turnbull DM (1997) Mitochondrial involvement in the ageing process. Facts and controversies. Mol Cell Biochem 174: 325-328
17. Brown RH (1995) Amyotrophic lateral sclerosis - Recent insights from genetics and transgenic mice. Cell 80: 687-692
18. Bruijn LI, Beal MF, Becher MW, Schulz JB, Wong PC, Price DL, Cleveland DW (1997) Elevated free nitrotyrosine levels, but not protein-bound nitrotyrosine or hydroxyl radicals, throughout amyotrophic lateral sclerosis (ALS)-like disease implicate tyrosine nitration as an aberrant in vivo property of one familial ALS-linked superoxide dismutase 1 mutant. Proc Natl Acad Sci USA 94: 7606-7611
19. Bruijn LI, Becher MW, Lee MK, Anderson KL, Jenkins NA, Copeland NG, Sisodia SS, Rothstein JD, Borchelt DR, Price DL, Cleveland DW (1997) ALS-linked SOD1 mutant G85R mediates damage to astrocytes and promotes rapidly progressive disease with SOD1-containing inclusions. Neuron 18: 327-338
20. Bruijn LI, Cleveland DW (1996) Mechanisms of selective motor neuron death in ALS: Insights from transgenic mouse models of motor neuron disease Neuropathol Appl Neurobiol 22: 373-387
21. 2+ concentration in transfected neuroblastoma SH-SY5Y cels. FEBS Letts 414: 365-368
22. Carriedo SG, Yin HZ, Weiss JH (1996) Motor neurons are selectively vulnerable to AMPA/kainate receptor-mediated injury in vitro. J Neurosci 16: 4069-4079
23. Chou SM, Wang HS, Komai K (1996) Colocalization of NOS and SOD1 in neurofilament accumulation within motor neurons of amyotrophic lateral sclerosis - an immunohistochemical study. J Chem Neuroanat 10: 249-258
24. Chou SM, Wang HS, Taniguchi A (1996) Role of SOD-1 and nitric oxide cyclic GMP cascade on neurofilament aggregation in ALS/MND. J Neurol Sci 139: 16-26
25. Cleveland DW, Bruijn LI, Wong PC, Marszalek JR, Vechio JD, Lee MK, Xu XS, Borchelt DR, Sisodia SS, Price DL (1996) Mechanisms of selective motor neuron death in transgenic mouse models of motor neuron disease. Neurology 47: S 54-S 61
26. Comi GP, Bordoni A, Salani S, Franceschina L, Sciacco M, Prelle A, Fortunato F, Zeviani M, Napoli L, Bresolin N, Moggio M, Ausenda CD, Taanman J-W, Scarlato G (1998) Cytochrome c Oxidase subunit I microdeletion in a patient with motor neuron disease. Ann Neurol 43: 110-116
27. Cookson MR, Ince PG, Shaw PJ (1998) Peroxynitrite and hydrogen peroxide induced cell death in the NSC34 neuroblastoma X spinal cord cell line; Role of poly(ADP-ribose) polymerase. J Neurochem 72: 501-508
28. Cookson MR, Ince PG, Usher PA, Shaw PJ (1998) Distribution of poly(ADP-ribose) polymerase (PARP) in the human CNS and in amyotrophic lateral sclerosis. J Neuropath Exp Neurol Submitted
29. Cookson MR, Thatcher MM, Ince PG, Shaw PJ (1996) Selective loss of neurofilament proteins after exposure of differentiated human IMR32 neuroblastoma cells to oxidative stress. Brain Res 738: 162-166
30. Corral-Debrinski M, Norton T, Lott MT, Shoffner JM, Beal MF, Wallace DC (1992) Mitochondrial DNA deletions in human brain: regional variability and increase with increased age. Nat Gen 2: 324-329
31. Corson LB, Strain JJ, Culotta VC, Cleveland DW (1998) Chaperone-facilitated copper binding is a property common to several classes of familial amyotrophic lateral sclerosis-linked superoxide dismutase mutants. Proc Natl Acad Sci USA 95: 6361-6366
32. Cosi C, Chopin P, Marien M (1996) Benzamide, an inhibitor of poly(ADP-ribose) polymerase attenuates methamphetamine-induced dopamine toxicity in the C57B1/6N mouse. Brain Res 735: 343-348
33. Cosi C, Colpaert F, Koek W, Degryse A, Marien M (1996) Poly(ADP-ribose) polymerase inhibitors protect against MPTP-induced depletions of striatal dopamine and coritcal noradrenaline in C57B1/6 mice. Brain Res 729: 264-269
34. Cosi C, Suzuki H, Milani D, Facci L, Menegazzi M, Vantini G, Kanai Y, Skapper SD (1994) Poly(ADP-Ribose) Polymerase: early involvement in glutamate-induced neurotoxicity in cultured cerebeltar granule cells. J Neurosci Res 39: 38-46
35. Cote F, Collard JF, Julien JP (1993) Progressive neuronopathy in transgenic mice expressing the human neurofilament heavy gene - a mouse model of amyotrophic lateral sclerosis. Cell 73: 35-46
36. Couillard-Despres S, Zhu Q, Wong PC, Price DL, Cleveland DW, Julian J-P (1998) Protective effect of neurofilament heavy gene in motor neuron disease induced by mutant superoxide dismutase. Proc Natl Acad Sci USA 95: 9626-9630
37. Crow JP, Sampson JB, Zhuang YX, Thompson JA, Beckman JS (1997) Decreased zinc affinity of amyotrophic lateral sclerosis-associated superoxide dismutase mutants leads to enhanced catalysis of tyrosine nitration by peroxynitrite. J Neurochem 69: 1936-1944
38. Crow JP, Ye YZ, Strong M, Kirk M, Barnes S, Beckman JS (1997) Superoxide dismutase catalyzes nitration of tyrosines by peroxynitrite in the rod and head domains of neurofilament-L. J Neurochem 69: 1945-1953
39. Cudkowicz ME, McKennaYasek D, Chen C, HedleyWhyte ET, Brown RH (1998) Limited corticospinal tract involvement in amyotrophic lateral sclerosis subjects with the A4V mutation in the copper/zinc superoxide dismutase gene Ann Neurol 43: 703-710
40. Curti D, Malaspina A, Facchetti G, Camana C, Mazzini L, Tosca P, Zerbi F, Ceroni M (1996) Amyotrophic lateral sclerosis: oxidative energy metabolism and calcium homeostasis in peripheral blood lymphocytes. Neurology 47: 1061-1064
41. DalCanto MC, Gurney ME (1994) Development of central nervous system pathology in a murine transgenic model of human amyotrophic lateral sclerosis. Am J Pathol 145: 1271-1279
42. DalCanto MC, Gurney ME (1995) Neuropathological changes in 2 lines of mice carrying a transgene for mutant human Cu,Zn SOD, and in mice overexpressing wild-type human SOD - a model of familial amyotrophic lateral sclerosis (FALS). Brain Res 676: 25-40
43. DalCanto MC, Gurney ME (1997) A low expressor line of transgenic mice carrying a mutant human Cu,Zn superoxide dismutase [SOD1] gene develops pathological changes that most closely resemble those in human amyotrophic lateral sclerosis. Acta Neuropath 93: 537-550
44. Dawson VL, Dawson TM (1997) Therapeutic approaches with nitric oxide synthase inhibitors. In Mitochondria and free radicals in neurodegenerative diseases Beal MF, Howell N,Bodis-Woliner I (Eds.),pp. 513-535, Wiley-Liss, New York
45. Deng H-X, Hentati A, Tainer JA, Iqbal Z, Cayabyab A, Hung W-Y, Getzoff ED, Hu P, Herzfeldt B, Roos RR Warner C, Deng G, Soriano E, Smyth C, Parge HE, Ahmed A, Roses AD, Hallewell RA, Pericak-Vance MA, Siddique T (1993) Amyotrophic lateral sclerosis and structural defects in Cu Zn superoxide dismutase Science 261: 1047-1051
46. Durham HD, Roy J, Dong L, Figlewicz DA (1997) Aggregation of mutant Cu/Zn superoxide dismutase proteins in a culture model of ALS. J Neuropath Exp Neurol 56: 523-530
47. Eliasson MJL, Sampei K, Mandir AS, Hurn PD, Traystman RJ, Bao J, Pieper A, Wang Z-Q, Dawson TM, Snyder SH, Dawson VL (1997) Poly(ADP-ribose) polymerase gene disruption renders mice resistant to cerebral ischemia. Nat Med 3: 1089-1095
48. Eyer J, Cleveland DW, Wong PC, Peterson AC (1998) Pathogenesis of two axonopathies does not require axonal neurofilaments. Nature 391: 584-587
49. Ferrante RJ, Browne SE, Shinobu LA, Bowling AC, Baik MJ, MacGarvey U, Kowall NW, Brown RH, Beal MF (1997) Evidence of increased oxidative damage in both sporadic and familial amyotrophic lateral sclerosis. J Neurochem 69: 2064-2074
50. Ferrante RJ, Shinobu LA, Schulz JB, Matthews RT, Thomas CE, Kowall NW, Gurney ME, Beal MF (1997) Increased 3-nitrotyrosine and oxidative damage in mice with a human copper/zinc superoxide dismutase mutation. Ann Neurol 42: 326-334
51. Figlewicz DA, Krizus A, Martinoli MG, Meininger V, Dib M, Rouleau GA, Julien JP (1994) Variants of the heavy neurofilament subunit are associated with the development of amyotrophic lateral sclerosis. Hum Mol Gen 3: 1757-1761
52. Fitzmaurice PS, Shaw IC, Kleiner HE, Miller RT, Monks TJ, Lau SS, Mitchell JD, Lynch PG (1996) Evidence for DNA damage in amyotrophic lateral sclerosis. Muscle and Nerve 19: 797-798
53. Fray AE, Ince PG, Banner SJ, Milton ID, Usher PA, Cookson MR, Shaw PJ (1998) The expression of the glial glutamate transporter protein EAAT2 in motor neuron disease: an immunohistochemical study. Eur J Neurosci 10: 2481-2489
54. Friedlander RM, Brown RH, Gagliardini V, Wang J, Yuan JY (1997) inhibition of ICE slows ALS in mice. Nature 388: 31
55. Fujita K, Yamauchi M, Shibayama K, Ando M, Honda M, Nagata Y (1996) Decreased cytochrome c oxidase activity but unchanged superoxide dismutase and glutathione peroxidase activities in the spinal cords of patients with amyotrophic lateral sclerosis. J Neurosci Res 45: 276-281
56. Ghadge GD, Lee JP, Bindokas VP, Jordan J, Ma L, Miller RJ, Roos RP (1997) Mutant superoxide dismutase-1-linked familial amyotrophic lateral sclerosis: Molecular mechanisms of neuronal death and protection. J Neurosci 17: 8756-8766
57. Giasson BI, Mushynski WE (1996) Aberrant stress-induced phosphorylation of perikaryal neurofilaments. J Biol Chem 48: 30404-30409
58. Greene JG, Sheu S-S, Gross RA, Greenamyre JT (1998) 3-nitroproprionic acid exacerbates N-methyl-D-aspartate toxicity in striatal culture by mutliple mechanisms. Neuroscience 84: 503-510
59. Guidato S, Bajaj NPS, Miller CCJ (1996) Cellular phosphorylation of neurofilament heavy-chain by cyclin-dependent kinase-5 masks the epitope for monoclonal-antibody N52. Neurosci Lett 217: 157-160
60. Guidato S, Tsai LH, Woodgett J, Miller CCJ (1996) Differential cellular phosphorylation of neurofilament heavy side- arms by glycogen-synthase kinase-3 and cyclin-dependent kinase-5. J Neurochem 66: 1698-1706
61. Gurney ME, Cutting FB, Zhai P, Doble A, Taylor CP, Andrus PK, Hall ED (1996) Benefit of Vitamin E, riluzole and gabapentin in a transgenic mouse model of familial amyotrophic lateral sclerosis. Ann Neurol 39: 147-157
62. Gurney ME, Pu HF, Chiu AY, Dalcanto MC, Polchow CY, Alexander DD, Caliendo J, Hentati A, Kwon YW, Deng HX, Chen WJ, Zhai P, Sufit RL, Siddique T (1994) Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation. Science 264: 1772-1775
63. Hoffman EK, Wilcox HM, Scott RW, Siman R (1996) Proteasome inhibition enhances the stability of mouse Cu/Zn superoxide dismutase with mutations linked to familial amyotrophic lateral sclerosis. J Neurol Sci 139: 15-20
64. Hottinger AF, Fine EG, Gurney ME, Zurn AD, Aebischer P (1997) The copper chelator d-penicillamine delays onset of disease and extends survival in a transgenic mouse model of familial amyotrophic lateral sclerosis. Eur J Neurosci 9: 1548-1551
65. Ince PG, Shaw PJ, Candy JM, Mantle D, Tandon L, Ehmann WD, Markesbery WR (1994) Iron, selenium and glutathione peroxidase activity are elevated in sporadic motor neuron disease. Neurosci Lett 182: 87-90
66. Ince PG, Stout N, Shaw PJ, Slade J, Hunziker W, Heizmann CW, Baimbridge KG (1991) Parvalbumin and calbindin D-28k in the human motor system and in motor neuron disease Neuropathol Appl Neurobiol 19: 291-299
67. Ince PG, Tomkins J, Slade JY, Thatcher NM, Shaw PJ (1998) Amyotrophic lateral sclerosis associated with genetic abnormalities in the gene encoding Cu/Zn superoxide dismutase: molecular pathology of five new cases, and comparison with previous reports and 73 cases of sporadic ALS. J Neuropath Exp Neurol In Press
68. Ishiropolous H, Al-Mehdi AB (1995) Peroxynitrite-mediated oxidative protein modifications. FEBS Letts 364: 279-282
69. Jordan J, Gallindo MF, Prehn JHM, Weichselbaum RR, Beckett M, Ghadge GD, Roos RP, Leiden JM, Miller RJ (1997) p53 expression induces apoptosis in hippocampal pyramidal neuron cultures. J Neurosci 17. 1397-1405
70. Kato S, Hayashi H, Nakashima K, Nanba E, Kato M, Hirano A, Nakano I, Asayama K, Ohama E (1997) Pathological characterization of astrocytic hyaline inclusions in familial amyotrophic lateral sclerosis. Am J Pathol 151: 611-620
71. Kato S, Shimoda M, Watanabe Y, Nakasmia K, Takahashi K, Omaha E (1996) Familial amyotrophic lateral sclerosis with a two base pair deletion in superoxide dismutase 1 gene: multisystem degeneration with intracytoplasmic hyaline inclusions in astrocytes. J Neuropath Exp Neurol 55: 1089-1101
72. Kisby GE, Milne J, Sweatt C (1997) Evidence of reduced DNA repair in amyotrophic lateral sclerosis brain tissue. Neuroreport 8: 1337-1340
73. Kong J, Xu Z (1998) Massive mitochondrial degeneration in motor neurons triggers the onset of amyotrophic lateral sclerosis in mice carrying a mutant SOD1 J Neurosci 18: 3241-3250
74. Kostic V, Jackson-Lewis V, deBilbao F, Dubois-Dauphin M, Przedborski S (1997) Bcl-2: prolonging life in a transgenic mouse model of familial amyotrophic lateral sclerosis. Science 277: 559-562
75. Kyriakis JM, Avruch J (1996) Sounding the alarm: protein kinase cascades activated by stress and inflammation J Biol Chem 271: 24313-24316
76. Lacomblez L, Bensimon G, Leigh PN, Guillet P, Meninger V, ALS/Riluzole study group 11 (1996) Dose-ranging study of riluzole in amyotrophic lateral sclerosis. Lancet 347: 1425-1431
77. Lee MK, Marszalek JR, Cleveland DW (1994) A mutant neurofilament subunit causes massive, selective motor neuron death: implications for the pathogenesis of human motor neuron disease. Neuron 13: 975-988
78. Lefebvre S, Mushynski WE (1987) Calcium binding to untreated and dephosphorylated porcine neurofilaments. Biochem Biophys Res Comms 145: 1006-1011
79. Lefebvre S, Mushynski WE (1988) Characterization of the cation binding properties of porcine neurofilaments. Biochemistry 27: 8503-8508
80. Linnane AW, Marzuki S, Ozawa T, Tanaka M (1989) Mitochondrial DNA mutations as an important contribution to ageing and degenerative diseases. Lancet 642-645
81. Liochev SI, Chen LL, Hallewell RA, Fridovich I (1997) Superoxide-dependent peroxidase activity of H48Q: a superoxide dismutase variant associated with familial amyotrophic lateral sclerosis. Arch Biochem Biophys 346 263-268
82. Louvel E, Hugon J, Doble A (1997) Therapeutic advances in amyotrophic lateral sclerosis. Trends Pharmacol Sci 18: 196-203
83. Louwerse ES, Weverling GJ, Bossuyt PMM, Posthumus Meyjes FE, deJong JMBV (1995) Randomized, double-blind controlled trial of acetylcysteine in amyotrophic lateral sclerosis. Arch Neurol 52: 559-564
84. Mena MA, Khan U, Togasaki DM, Sulzer D, Epstein CJ, Przedborski S (1997) Effects of wild-type and mutated copper/zinc superoxide dismutase on neuronal survival and L-DOPA-induced toxtcity in postnatal midbrain culture. J Neurochem 69: 21-33
85. Migheli A, Attanasio A, Schiffer D (1994) Ubiquitin and neurofilament expression in anterior horn cells in amyotrophic lateral sclerosis: possible clues to the pathogenesis. Neuropathol Appl Neurobiol 20: 282-289
86. Miller RJ (1998) Mitochondria - the Kraken wakesl Trends Neurosci 21: 95-97
87. Morrison BM, Gordon JW, Ripps ME, Morrison JH (1996) Quantitative immunocytochemical analysis of the spinal cord in G86R superoxide dismutase transgenic mice - neurochemical correlates of selective vulnerability. J Comp Neurol 373: 619-631
88. Mourelatos Z, Gonatas NK, Stieber A, Gurney ME, Dalcanto MC (1996) The golgi apparatus of spinal cord motor neurons in transgenic mice expressing mutant Cu,Zn superoxide dismutase becomes fragmented in early, preclinical stages of the disease. Proc Natl Acad Sci USA 93: 5472-5477
89. Mu XJ, He J, Anderson DW, Trojanowski JQ, Springer JE (1996) Altered expression of Bcl-2 and Bax messenger RNA in amyotrophic lateral sclerosis spinal cord motor neurons Ann Neurol 40: 379-386
90. Munoz DG, Greene C, Perl DP. Selkoe DJ (1988) Accumulation of phosphorylated neurofilaments in anterior horn motorneurons of amyotrophic lateral sclerosis patients. J Neuropath Exp Neurol 47: 9-18
91. Murayama S, Ookawa Y, Mori H, Nakano I, Ihara Y, Kuzuhara S, Tomonaga M (1989) Immunocytochemical and ultrasructural study of Lewy-body-like hyaline inclusions in familial amyotrophic lateral sclerosis. Acta Neuropath 78: 143-152
92. Olkowski ZL (1998) Mutant AP endonuclease in patients with amyotrophic lateral sclerosis. Neuroreport 9: 239-242
93. Oorschot DE, McLennan IS (1998) The trophic requirements of mature motorneurons. Brain Res 789: 315-321
94. Orrell RW, King AW, Hilton DA, Campbell MJ, Lane RJM, DeBelleroche JS (1995) Familial amyotrophic lateral sclerosis with a point mutation of SOD-1 - intrafamilial heterogeneity of disease duration associated with neurofibrillary tangles. J Neurol Neurosurg Psychiat 59: 266-270
95. Packer MA, Scarlett JL, Martin SW, Murphy MP (1997) Induction of the mitochondrial permeability transition pore by peroxynitrite. Biochem Soc Trans 25
96. Pardo CA, Xu ZS, Borchelt DR, Price DL, Sisodia SS, Cleveland DW (1995) 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: 954-958
97. Phillips JP, Tainer JA, Getzoff ED, Boulianne GL, Kirby K, Hilliker AJ (1995) Subunit-destabilising mutations in Drosophila copper/zinc superoxide dismutase: neuropathology and a model of dimer dysequilibriurn Proc Natl Acad Sci USA 92: 8533-8534
98. Pramatarova A, Goto J, Nanba E, Nakashima K, Takahashi K, Takagi A, Kanazawa I, Figlewicz DA, Rouleau GA (1994) A 2 basepair deletion in the SOD-1 gene causes familial amyotrophic lateral sclerosis. Hum Mol Gen 3: 2061-2062
99. Przedborski S, Donaldson DM, Jakowec M, Kish SJ, Guttman M, Rosoklija G, Hays AP (1996) Brain superoxide dismutase, catalase and glutathione peroxidase in amyotrophic lateral sclerosis. Ann Neurol 39: 158-165
100. Rabizadeh S, Gralla EB, Borchelt DR, Gwinn R, Valentine JS, Sisodia S, Wong P, Lee M, Hahn H, Bredesen DE (1995) Mutations associated with amyotrophic lateral sclerosis convert superoxide dismutase from an antiapoptotic gene to a proapoptotic gene - studies in yeast and neural cells. Proc Natl Acad Sci USA 92. 3024-3028
101. Radunovic A, Leigh PN (1996) Cu/Zn superoxide dismutase gene mutations in amyotrophic lateral sclerosis: Correlation between genotype and clinical features J Neurol Neurosurg Psychiat 61: 565-572
102. Reaume AG, Elliott JL, Hoffman EK, Kowall NW, Ferrante RJ, Siwek DF, Wilcox HM, Flood DG, Beal MF, Brown RH, Scott RW, Snider WD (1996) Motor neurons in Cu/Zn superoxide dismutase-deficient mice develop normally but exhibit enhanced cell death after axonal injury. Nat Gen 13: 43-47
103. Reed JC (1997) Double identitiy for proteins of the Bcl-2 family. Nature 387: 773-776
104. Regan RF (1996) The vulnerability of spinal cord neurons to excitotoxic injury: comparisons with cortical neurons. Neurosci Lett 213: 9-12
105. Richter C (1995) Oxidative damage to mitochondrial DNA and its relationship to ageing. Intl J Biochem Cell Biol 27: 647-753
106. Ripps ME, Huntley GW, Hof PR, Morrison JH, Gordon JW (1995) Transgenic mice expressing an altered murine superoxide dismutase gene provide an animal model of amyotrophic lateral sclerosis. Proc Natl Acad Sci USA 92: 689-693
107. Rosen DR, Siddique T, Patterson D, Figlewicz DA, Sapp P, Hentati A, Donaldson D, Goto J, Oregan JP, Deng HX Rahmant Z, Krizus A, McKennayasek D, Cayabyab A, Gaston SM, Berger R, Tanzi RE, Halperin JJ, Herzfeldt B. Vandenbergh R, Hung WY, Bird T, Deng G, Mulder DW. Smyth C, Laing NG, Soriano E, Pericakvance MA, Haines J, Rouleau GA, Gusella JS, Horvitz HR, Brown RH (1993) Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362: 59-62
108. Rothstein JD (1995) Excitotoxic mechanisms in the pathogenesis of amyotrophic lateral sclerosis. Adv Neurol 68: 7-20
109. Rothstein JD, Bristol LA, Hosler B, Brown RH, Kuncl RW (1994) Chronic inhibition of superoxide dismutase produces apoptotic death of spinal neurons. Proc Natl Acad Sci USA 91: 4155-4159
110. Rothstein JD, Kammen MV, Levy AI, Martin LJ, Kuncl RW (1995) Selective loss of glial glutamate transporter GLT-1 in amyotrophic lateral sclerosis. Ann Neurol 38: 73-84
111. Rouleau GA, Clark AW, Rooke K, Pramatarova A, Krizus A, Suchowersky O, Julien JP, Figlewicz D (1996) Sod1 mutation is associated with accumulation of neurofilaments in amyotrophic lateral sclerosis. Ann Neurol 39: 128-131
112. Sasaki S, Iwata M (1996) Ultrastructural study of synapses in the anterior horn of patients with amyotrophic lateral sclerosis. Neurosci Lett 204: 53-56
113. Shaw CE, Enayat ZE, Chioza BA, AlChalabi A, Radunovic A, Powell JR Leigh P (1998) Mutations in all five exons of SOD-1 may cause ALS. Ann Neurol 43. 390-393
114. Shaw CE, Enayat ZE, Powell JF, Anderson VER, Radunovic A, AlSarraj S, Leigh PN (1997) Familial amyotrophic lateral sclerosis - Molecular pathology of a patient with a SOD1 mutation. Neurology 49: 1612-1616
115. Shaw PJ (1994) Excitotoxicity and motor neurone disease: a review of the evidence. J Neurol Sci 124(suppl.): 6-13
116. Shaw PJ, Chinnery RM, Thagesen H, Borthwick GM, Ince PG (1997) Immunocytochemical study of the distribution of the free radical scavenging enzymes Cu/Zn superoxide dismutase (SOD1); Mn superoxide dismutase (Mn SOD) and catalase in the normal human spinal cord and in motor neuron disease. J Neurol Sci 147: 115-125
117. Shaw PJ, Ince PG, Falkous G, Mantle D (1995) Oxidative damage to protein in sporadic motor neuron disease. Ann Neurol 38: 691-695
118. Shaw PJ, Tomkins J, Slade JY, Usher P, Curtis A, Bushby K, Ince PG (1997) CNS tissue Cu/Zn superoxide dismutase (SOD1) mutations in motor neurone disease (MND) Neuroreport 8: 3923-3928
119. Shibata N, Hirano A, Kobayashi M, DalCanto MC, Gurney ME, Ikeda K, Horiuchi S (1997) Advanced glycosylation end products (AGE) deposition in intraneuronal hyaline inclusions (IHls) of spinal cords from familial amyotrophic lateral sclerosis (ALS) patients with superoxide dismutase-1 (SOD1) mutation and from transgenic mice expressing mutant human SOD1, Brain Path 7: 1073-1073
120. Shibata N, Hirano A, Kobayashi M, Siddique T, Deng HX, Hung WY, Kato T, Asayama K (1996) Intense superoxide dismutase-1 immunoreactivity in intracytoplasmic hyaline inclusions of familial amyotrophic lateral sclerosis with posterior column involvement J Neuropath Exp Neurol 55: 481-490
121. Shwartz LM, Milligan CE (1996) Cold thoughts of death: the role of ICE proteases in neuronal cell death. Trends Neurosci 19: 555-562
122. Siddique T, Nijhawan D, Hentat A (1996) Molecular genetic basis of familial ALS. Neurology 47 (suppl 2): S27-S35
123. Siklos L, Engelhardt J, Harati Y, Smith RG, Joo F, Appel SH (1996) Ultrastructural evidence for altered calcium in the motor nerve terminals in amyotrophic lateral sclerosis. Ann Neurol 39: 203-219
124. Siklos L, Engelhardt JI, Alexianu ME, Gurney ME, Siddique T, Appel SH (1998) Intracellular calcium parallels motorneuron degeneration in SOD-1 mutant mice. J Neuropath Exp Neurol 57; 571-587
125. Sillevis Smitt PAE, Mulder TPJ, Verspaget HW, Blaauwgeers HGT, Troost D, deJong JMBV (1994) Metallothionein in amyotrophic lateral sclerosis. Biol Signals 3. 193-197
126. Singh RJ, Karoui H, Gunther MR, Beckman JS, Mason RP, Kalyanaraman B (1998) Reexamination of the mechanism of hydroxyl radical adducts formed from the reaction between familial amyotrophic lateral sclerosis- associated Cu,Zn superoxide dismutase mutants and H2O2. Proc Natl Acad Sci USA 95: 6675-6680
127. Strong MJ, Stopper MM, Crow JP, Strong WL, Beckman JS (1998) Nitration of the low molecular weight neurofilament is equivalent in sporadic amyotrophic lateral sclerosis and control cervical spinal cord. Biochem Biophys Res Comms 248: 157-164
128. Szabó C, Dawson VL (1998) Role of poly(ADP-ribose) synthetase in inflammation and ischemia-reperfusion. Trends Pharmacol Sci 19: 287-297
129. Takahashi H, Makifuchi T, Nakano R, Sato S, Inuzuka T, Sakimura K, Mishina M, Honma Y, Tsuji S, Ikuta F (1994) Familial amyotrophic lateral sclerosis with a mutation in the Cu/Zn superoxide dismutase gene, Acta Neuropath 88: 185-188
130. Tomkins J, Usher P, Slade JY, Ince PG, Curtis A, Bushby K, Shaw PJ (1998) Novel insertion in the KSP region of the neurofilament heavy gene in amyotrophic lateral sclerosis. Neuroreport 9: In Press
131. Troost D, Aten J, Morsink F, Dejong J (1995) Apoptosis in amyotrophic lateral sclerosis is not restricted to motor neurons - Bcl-2 expression is increased in unaffected post- central gyrus. Neuropathol Appl Neurobiol 21: 498-504
132. Troy CM, Shelanski M (1994) Down regulation of copper/zinc superoxide dismutase causes apoptotic death in PC12 neuronal cells. Proc Natl Acad Sci USA 91: 6384-6387
133. Tu PH, Raju P, Robinson KA, Gurney ME, Trojanowski JQ, Lee VMY (1996) Transgenic mice carrying a human mutant superoxide dismutase transgene develop neuronal cytoskeletal pathology resembling human amyotrophic lateral sclerosis lesions. Proc Natl Acad Sci USA 93: 3155-3160
134. Vyth A, Timrner JG, Bossuyt PMM, Louwerse ES, deJong JMBV (1996) Survival in patients with amyotrophic lateral sclerosis, treated with an array of antioxidants. J Neurol Sci 139: 99-103
135. Wang XT, Culotta VC, Klee CB (1996) Superoxide dismutase protects calcineurin from inactivation. Nature 383: 434-437
136. Wiedau-Pazos M, Goto JJ, Rabizadeh S, Gralla EB, Roe JA, Lee MK, Valentine JS, Bredesen DE (1996) Altered reactivity of superoxide dismutase in familial amyotrophic lateral sclerosis. Science 271: 515-518
137. Wiedemann FR, Winkler K, Kuznetsov AV, Bartels C, Vielhaber S, Feistner H, Kunz WS (1998) Impairment of mitochondrial function in skeletal muscle of patients with amyotrophic lateral sclerosis. J Neurol Sci 156: 65-72
138. Williams TL, Day NC, Ince PG, Kamboj RK, Shaw PJ (1997) Calcium-permeable a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors: a molecular determinant of selective vulnerability in amyotrophic lateral sclerosis. Ann Neurol 42. 200-207
139. Williams TL, Ince PG, Oakley AE, Shaw PJ (1996) An immunocytochemical study of the distribution of AMPA selective glutamate receptor subunits in the normal human motor system. Neuroscience 74. 185-198
140. Williamson T, Bruijn LI, Zhu Q, Anderson KL, Anderson SD, Julian J-P, Cleveland DW (1998) Absence of neurofilaments reduces the selective vulnerability of motor neurons and slows disease caused by a familial amyotrophic lateral sclerosis-linked superoxide dismutase 1 mutant. Proc Natl Acad Sci USA 95: 9631-9636
141. Wong PC, Borchelt DR, Lee MK, Pardo CA, Sisodia SS, Cleveland DW, Koliatsos VE, Price DL (1996) Transgenic and gene-targeting approaches to model disorders of motor neurons. Seminars Neurosci 8: 163-169
142. Wong PC, Marszalek J, Crawford TO, Xu ZS, Hsieh ST, Griffin JW, Cleveland DW (1995) Increasing neurofilament subunit NF-M expression reduces axonal NF-H, inhibits radial growth, and results in neurofilamentous accumulation in motor-neurons J Cell Biol 130: 1413-1422
143. Wong PC, Pardo CA, Borchelt DR, Lee MK, Copeland NG, Jenkins NA, Sisodia SS, Cleveland DW, Price DL (1995) An adverse property of a familial ALS-linked SOD1 mutation causes motor-neuron disease characterized by vacuolar degeneration of mitochondria. Neuron 14: 1105-1116
144. Xu ZS, Cork LC, Griffin JW, Cleveland DW (1993) Increased expression of neurofilament subunit-NF-L produces morphological alterations that resemble the pathology of human motor- neuron disease. Cell 73. 23-33
145. Yim HS, Kang JH, Chock PB, Stadtman ER, Yim MB (1997) A familial amyotrophic lateral sclerosis associated A4V Cu/Zn superoxide dismutase mutant has a lower Km for hydrogen peroxide. J Biol Chem 272: 8861-8863
146. Yim HS, Kang JH, Yim MB, Kwak HS, Chock PB, Stadtman ER (1996) A gain-of-function of an amyotrophic lateral sclerosis- associated Cu,Zn-superoxide dismutase mutant: An enhancement of free radical formation due to a decrease in Km for hydrogen peroxide. Proc Natl Acad Sci USA 93: 5709-5714
147. Yoshiyama Y, Yamada T, Asanuma K, Asahi T (1994) Apoptosis related antigen, Le and nick-end labelling are positive in spinal motor neurons in amyotrophic lateral sclerosis. Acta Neuropath 88: 207-211
148. Zhang B, Tu PH, Abtahian F, Trojanowski JQ, Lee VMY (1997) Neurofilaments and orthograde transport are reduced in ventral root axons of transgenic mice that express human SOD1 with a G93A mutation. J Cell Biol 139: 1307-1315