Nutritional and exercise-based interventions in the treatment of amyotrophic lateral sclerosis

Clinical Nutrition

Volumn 28, Issue 6, 2009, Pages 604-617

  Patel, Barkha P ^a,b   Hamadeh, Mazen J ^a,b,c  

^a YORK UNIVERSITY   (Canada)

^b YORK UNIVERSITY   (Canada)

^c MCMASTER UNIVERSITY   (Canada)

Author keywords

Amyotrophic lateral sclerosis; Mitochondria; Nutrition; Oxidative stress; Physical activity; Superoxide Dismutase 1 (SOD1)

Indexed keywords

ACETYLCYSTEINE; ALPHA TOCOPHEROL; CARNITINE; CAROTENOID; CATALASE; CHELATING AGENT; CREATINE; CYANOCOBALAMIN; ENZYME; EPIGALLOCATECHIN GALLATE; FOLIC ACID; FREE RADICAL; GENISTEIN; GINKGO BILOBA EXTRACT; GINSENG EXTRACT; GLUTATHIONE PEROXIDASE; LEUCINE; LYCOPENE; MAGNESIUM; MELATONIN; PLACEBO; POLYPHENOL; PUTRESCINE MODIFIED CATALASE; PYRUVIC ACID; RILUZOLE; THIOCTIC ACID; THREONINE; UBIDECARENONE; UNCLASSIFIED DRUG; UNINDEXED DRUG; ZINC;

AMYOTROPHIC LATERAL SCLEROSIS; APOPTOSIS; CALORIC RESTRICTION; CLINICAL TRIAL; DIET THERAPY; EXCITOTOXICITY; GINKGO BILOBA; HUMAN; INFLAMMATION; KINESIOTHERAPY; MALNUTRITION; MITOCHONDRION; MOTONEURON; NONHUMAN; OUTCOME ASSESSMENT; PATHOGENESIS; PROTEIN AGGREGATION; PROTEIN FOLDING; RED WINE; REVIEW; ZINC DEFICIENCY;

AMYOTROPHIC LATERAL SCLEROSIS; ANIMALS; CLINICAL TRIALS AS TOPIC; EXERCISE; HUMANS; NUTRITIONAL STATUS; TREATMENT OUTCOME;

EID: 71549159146     PISSN: 02615614     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.clnu.2009.06.002     Document Type: Review

References (225)

1. Gonzalez de Aguilar J.L., Echaniz-Laguna A., Fergani A., Rene F., Meininger V., Loeffler J.P., et al. Amyotrophic lateral sclerosis: all roads lead to Rome. J Neurochem 101 5 (2007) 1153-1160
2. 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
3. Goodall E.F., and Morrison K.E. Amyotrophic lateral sclerosis (motor neuron disease): proposed mechanisms and pathways to treatment. Expert Rev Mol Med 8 11 (2006) 1-22
4. Delisle M.B., and Carpenter S. Neurofibrillary axonal swellings and amyotrophic lateral sclerosis. J Neurol Sci 63 2 (1984) 241-250
5. Eisen A. Amyotrophic lateral sclerosis: a 40-year personal perspective. J Clin Neurosci 16 4 (2009) 505-512
6. Rosen D.R., Siddique T., Patterson D., Figlewicz D.A., Sapp P., Hentati A., et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362 6415 (1993) 59-62
7. Deng H.X., Hentati A., Tainer J.A., Iqbal Z., Cayabyab A., Hung W.Y., et al. Amyotrophic lateral sclerosis and structural defects in Cu, Zn superoxide dismutase. Science 261 5124 (1993) 1047-1051
8. Borchelt D.R., Lee M.K., Slunt H.S., Guarnieri M., Xu Z.S., Wong P.C., et al. Superoxide dismutase 1 with mutations linked to familial amyotrophic lateral sclerosis possesses significant activity. Proc Natl Acad Sci U S A 91 17 (1994) 8292-8296
9. Crow J.P., Sampson J.B., Zhuang Y., Thompson J.A., and Beckman J.S. Decreased zinc affinity of amyotrophic lateral sclerosis-associated superoxide dismutase mutants leads to enhanced catalysis of tyrosine nitration by peroxynitrite. J Neurochem 69 5 (1997) 1936-1944
10. Higgins C.M., Jung C., Ding H., and XuMutant Cu Z. Zn superoxide dismutase that causes motoneuron degeneration is present in mitochondria in the CNS. J Neurosci 22 6 (2002) RC215
11. Jaarsma D., Rognoni F., van Duijn W., Verspaget H.W., Haasdijk E.D., and Holstege J.C. CuZn superoxide dismutase (SOD1) accumulates in vacuolated mitochondria in transgenic mice expressing amyotrophic lateral sclerosis-linked SOD1 mutations. Acta Neuropathol 102 4 (2001) 293-305
12. Mattiazzi M., D'Aurelio M., Gajewski C.D., Martushova K., Kiaei M., Beal M.F., et al. Mutated human SOD1 causes dysfunction of oxidative phosphorylation in mitochondria of transgenic mice. J Biol Chem 277 33 (2002) 29626-29633
13. Gurney M.E., Pu H., Chiu A.Y., Dal Canto M.C., Polchow C.Y., Alexander D.D., et al. Motor neuron degeneration in mice that express a human Cu, Zn superoxide dismutase mutation. Science 264 5166 (1994) 1772-1775
14. Borchelt D.R., Guarnieri M., Wong P.C., Lee M.K., Slunt H.S., Xu Z.S., et al. Superoxide dismutase 1 subunits with mutations linked to familial amyotrophic lateral sclerosis do not affect wild-type subunit function. J Biol Chem 270 7 (1995) 3234-3238
15. Ripps M.E., Huntley G.W., Hof P.R., Morrison J.H., and Gordon J.W. Transgenic mice expressing an altered murine superoxide dismutase gene provide an animal model of amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A 92 3 (1995) 689-693
16. Rabizadeh S., Gralla E.B., Borchelt D.R., Gwinn R., Valentine J.S., Sisodia S., et al. 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 U S A 92 7 (1995) 3024-3028
17. Bogdanov M.B., Ramos L.E., Xu Z., and Beal M.F. Elevated "hydroxyl radical" generation in vivo in an animal model of amyotrophic lateral sclerosis. J Neurochem 71 3 (1998) 1321-1324
18. Wiedau-Pazos M., Goto J.J., Rabizadeh S., Gralla E.B., Roe J.A., Lee M.K., et al. Altered reactivity of superoxide dismutase in familial amyotrophic lateral sclerosis. Science 271 5248 (1996) 515-518
19. Siddique T., and Deng H.X. Genetics of amyotrophic lateral sclerosis. Hum Mol Genet 5 Spec No (1996) 1465-1470
20. Yim M.B., Kang J.H., Yim H.S., Kwak H.S., Chock P.B., and Stadtman E.R. 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 U S A 93 12 (1996) 5709-5714
21. Hodgson E.K., and Fridovich I. The interaction of bovine erythrocyte superoxide dismutase with hydrogen peroxide: inactivation of the enzyme. Biochemistry 14 24 (1975) 5294-5299
22. Hall E.D., Andrus P.K., Oostveen J.A., Fleck T.J., and Gurney M.E. Relationship of oxygen radical-induced lipid peroxidative damage to disease onset and progression in a transgenic model of familial ALS. J Neurosci Res 53 1 (1998) 66-77
23. Beckman J.S., Carson M., Smith C.D., and Koppenol W.H. ALS, SOD and peroxynitrite. Nature 364 6438 (1993) 584
24. Bruijn L.I., Beal M.F., Becher M.W., Schulz J.B., Wong P.C., Price D.L., et al. 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 U S A 94 14 (1997) 7606-7611
25. Doucette P.A., Whitson L.J., Cao X., Schirf V., Demeler B., Valentine J.S., et al. Dissociation of human copper-zinc superoxide dismutase dimers using chaotrope and reductant. Insights into the molecular basis for dimer stability. J Biol Chem 279 52 (2004) 54558-54566
26. Takamiya R., Takahashi M., Park Y.S., Tawara Y., Fujiwara N., Miyamoto Y., et al. Overexpression of mutated Cu, Zn-SOD in neuroblastoma cells results in cytoskeletal change. Am J Physiol, Cell Physiol 288 2 (2005) C253-259
27. Ogawa Y., Kosaka H., Nakanishi T., Shimizu A., Ohoi N., Shouji H., et al. Stability of mutant superoxide dismutase-1 associated with familial amyotrophic lateral sclerosis determines the manner of copper release and induction of thioredoxin in erythrocytes. Biochem Biophys Res Commun 241 2 (1997) 251-257
28. Nagano S., Ogawa Y., Yanagihara T., and Sakoda S. Benefit of a combined treatment with trientine and ascorbate in familial amyotrophic lateral sclerosis model mice. Neurosci Lett 265 3 (1999) 159-162
29. Smith A.P., and Lee N.M. Role of zinc in ALS. Amyotroph Lateral Scler 8 3 (2007) 131-143
30. Beckman J.S., Beckman T.W., Chen J., Marshall P.A., and Freeman B.A. Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci U S A 87 4 (1990) 1620-1624
31. Bendotti C., and Carri M.T. Lessons from models of SOD1-linked familial ALS. Trends Mol Med 10 8 (2004) 393-400
32. Boillee S., Yamanaka K., Lobsiger C.S., Copeland N.G., Jenkins N.A., Kassiotis G., et al. Onset and progression in inherited ALS determined by motor neurons and microglia. Science 312 5778 (2006) 1389-1392
33. Pasinelli P., and Brown R.H. Molecular biology of amyotrophic lateral sclerosis: insights from genetics. Nat Rev Neurosci 7 9 (2006) 710-723
34. Brooks K.J., Hill M.D., Hockings P.D., and Reid D.G. MRI detects early hindlimb muscle atrophy in Gly93Ala superoxide dismutase-1 (G93A SOD1) transgenic mice, an animal model of familial amyotrophic lateral sclerosis. NMR Biomed 17 1 (2004) 28-32
35. Dupuis L., di Scala F., Rene F., de Tapia M., Oudart H., Pradat P.F., et al. Up-regulation of mitochondrial uncoupling protein 3 reveals an early muscular metabolic defect in amyotrophic lateral sclerosis. Faseb J 17 14 (2003) 2091-2093
36. Jokic N., Di Scala F., Dupuis L., Rene F., Muller A., Gonzalez De Aguilar J.L., et al. Early activation of antioxidant mechanisms in muscle of mutant Cu/Zn-superoxide dismutase-linked amyotrophic lateral sclerosis mice. Ann N Y Acad Sci 1010 (2003) 552-556
37. Leclerc N., Ribera F., Zoll J., Warter J.M., Poindron P., Lampert E., et al. Selective changes in mitochondria respiratory properties in oxidative or glycolytic muscle fibers isolated from G93AhumanSOD1 transgenic mice. Neuromuscul Disord 11 8 (2001) 722-727
38. Andrews Z.B., Diano S., and Horvath T.L. Mitochondrial uncoupling proteins in the CNS: in support of function and survival. Nat Rev Neurosci 6 11 (2005) 829-840
39. Doble A. The role of excitotoxicity in neurodegenerative disease: implications for therapy. Pharmacol Ther 81 3 (1999) 163-221
40. Rothstein J.D., Van Kammen M., Levey A.I., Martin L.J., and Kuncl R.W. Selective loss of glial glutamate transporter GLT-1 in amyotrophic lateral sclerosis. Ann Neurol 38 1 (1995) 73-84
41. Shaw P.J., Forrest V., Ince P.G., Richardson J.P., and Wastell H.J. CSF and plasma amino acid levels in motor neuron disease: elevation of CSF glutamate in a subset of patients. Neurodegeneration 4 2 (1995) 209-216
42. Spreux-Varoquaux O., Bensimon G., Lacomblez L., Salachas F., Pradat P.F., Le Forestier N., et al. Glutamate levels in cerebrospinal fluid in amyotrophic lateral sclerosis: a reappraisal using a new HPLC method with coulometric detection in a large cohort of patients. J Neurol Sci 193 2 (2002) 73-78
43. Van Den Bosch L., Van Damme P., Bogaert E., and Robberecht W. The role of excitotoxicity in the pathogenesis of amyotrophic lateral sclerosis. Biochim Biophys Acta 1762 11-12 (2006) 1068-1082
44. 2+ capacity impairment precedes the onset of motor symptoms in G93A Cu/Zn-superoxide dismutase mutant mice. J Neurochem 96 5 (2006) 1349-1361
45. Choi D.W. Ionic dependence of glutamate neurotoxicity. J Neurosci 7 2 (1987) 369-379
46. Roy J., Minotti S., Dong L., Figlewicz D.A., and Durham H.D. Glutamate potentiates the toxicity of mutant Cu/Zn-superoxide dismutase in motor neurons by postsynaptic calcium-dependent mechanisms. J Neurosci 18 23 (1998) 9673-9684
47. Chiu A.Y., Zhai P., Dal Canto M.C., Peters T.M., Kwon Y.W., Prattis S.M., et al. Age-dependent penetrance of disease in a transgenic mouse model of familial amyotrophic lateral sclerosis. Mol Cell Neurosci 6 4 (1995) 349-362
48. Wong P.C., Pardo C.A., Borchelt D.R., Lee M.K., Copeland N.G., Jenkins N.A., et al. An adverse property of a familial ALS-linked SOD1 mutation causes motor neuron disease characterized by vacuolar degeneration of mitochondria. Neuron 14 6 (1995) 1105-1116
49. Vijayvergiya C., Beal M.F., Buck J., and Manfredi G. Mutant superoxide dismutase 1 forms aggregates in the brain mitochondrial matrix of amyotrophic lateral sclerosis mice. J Neurosci 25 10 (2005) 2463-2470
50. Higgins C.M., Jung C., and Xu Z. ALS-associated mutant SOD1G93A causes mitochondrial vacuolation by expansion of the intermembrane space and by involvement of SOD1 aggregation and peroxisomes. BMC Neurosci 4 (2003) 16
51. Liu J., Lillo C., Jonsson P.A., Vande Velde C., Ward C.M., Miller T.M., et al. Toxicity of familial ALS-linked SOD1 mutants from selective recruitment to spinal mitochondria. Neuron 43 1 (2004) 5-17
52. Pasinelli P., Belford M.E., Lennon N., Bacskai B.J., Hyman B.T., Trotti D., et al. Amyotrophic lateral sclerosis-associated SOD1 mutant proteins bind and aggregate with Bcl-2 in spinal cord mitochondria. Neuron 43 1 (2004) 19-30
53. Takeuchi H., Kobayashi Y., Ishigaki S., Doyu M., and Sobue G. Mitochondrial localization of mutant superoxide dismutase 1 triggers caspase-dependent cell death in a cellular model of familial amyotrophic lateral sclerosis. J Biol Chem 277 52 (2002) 50966-50972
54. Hensley K., Mhatre M., Mou S., Pye Q.N., Stewart C., West M., et al. On the relation of oxidative stress to neuroinflammation: lessons learned from the G93A-SOD1 mouse model of amyotrophic lateral sclerosis. Antioxid Redox Signal 8 11-12 (2006) 2075-2087
55. Venters H.D., Dantzer R., and Kelley K.W. A new concept in neurodegeneration: TNFalpha is a silencer of survival signals. Trends Neurosci 23 4 (2000) 175-180
56. Hensley K., Fedynyshyn J., Ferrell S., Floyd R.A., Gordon B., Grammas P., et al. Message and protein-level elevation of tumor necrosis factor alpha (TNF alpha) and TNF alpha-modulating cytokines in spinal cords of the G93A-SOD1 mouse model for amyotrophic lateral sclerosis. Neurobiol Dis 14 1 (2003) 74-80
57. Yoshihara T., Ishigaki S., Yamamoto M., Liang Y., Niwa J., Takeuchi H., et al. 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 1 (2002) 158-167
58. Poloni M., Facchetti D., Mai R., Micheli A., Agnoletti L., Francolini G., et al. Circulating levels of tumour necrosis factor-alpha and its soluble receptors are increased in the blood of patients with amyotrophic lateral sclerosis. Neurosci Lett 287 3 (2000) 211-214
59. Kiaei M., Petri S., Kipiani K., Gardian G., Choi D.K., Chen J., et al. Thalidomide and lenalidomide extend survival in a transgenic mouse model of amyotrophic lateral sclerosis. J Neurosci 26 9 (2006) 2467-2473
60. Sathasivam S., and Shaw P.J. Apoptosis in amyotrophic lateral sclerosis-what is the evidence?. Lancet Neurol 4 8 (2005) 500-509
61. Ascherio A., Weisskopf M.G., O'Reilly E.J., Jacobs E.J., McCullough M.L., Calle E.E., et al. Vitamin E intake and risk of amyotrophic lateral sclerosis. Ann Neurol 57 1 (2005) 104-110
62. Esposito E., Rotilio D., Di Matteo V., Di Giulio C., Cacchio M., and Algeri S. A review of specific dietary antioxidants and the effects on biochemical mechanisms related to neurodegenerative processes. Neurobiol Aging 23 5 (2002) 719-735
63. Gurney M.E., Cutting F.B., Zhai P., Doble A., Taylor C.P., Andrus P.K., et al. Benefit of vitamin E, riluzole, and gabapentin in a transgenic model of familial amyotrophic lateral sclerosis. Ann Neurol 39 2 (1996) 147-157
64. Desnuelle C., Dib M., Garrel C., and Favier A. A double-blind, placebo-controlled randomized clinical trial of alpha-tocopherol (vitamin E) in the treatment of amyotrophic lateral sclerosis. ALS riluzole-tocopherol Study Group. Amyotroph Lateral Scler Other Motor Neuron Disord 2 1 (2001) 9-18
65. Graf M., Ecker D., Horowski R., Kramer B., Riederer P., Gerlach M., et al. High dose vitamin E therapy in amyotrophic lateral sclerosis as add-on therapy to riluzole: results of a placebo-controlled double-blind study. J Neural Transm 112 5 (2005) 649-660
66. Galbussera A., Tremolizzo L., Brighina L., Testa D., Lovati R., Ferrarese C., et al. Vitamin E intake and quality of life in amyotrophic lateral sclerosis patients: a follow-up case series study. Neurol Sci 27 3 (2006) 190-193
67. Veldink J.H., Kalmijn S., Groeneveld G.J., Wunderink W., Koster A., de Vries J.H., et al. Intake of polyunsaturated fatty acids and vitamin E reduces the risk of developing amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatr 78 4 (2007) 367-371
68. Mattson M.P., and Shea T.B. Folate and homocysteine metabolism in neural plasticity and neurodegenerative disorders. Trends Neurosci 26 3 (2003) 137-146
69. Zoccolella S., Simone I.L., Lamberti P., Samarelli V., Tortelli R., Serlenga L., et al. Elevated plasma homocysteine levels in patients with amyotrophic lateral sclerosis. Neurology 70 3 (2008) 222-225
70. Diaz-Arrastia R. Homocysteine and neurologic disease. Arch Neurol 57 10 (2000) 1422-1427
71. Carmel R., Green R., Rosenblatt D.S., and Watkins D. Update on cobalamin, folate, and homocysteine. Hematology Am Soc Hematol Educ Program (2003) 62-81
72. Zhang X., Chen S., Li L., Wang Q., and Le W. Folic acid protects motor neurons against the increased homocysteine, inflammation and apoptosis in SOD1 (G93A) transgenic mice. Neuropharmacology 54 7 (2008) 1112-1119
73. Blomgren K., and Hagberg H. Free radicals, mitochondria, and hypoxia-ischemia in the developing brain. Free Radic Biol Med 40 3 (2006) 388-397
74. Mittal C.K. Nitric oxide synthase: involvement of oxygen radicals in conversion of l-arginine to nitric oxide. Biochem Biophys Res Commun 193 1 (1993) 126-132
75. Wengenack T.M., Curran G.L., Olson E.E., and Poduslo J.F. Putrescine-modified catalase with preserved enzymatic activity exhibits increased permeability at the blood-nerve and blood-brain barriers. Brain Res. 767 1 (1997) 128-135
76. Reinholz M.M., Haggard J.J., Curran G.L., and Poduslo J.F. Plasma pharmacokinetics, nervous system biodistribution and biostability, and spinal cord permeability at the blood-brain barrier of putrescine-modified catalase in the adult rat. Exp Neurol 159 1 (1999) 191-203
77. Reinholz M.M., Merkle C.M., and Poduslo J.F. Therapeutic benefits of putrescine-modified catalase in a transgenic mouse model of familial amyotrophic lateral sclerosis. Exp Neurol 159 1 (1999) 204-216
78. Poduslo J.F., Whelan S.L., Curran G.L., and Wengenack T.M. Therapeutic benefit of polyamine-modified catalase as a scavenger of hydrogen peroxide and nitric oxide in familial amyotrophic lateral sclerosis transgenics. Ann Neurol 48 6 (2000) 943-947
79. Chio A., Cucatto A., Terreni A.A., and Schiffer D. Reduced glutathione in amyotrophic lateral sclerosis: an open, crossover, randomized trial. Ital J Neurol Sci 19 6 (1998) 363-366
80. Kannan R., Kuhlenkamp J.F., Jeandidier E., Trinh H., Ookhtens M., and Kaplowitz N. Evidence for carrier-mediated transport of glutathione across the blood-brain barrier in the rat. J Clin Invest 85 6 (1990) 2009-2013
81. Abe M., Takiguchi Y., Ichimaru S., Tsuchiya K., and Wada K. Comparison of the protective effect of N-acetylcysteine by different treatments on rat myocardial ischemia-reperfusion injury. J Pharmacol Sci (2008)
82. Louwerse E.S., Weverling G.J., Bossuyt P.M., Meyjes F.E., and de Jong J.M. Randomized, double-blind, controlled trial of acetylcysteine in amyotrophic lateral sclerosis. Arch Neurol 52 6 (1995) 559-564
83. Jaarsma D., Guchelaar H.J., Haasdijk E., de Jong J.M., and Holstege J.C. The antioxidant N-acetylcysteine does not delay disease onset and death in a transgenic mouse model of amyotrophic lateral sclerosis. Ann Neurol 44 2 (1998) 293
84. Andreassen O.A., Dedeoglu A., Klivenyi P., Beal M.F., and Bush A.I. N-acetyl-l-cysteine improves survival and preserves motor performance in an animal model of familial amyotrophic lateral sclerosis. Neuroreport 11 11 (2000) 2491-2493
85. Packer L., Kraemer K., and Rimbach G. Molecular aspects of lipoic acid in the prevention of diabetes complications. Nutrition 17 10 (2001) 888-895
86. Arivazhagan P., Ramanathan K., and Panneerselvam C. Effect of DL-alpha-lipoic acid on the status of lipid peroxidation and antioxidants in mitochondria of aged rats. J Nutr Biochem 12 1 (2001) 2-6
87. Andreassen O.A., Dedeoglu A., Friedlich A., Ferrante K.L., Hughes D., Szabo C., et al. Effects of an inhibitor of poly(ADP-ribose) polymerase, desmethylselegiline, trientine, and lipoic acid in transgenic ALS mice. Exp Neurol 168 2 (2001) 419-424
88. Marangon K., Devaraj S., Tirosh O., Packer L., and Jialal I. Comparison of the effect of alpha-lipoic acid and alpha-tocopherol supplementation on measures of oxidative stress. Free Radic Biol Med 27 9-10 (1999) 1114-1121
89. Amodio R., Esposito E., De Ruvo C., Bellavia V., Amodio E., and Carruba G. Red wine extract prevents neuronal apoptosis in vitro and reduces mortality of transgenic mice. Ann N Y Acad Sci 1089 (2006) 88-97
90. Esposito E., Rossi C., Amodio R., Di Castelnuovo A., Bendotti C., Rotondo T., et al. Lyophilized red wine administration prolongs survival in an animal model of amyotrophic lateral sclerosis. Ann Neurol 48 4 (2000) 686-687
91. De Ruvo C., Amodio R., Algeri S., Martelli N., Intilangelo A., D'Ancona G.M., et al. Nutritional antioxidants as antidegenerative agents. Int J Dev Neurosci 18 4-5 (2000) 359-366
92. Ferrante K.L., Shefner J., Zhang H., Betensky R., O'Brien M., Yu H., et al. Tolerance of high-dose (3000 mg/day) coenzyme Q10 in ALS. Neurology 65 11 (2005) 1834-1836
93. Noack H., Kube U., and Augustin W. Relations between tocopherol depletion and coenzyme Q during lipid peroxidation in rat liver mitochondria. Free Radic Res 20 6 (1994) 375-386
94. Beal M.F. Coenzyme Q10 as a possible treatment for neurodegenerative diseases. Free Radic Res 36 4 (2002) 455-460
95. Matthews R.T., Yang L., Browne S., Baik M., and Beal M.F. Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects. Proc Natl Acad Sci U S A 95 15 (1998) 8892-8897
96. Favit A., Nicoletti F., Scapagnini U., and Canonico P.L. Ubiquinone protects cultured neurons against spontaneous and excitotoxin-induced degeneration. J Cereb Blood Flow Metab 12 4 (1992) 638-645
97. Koh S.H., Lee S.M., Kim H.Y., Lee K.Y., Lee Y.J., Kim H.T., et al. The effect of epigallocatechin gallate on suppressing disease progression of ALS model mice. Neurosci Lett 395 2 (2006) 103-107
98. Khan S.A., Priyamvada S., Arivarasu N.A., Khan S., and Yusufi A.N. Influence of green tea on enzymes of carbohydrate metabolism, antioxidant defense, and plasma membrane in rat tissues. Nutrition 23 9 (2007) 687-695
99. Xu Z., Chen S., Li X., Luo G., Li L., and Le W. Neuroprotective effects of (-)-epigallocatechin-3-gallate in a transgenic mouse model of amyotrophic lateral sclerosis. Neurochem Res 31 10 (2006) 1263-1269
100. Jiang F., DeSilva S., and Turnbull J. Beneficial effect of ginseng root in SOD-1 (G93A) transgenic mice. J Neurol Sci 180 1-2 (2000) 52-54
101. Chen Q.S. [Pharmacological studies on notoginseng saponins isolated from the fibrous root of Panax notoginseng]. Zhong Yao Tong Bao 12 3 (1987) 45-47
102. Lim J.H., Wen T.C., Matsuda S., Tanaka J., Maeda N., Peng H., et al. Protection of ischemic hippocampal neurons by ginsenoside Rb1, a main ingredient of ginseng root. Neurosci Res 28 3 (1997) 191-200
103. Gillis C.N. Panax ginseng pharmacology: a nitric oxide link?. Biochem Pharmacol 54 1 (1997) 1-8
104. 2+ channels in vascular smooth muscle. Zhongguo Yao Li Xue Bao 15 5 (1994) 392-398
105. Braquet P., and Hosford D. Ethnopharmacology and the development of natural PAF antagonists as therapeutic agents. J Ethnopharmacol 32 1-3 (1991) 135-139
106. Bastianetto S., Zheng W.H., and Quirion R. The Ginkgo biloba extract (EGb 761) protects and rescues hippocampal cells against nitric oxide-induced toxicity: involvement of its flavonoid constituents and protein kinase C. J Neurochem 74 6 (2000) 2268-2277
107. Sastre J., Millan A., Garcia de la Asuncion J., Pla R., Juan G., Pallardo, et al. A Ginkgo biloba extract (EGb 761) prevents mitochondrial aging by protecting against oxidative stress. Free Radic Biol Med 24 2 (1998) 298-304
108. Ferrante R.J., Klein A.M., Dedeoglu A., and Beal M.F. Therapeutic efficacy of EGb761 (Gingko biloba extract) in a transgenic mouse model of amyotrophic lateral sclerosis. J Mol Neurosci 17 1 (2001) 89-96
109. Esposito E., Capasso M., di Tomasso N., Corona C., Pellegrini F., Uncini A., et al. Antioxidant strategies based on tomato-enriched food or pyruvate do not affect disease onset and survival in an animal model of amyotrophic lateral sclerosis. Brain Res (2007)
110. Hamadeh M.J., Rodriguez M.C., Kaczor J.J., and Tarnopolsky M.A. Caloric restriction transiently improves motor performance but hastens clinical onset of disease in the Cu/Zn-superoxide dismutase mutant G93A mouse. Muscle Nerve 31 2 (2005) 214-220
111. Gurney M.E. The use of transgenic mouse models of amyotrophic lateral sclerosis in preclinical drug studies. J Neurol Sci 152 Suppl. 1 (1997) S67-73
112. Bremer J. Carnitine-metabolism and functions. Physiol Rev 63 4 (1983) 1420-1480
113. Hagen T.M., Liu J., Lykkesfeldt J., Wehr C.M., Ingersoll R.T., Vinarsky V., et al. Feeding acetyl-l-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress. Proc Natl Acad Sci U S A 99 4 (2002) 1870-1875
114. Pastorino J.G., Snyder J.W., Serroni A., Hoek J.B., and Farber J.L. Cyclosporin and carnitine prevent the anoxic death of cultured hepatocytes by inhibiting the mitochondrial permeability transition. J Biol Chem 268 19 (1993) 13791-13798
115. Therrien G., Rose C., Butterworth J., and Butterworth R.F. Protective effect of l-carnitine in ammonia-precipitated encephalopathy in the portacaval shunted rat. Hepatology 25 3 (1997) 551-556
116. Farooqui A.A., Yang H.C., Rosenberger T.A., and Horrocks L.A. Phospholipase A2 and its role in brain tissue. J Neurochem 69 3 (1997) 889-901
117. Kim J.S., He L., and Lemasters J.J. Mitochondrial permeability transition: a common pathway to necrosis and apoptosis. Biochem Biophys Res Commun 304 3 (2003) 463-470
118. Kira Y., Nishikawa M., Ochi A., Sato E., and Inoue M. L-carnitine suppresses the onset of neuromuscular degeneration and increases the life span of mice with familial amyotrophic lateral sclerosis. Brain Res. 1070 1 (2006) 206-214
119. Choi C.I., Lee Y.D., Gwag B.J., Cho S.I., Kim S.S., and Suh-Kim H. Effects of estrogen on lifespan and motor functions in female hSOD1 G93A transgenic mice. J Neurol Sci 268 1-2 (2008) 40-47
120. Santell R.C., Chang Y.C., Nair M.G., and Helferich W.G. Dietary genistein exerts estrogenic effects upon the uterus, mammary gland and the hypothalamic/pituitary axis in rats. J Nutr 127 2 (1997) 263-269
121. Hilakivi-Clarke L., Cho E., and Clarke R. Maternal genistein exposure mimics the effects of estrogen on mammary gland development in female mouse offspring. Oncol Rep 5 3 (1998) 609-616
122. Zava D.T., Blen M., and Duwe G. Estrogenic activity of natural and synthetic estrogens in human breast cancer cells in culture. Environ Health Perspect 105 Suppl. 3 (1997) 637-645
123. Trieu V.N., and Uckun F.M. Genistein is neuroprotective in murine models of familial amyotrophic lateral sclerosis and stroke. Biochem Biophys Res Commun 258 3 (1999) 685-688
124. Pardridge W.M., and Mietus L.J. Transport of albumin-bound melatonin through the blood-brain barrier. J Neurochem 34 6 (1980) 1761-1763
125. Tan D.X., Reiter R.J., Manchester L.C., Yan M.T., El-Sawi M., Sainz R.M., et al. Chemical and physical properties and potential mechanisms: melatonin as a broad spectrum antioxidant and free radical scavenger. Curr Top Med Chem 2 2 (2002) 181-197
126. Reiter R.J. Oxidative damage in the central nervous system: protection by melatonin. Prog Neurobiol 56 3 (1998) 359-384
127. Weishaupt J.H., Bartels C., Polking E., Dietrich J., Rohde G., Poeggeler B., et al. Reduced oxidative damage in ALS by high-dose enteral melatonin treatment. J Pineal Res 41 4 (2006) 313-323
128. Barja G., Cadenas S., Rojas C., Lopez-Torres M., and Perez-Campo R. A decrease of free radical production near critical targets as a cause of maximum longevity in animals. Comp Biochem Physiol Biochem Mol Biol 108 4 (1994) 501-512
129. Gredilla R., Sanz A., Lopez-Torres M., and Barja G. Caloric restriction decreases mitochondrial free radical generation at complex I and lowers oxidative damage to mitochondrial DNA in the rat heart. Faseb J 15 9 (2001) 1589-1591
130. Judge S., Judge A., Grune T., and Leeuwenburgh C. Short-term CR decreases cardiac mitochondrial oxidant production but increases carbonyl content. Am J Physiol Regul Integr Comp Physiol 286 2 (2004) R254-259
131. Mair W., Goymer P., Pletcher S.D., and Partridge L. Demography of dietary restriction and death in Drosophila. Science 301 5640 (2003) 1731-1733
132. Ramsey J.J., Harper M.E., and Weindruch R. Restriction of energy intake, energy expenditure, and aging. Free Radic Biol Med 29 10 (2000) 946-968
133. Armeni T., Principato G., Quiles J.L., Pieri C., Bompadre S., and Battino M. Mitochondrial dysfunctions during aging: vitamin E deficiency or caloric restriction-two different ways of modulating stress. J Bioenerg Biomembr 35 2 (2003) 181-191
134. Selman C., Grune T., Stolzing A., Jakstadt M., McLaren J.S., and Speakman J.R. The consequences of acute cold exposure on protein oxidation and proteasome activity in short-tailed field voles, Microtus agrestis. Free Radic Biol Med 33 2 (2002) 259-265
135. Selman C., Phillips T., Staib J.L., Duncan J.S., Leeuwenburgh C., and Speakman J.R. Energy expenditure of calorically restricted rats is higher than predicted from their altered body composition. Mech Ageing Dev 126 6-7 (2005) 783-793
136. Hunt N.D., Hyun D.H., Allard J.S., Minor R.K., Mattson M.P., Ingram D.K., et al. Bioenergetics of aging and calorie restriction. Ageing Res Rev 5 2 (2006) 125-143
137. Cameron A., and Rosenfeld J. Nutritional issues and supplements in amyotrophic lateral sclerosis and other neurodegenerative disorders. Curr Opin Clin Nutr Metab Care 5 6 (2002) 631-643
138. Kasarskis E.J., Berryman S., Vanderleest J.G., Schneider A.R., and McClain C.J. Nutritional status of patients with amyotrophic lateral sclerosis: relation to the proximity of death. Am J Clin Nutr 63 1 (1996) 130-137
139. Aldrich T.K. Nutritional factors in the pathogenesis and therapy of respiratory insufficiency in neuromuscular diseases. Monaldi Arch Chest Dis 48 4 (1993) 327-330
140. Slowie L.A., Paige M.S., and Antel J.P. Nutritional considerations in the management of patients with amyotrophic lateral sclerosis (ALS). J Am Diet Assoc 83 1 (1983) 44-47
141. Rio A., and Cawadias E. Nutritional advice and treatment by dietitians to patients with amyotrophic lateral sclerosis/motor neurone disease: a survey of current practice in England, Wales, Northern Ireland and Canada. J Hum Nutr Diet 20 1 (2007) 3-13
142. Hamadeh M.J., and Tarnopolsky M.A. Transient caloric restriction in early adulthood hastens disease endpoint in male, but not female, Cu/Zn-SOD mutant G93A mice. Muscle Nerve 34 6 (2006) 709-719
143. Pedersen W.A., and Mattson M.P. No benefit of dietary restriction on disease onset or progression in amyotrophic lateral sclerosis Cu/Zn-superoxide dismutase mutant mice. Brain Res 833 1 (1999) 117-120
144. Delanty N., Reilly M.P., Pratico D., Lawson J.A., McCarthy J.F., Wood A.E., et al. 8-epi PGF2 alpha generation during coronary reperfusion. A potential quantitative marker of oxidant stress in vivo. Circulation 95 11 (1997) 2492-2499
145. Kawasaki S., Sugiyama S., Ishiguro N., Ozawa T., and Miura T. Implication of superoxide radicals on ischemia-reperfusion-induced skeletal muscle injury in rats. Eur Surg Res 25 3 (1993) 129-136
146. Reilly M.P., Delanty N., Roy L., Rokach J., Callaghan P.O., Crean P., et al. Increased formation of the isoprostanes IPF2alpha-I and 8-epi-prostaglandin F2alpha in acute coronary angioplasty: evidence for oxidant stress during coronary reperfusion in humans. Circulation 96 10 (1997) 3314-3320
147. Zhao Z., Lange D.J., Voustianiouk A., MacGrogan D., Ho L., Suh J., et al. A ketogenic diet as a potential novel therapeutic intervention in amyotrophic lateral sclerosis. BMC Neurosci 7 (2006) 29
148. Dupuis L., Oudart H., Rene F., Gonzalez de Aguilar J.L., and Loeffler J.P. Evidence for defective energy homeostasis in amyotrophic lateral sclerosis: benefit of a high-energy diet in a transgenic mouse model. Proc Natl Acad Sci U S A 101 30 (2004) 11159-11164
149. Mattson M.P., Cutler R.G., and Camandola S. Energy intake and amyotrophic lateral sclerosis. Neuromolecular Med 9 1 (2007) 17-20
150. Desport J.C., Preux P.M., Truong T.C., Vallat J.M., Sautereau D., and Couratier P. Nutritional status is a prognostic factor for survival in ALS patients. Neurology 53 5 (1999) 1059-1063
151. Gunther M.R., Hanna P.M., Mason R.P., and Cohen M.S. Hydroxyl radical formation from cuprous ion and hydrogen peroxide: a spin-trapping study. Arch Biochem Biophys 316 1 (1995) 515-522
152. Avshalumov M.V., Chen B.T., and Rice M.E. Mechanisms underlying H(2)O(2)-mediated inhibition of synaptic transmission in rat hippocampal slices. Brain Res 882 1-2 (2000) 86-94
153. Hottinger A.F., Fine E.G., Gurney M.E., Zurn A.D., and Aebischer P. 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 7 (1997) 1548-1551
154. Nagano S., Fujii Y., Yamamoto T., Taniyama M., Fukada K., Yanagihara T., et al. The efficacy of trientine or ascorbate alone compared to that of the combined treatment with these two agents in familial amyotrophic lateral sclerosis model mice. Exp Neurol 179 2 (2003) 176-180
155. Ermilova I.P., Ermilov V.B., Levy M., Ho E., Pereira C., and Beckman J.S. Protection by dietary zinc in ALS mutant G93A SOD transgenic mice. Neurosci Lett 379 1 (2005) 42-46
156. Groeneveld G.J., de Leeuw van Weenen J., van Muiswinkel F.L., Veldman H., Veldink J.H., Wokke J.H., et al. Zinc amplifies mSOD1-mediated toxicity in a transgenic mouse model of amyotrophic lateral sclerosis. Neurosci Lett 352 3 (2003) 175-178
157. Fox P.L. The copper-iron chronicles: the story of an intimate relationship. Biometals 16 1 (2003) 9-40
158. Klivenyi P., Ferrante R.J., Matthews R.T., Bogdanov M.B., Klein A.M., Andreassen O.A., et al. Neuroprotective effects of creatine in a transgenic animal model of amyotrophic lateral sclerosis. Nat Med 5 3 (1999) 347-350
159. Matthews R.T., Yang L., Jenkins B.G., Ferrante R.J., Rosen B.R., Kaddurah-Daouk R., et al. Neuroprotective effects of creatine and cyclocreatine in animal models of Huntington's disease. J Neurosci 18 1 (1998) 156-163
160. O'Gorman E., Beutner G., Wallimann T., and Brdiczka D. Differential effects of creatine depletion on the regulation of enzyme activities and on creatine-stimulated mitochondrial respiration in skeletal muscle, heart, and brain. Biochim Biophys Acta 1276 2 (1996) 161-170
161. Xu C.J., Klunk W.E., Kanfer J.N., Xiong Q., Miller G., and Pettegrew J.W. Phosphocreatine-dependent glutamate uptake by synaptic vesicles. A comparison with atp-dependent glutamate uptake. J Biol Chem 271 23 (1996) 13435-13440
162. Saks V.A., Kongas O., Vendelin M., and Kay L. Role of the creatine/phosphocreatine system in the regulation of mitochondrial respiration. Acta Physiol Scand 168 4 (2000) 635-641
163. Andreassen O.A., Jenkins B.G., Dedeoglu A., Ferrante K.L., Bogdanov M.B., Kaddurah-Daouk R., et al. Increases in cortical glutamate concentrations in transgenic amyotrophic lateral sclerosis mice are attenuated by creatine supplementation. J Neurochem 77 2 (2001) 383-390
164. Derave W., Van Den Bosch L., Lemmens G., Eijnde B.O., Robberecht W., and Hespel P. Skeletal muscle properties in a transgenic mouse model for amyotrophic lateral sclerosis: effects of creatine treatment. Neurobiol Dis 13 3 (2003) 264-272
165. Snow R.J., Turnbull J., da Silva S., Jiang F., and Tarnopolsky M.A. Creatine supplementation and riluzole treatment provide similar beneficial effects in copper, zinc superoxide dismutase (G93A) transgenic mice. Neuroscience 119 3 (2003) 661-667
166. Groeneveld G.J., Veldink J.H., van der Tweel I., Kalmijn S., Beijer C., de Visser M., et al. A randomized sequential trial of creatine in amyotrophic lateral sclerosis. Ann Neurol 53 4 (2003) 437-445
167. Mazzini L., Balzarini C., Colombo R., Mora G., Pastore I., De Ambrogio R., et al. Effects of creatine supplementation on exercise performance and muscular strength in amyotrophic lateral sclerosis: preliminary results. J Neurol Sci 191 1-2 (2001) 139-144
168. Shefner J.M., Cudkowicz M.E., Schoenfeld D., Conrad T., Taft J., Chilton M., et al. A clinical trial of creatine in ALS. Neurology 63 9 (2004) 1656-1661
169. Rosenfeld J., King R.M., Jackson C.E., Bedlack R.S., Barohn R.J., Dick A., et al. Creatine monohydrate in ALS: effects on strength, fatigue, respiratory status and ALSFRS. Amyotroph Lateral Scler 9 5 (2008) 266-272
170. Tsacopoulos M., and Magistretti P.J. Metabolic coupling between glia and neurons. J Neurosci 16 3 (1996) 877-885
171. Giandomenico A.R., Cerniglia G.E., Biaglow J.E., Stevens C.W., and Koch C.J. The importance of sodium pyruvate in assessing damage produced by hydrogen peroxide. Free Radic Biol Med 23 3 (1997) 426-434
172. Desagher S., Glowinski J., and Premont J. Pyruvate protects neurons against hydrogen peroxide-induced toxicity. J Neurosci 17 23 (1997) 9060-9067
173. Wang X.F., and Cynader M.S. Pyruvate released by astrocytes protects neurons from copper-catalyzed cysteine neurotoxicity. J Neurosci 21 10 (2001) 3322-3331
174. Park J.H., Hong Y.H., Kim H.J., Kim S.M., Kim M.J., Park K.S., et al. Pyruvate slows disease progression in a G93A SOD1 mutant transgenic mouse model. Neurosci Lett 413 3 (2007) 265-269
175. Tretter L., Liktor B., and Adam-Vizi V. Dual effect of pyruvate in isolated nerve terminals: generation of reactive oxygen species and protection of aconitase. Neurochem Res 30 10 (2005) 1331-1338
176. Heiman-Patterson T.D., Deitch J.S., Blankenhorn E.P., Erwin K.L., Perreault M.J., Alexander B.K., et al. Background and gender effects on survival in the TgN(SOD1-G93A)1Gur mouse model of ALS. J Neurol Sci 236 1-2 (2005) 1-7
177. Gredal O., and Moller S.E. Effect of branched-chain amino acids on glutamate metabolism in amyotrophic lateral sclerosis. J Neurol Sci 129 1 (1995) 40-43
178. Yielding K.L., and Tomkins G.M. An effect of l-leucine and other essential amino acids on the structure and activity of glutamic dehydrogenase. Proc Natl Acad Sci U S A 47 (1961) 983-989
179. Plaitakis A., Smith J., Mandeli J., and Yahr M.D. Pilot trial of branched-chain aminoacids in amyotrophic lateral sclerosis. Lancet 1 8593 (1988) 1015-1018
180. Testa D., Caraceni T., and Fetoni V. Branched-chain amino acids in the treatment of amyotrophic lateral sclerosis. J Neurol 236 8 (1989) 445-447
181. The Italian ALS Study Group. Branched-chain amino acids and amyotrophic lateral sclerosis: a treatment failure? The Italian ALS Study Group. Neurology 43 12 (1993) 2466-2470
182. Bastone A., Micheli A., Beghi E., and Salmona M. The imbalance of brain large-chain aminoacid availability in amyotrophic lateral sclerosis patients treated with high doses of branched-chain aminoacids. Neurochem Int 27 6 (1995) 467-472
183. Curtis D.R., Hosli L., Johnston G.A., and Johnston I.H. The hyperpolarization of spinal motoneurones by glycine and related amino acids. Exp Brain Res 5 3 (1968) 235-258
184. Tandan R., Bromberg M.B., Forshew D., Fries T.J., Badger G.J., Carpenter J., et al. A controlled trial of amino acid therapy in amyotrophic lateral sclerosis: I. Clinical, functional, and maximum isometric torque data. Neurology 47 5 (1996) 1220-1226
185. Testa D., Caraceni T., Fetoni V., and Girotti F. Chronic treatment with l-threonine in amyotrophic lateral sclerosis: a pilot study. Clin Neurol Neurosurg 94 1 (1992) 7-9
186. Blin O., Pouget J., Aubrespy G., Guelton C., Crevat A., and Serratrice G. A double-blind placebo-controlled trial of l-threonine in amyotrophic lateral sclerosis. J Neurol 239 2 (1992) 79-81
187. Hallak M., Martinez-Poyer J., Kruger M.L., Hassan S., Blackwell S.C., and Sorokin Y. The effect of magnesium sulfate on fetal heart rate parameters: a randomized, placebo-controlled trial. Am J Obstet Gynecol 181 5 Pt 1 (1999) 1122-1127
188. Iseri L.T., and French J.H. Magnesium: nature's physiologic calcium blocker. Am Heart J 108 1 (1984) 188-193
189. Lin J.Y., Chung S.Y., Lin M.C., and Cheng F.C. Effects of magnesium sulfate on energy metabolites and glutamate in the cortex during focal cerebral ischemia and reperfusion in the gerbil monitored by a dual-probe microdialysis technique. Life Sci 71 7 (2002) 803-811
190. Pamphlett R., Todd E., Vink R., McQuilty R., and Cheema S.S. Magnesium supplementation does not delay disease onset or increase survival in a mouse model of familial ALS. J Neurol Sci 216 1 (2003) 95-98
191. Heath P.R., and Shaw P.J. Update on the glutamatergic neurotransmitter system and the role of excitotoxicity in amyotrophic lateral sclerosis. Muscle Nerve 26 4 (2002) 438-458
192. 2+ permeable AMPA or kainate receptors: possible key factors in selective neurodegeneration. Trends Neurosci 23 8 (2000) 365-371
193. Apostolski S., Marinkovic Z., Nikolic A., Blagojevic D., Spasic M.B., and Michelson A.M. Glutathione peroxidase in amyotrophic lateral sclerosis: the effects of selenium supplementation. J Environ Pathol Toxicol Oncol 17 3-4 (1998) 325-329
194. Orrell R.W., Lane R.J., and Ross M. Antioxidant treatment for amyotrophic lateral sclerosis/motor neuron disease. Cochrane Database Syst Rev 1 (2007) CD002829
195. Drory V.E., Goltsman E., Reznik J.G., Mosek A., and Korczyn A.D. The value of muscle exercise in patients with amyotrophic lateral sclerosis. J Neurol Sci 191 1-2 (2001) 133-137
196. Scarmeas N., Shih T., Stern Y., Ottman R., and Rowland L.P. Premorbid weight, body mass, and varsity athletics in ALS. Neurology 59 5 (2002) 773-775
197. Strickland D., Smith S.A., Dolliff G., Goldman L., and Roelofs R.I. Physical activity, trauma, and ALS: a case-control study. Acta Neurol Scand 94 1 (1996) 45-50
198. Liebetanz D., Hagemann K., von Lewinski F., Kahler E., and Paulus W. Extensive exercise is not harmful in amyotrophic lateral sclerosis. Eur J Neurosci 20 11 (2004) 3115-3120
199. Itoh H., Ohkuwa T., Yamamoto T., Sato Y., Miyamura M., and Naoi M. Effects of endurance physical training on hydroxyl radical generation in rat tissues. Life Sci 63 21 (1998) 1921-1929
200. Siciliano G., Pastorini E., Pasquali L., Manca M.L., Iudice A., and Murri L. Impaired oxidative metabolism in exercising muscle from ALS patients. J Neurol Sci 191 1-2 (2001) 61-65
201. Siciliano G., D'Avino C., Del Corona A., Barsacchi R., Kusmic C., Rocchi A., et al. Impaired oxidative metabolism and lipid peroxidation in exercising muscle from ALS patients. Amyotroph Lateral Scler Other Motor Neuron Disord 3 2 (2002) 57-62
202. Sjodin B., Hellsten Westing Y., and Apple F.S. Biochemical mechanisms for oxygen free radical formation during exercise. Sports Med 10 4 (1990) 236-254
203. Powers S.K., and Lennon S.L. Analysis of cellular responses to free radicals: focus on exercise and skeletal muscle. Proc Nutr Soc 58 4 (1999) 1025-1033
204. Miyazaki H., Oh-ishi S., Ookawara T., Kizaki T., Toshinai K., Ha S., et al. Strenuous endurance training in humans reduces oxidative stress following exhausting exercise. Eur J Appl Physiol 84 1-2 (2001) 1-6
205. Holloszy J.O., Oscai L.B., Don I.J., and Mole P.A. Mitochondrial citric acid cycle and related enzymes: adaptive response to exercise. Biochem Biophys Res Commun 40 6 (1970) 1368-1373
206. Mahoney D.J., Rodriguez C., Devries M., Yasuda N., and Tarnopolsky M.A. Effects of high-intensity endurance exercise training in the G93A mouse model of amyotrophic lateral sclerosis. Muscle Nerve 29 5 (2004) 656-662
207. Mahoney D.J., Kaczor J.J., Bourgeois J., Yasuda N., and Tarnopolsky M.A. Oxidative stress and antioxidant enzyme upregulation in SOD1-G93A mouse skeletal muscle. Muscle Nerve 33 6 (2006) 809-816
208. Klintsova A.Y., Cowell R.M., Swain R.A., Napper R.M., Goodlett C.R., and Greenough W.T. Therapeutic effects of complex motor training on motor performance deficits induced by neonatal binge-like alcohol exposure in rats. I. Behavioral results. Brain Res. 800 1 (1998) 48-61
209. van Praag H., Christie B.R., Sejnowski T.J., and Gage F.H. Running enhances neurogenesis, learning, and long-term potentiation in mice. Proc Natl Acad Sci U S A 96 23 (1999) 13427-13431
210. Carro E., Trejo J.L., Busiguina S., and Torres-Aleman I. Circulating insulin-like growth factor I mediates the protective effects of physical exercise against brain insults of different etiology and anatomy. J Neurosci 21 15 (2001) 5678-5684
211. Kaspar B.K., Llado J., Sherkat N., Rothstein J.D., and Gage F.H. Retrograde viral delivery of IGF-1 prolongs survival in a mouse ALS model. Science 301 5634 (2003) 839-842
212. Kaspar B.K., Frost L.M., Christian L., Umapathi P., and Gage F.H. Synergy of insulin-like growth factor-1 and exercise in amyotrophic lateral sclerosis. Ann Neurol 57 5 (2005) 649-655
213. Kirkinezos I.G., Hernandez D., Bradley W.G., and Moraes C.T. Regular exercise is beneficial to a mouse model of amyotrophic lateral sclerosis. Ann Neurol 53 6 (2003) 804-807
214. Veldink J.H., Bar P.R., Joosten E.A., Otten M., Wokke J.H., and van den Berg L.H. Sexual differences in onset of disease and response to exercise in a transgenic model of ALS. Neuromuscul Disord 13 9 (2003) 737-743
215. Tiidus P.M., and Bombardier E. Oestrogen attenuates post-exercise myeloperoxidase activity in skeletal muscle of male rats. Acta Physiol Scand 166 2 (1999) 85-90
216. Pinto A.C., Alves M., Nogueira A., Evangelista T., Carvalho J., Coelho A., et al. Can amyotrophic lateral sclerosis patients with respiratory insufficiency exercise?. J Neurol Sci 169 1-2 (1999) 69-75
217. Bello-Haas V.D., Florence J.M., Kloos A.D., Scheirbecker J., Lopate G., Hayes S.M., et al. A randomized controlled trial of resistance exercise in individuals with ALS. Neurology 68 23 (2007) 2003-2007
218. DiBernardo A.B., and Cudkowicz M.E. Translating preclinical insights into effective human trials in ALS. Biochim Biophys Acta 1762 11-12 (2006) 1139-1149
219. Desport J.C., Preux P.M., Magy L., Boirie Y., Vallat J.M., Beaufrere B., et al. Factors correlated with hypermetabolism in patients with amyotrophic lateral sclerosis. Am J Clin Nutr 74 3 (2001) 328-334
220. Desport J.C., Torny F., Lacoste M., Preux P.M., and Couratier P. Hypermetabolism in ALS: correlations with clinical and paraclinical parameters. Neurodegener Dis 2 3-4 (2005) 202-207
221. Desport J.C., Preux P.M., Truong C.T., Courat L., Vallat J.M., and Couratier P. Nutritional assessment and survival in ALS patients. Amyotroph Lateral Scler Other Motor Neuron Disord 1 2 (2000) 91-96
222. Kato S. Amyotrophic lateral sclerosis models and human neuropathology: similarities and differences. Acta Neuropathol 115 1 (2008) 97-114
223. Benatar M. Lost in translation: treatment trials in the SOD1 mouse and in human ALS. Neurobiol Dis 26 1 (2007) 1-13
224. Benatar M., Polak M., Kaplan S., and Glass J. Preventing familial amyotrophic lateral sclerosis: is a clinical trial feasible?. J Neurol Sci 251 1-2 (2006) 3-9
225. Miller R.G., Mitchell J.D., Lyon M., and Moore D.H. Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Cochrane Database Syst Rev 1 (2007) CD001447