Amyotrophic Lateral Sclerosis (Lou Gehrig's Disease) References

Disease Prevention and Treatment, 5th edition

The references on this page correspond with the print version of Disease Prevention and Treatment, 5th edition. Since we continuously update the protocols online in response to new scientific developments, readers are encouraged to review the latest versions of the protocols.

  1. ALS Association (ALSA). Available at: Accessed 3/14/2012
  2. Rowland L. Amyotrophic lateral sclerosis: theories and therapies. J Neorol Sci. 1994;31(169):126–127.
  3. Cleveland DW. From Charcot to SOD1: mechanisms of selective motor neuron death in ALS. Neuron. 1999;24(3):515–520.
  4. Rothstein JD. Current hypotheses for the underlying biology of amyotrophic lateral sclerosis. Ann Neurol. 2009 Jan;65Suppl1:S3-9.
  5. Woodall CJ and Graham DI. Evidence for neuronal localisation of enteroviral sequences in motor neurone disease/amyotrophic lateral sclerosis by in situ hybridization The European Journal of Histochemistry, 2004; 48(2).
  6. Mitchell J. Amyotrophic lateral sclerosis: toxins and environment. Amyotroph Lateral Scler Other Motor Neuron Disord. 2000;1(4):235–250.
  7. Miller RG, et al. Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Cochrane Database Syst Rev. 2007 Jan 24;(1):CD001447.
  8. Sung JJ, Kim HJ, et al. Homocysteine induces oxidative cytotoxicity in Cu, Zn-superoxide dismutase mutant motor neuronal cell. Neuroreport. 2002;13(4):377–381.
  9. Andersen PM. Amyotrophic lateral sclerosis associated with mutations in the CuZn superoxide dismutase gene. CurrNeurolNeurosci Rep 2006; 6:37.
  10. Chiò A, Traynor BJ, Lombardo F, et al. Prevalence of SOD1 mutations in the Italian ALS population. Neurology 2008; 70:533.
  11. Karch CM, Prudencio M, Winkler DD, et al. Role of mutant SOD1 disulfide oxidation and aggregation in the pathogenesis of familial ALS. ProcNatlAcadSci USA 2009; 106:7774.
  12. Lindberg MJ, Tibell L, Oliveberg M. Common denominator of Cu/Zn superoxide dismutase mutants associated with amyotrophic lateral sclerosis: decreased stability of the apo state. ProcNatlAcadSci USA 2002; 99:16607.
  13. Miana-Mena FJ, Gonzalez-Mingot C, et al. Monitoring systemic oxidative stress in an animal model of amyotrophic lateral sclerosis J Neurol (2011) 258:762–769.
  14. Hensley K, Mhatre M, et al. On the Relation of Oxidative Stress to Neuroinflammation: Lessons Learned from the G93A-SOD1 Mouse Model of Amyotrophic Lateral Sclerosis. Antioxidants & Redox Signaling, 2006; 8(11-12).
  15. IlievaEV, Ayala V, et al. Oxidative and endoplasmic reticulum stress interplay in sporadic amyotrophic lateral sclerosis Brain (2007), 130.
  16. Kanekura K, Suzuki H, et al. ER Stress and Unfolded Protein Response in Amyotrophic Lateral Sclerosis. MolNeurobiol (2009) 39:81–89.
  17. Dawson MI. The importance of vitamin A in nutrition. Curr Pharm Des. 2000 Feb;6(3):311-25.
  18. Mandl J, et al.Vitamin C: update on physiology and pharmacology. Br J Pharmacol. 2009 Aug;157(7):1097-110. Epub 2009 Jun 5.
  19. Colombo ML. An update on vitamin E, tocopherol and tocotrienol-perspectives. Molecules. 2010 Mar 24;15(4):2103-13.
  20. Sanmartin C, et al. Selenium and clinical trials: new therapeutic evidence for multiple diseases. Curr Med Chem. 2011;18(30):4635-50.
  21. Rothstein JD, Kuncl RW. Neuroprotective strategies in the model of chronic glutamate-mediated motor neuron toxicity. J Neurochem. 1995b;65(2):643-51.
  22. Cameron A, Rosenfeld J. Nutritional issues and supplements in amyotrophic lateral sclerosis and other neurodegenerative disorders. CurrOpinClinNutrMetab Care. 2002;5(6):631–643.
  23. Rothstein JD, Tsai G, KunclRW, et al. Abnormal excitatory amino acid metabolism in amyotrophic lateral sclerosis. Ann Neurol 1990; 28:18.
  24. Shaw PJ, Forrest V, Ince PG, et al. CSF and plasma amino acid levels in motor neuron disease: elevation of CSF glutamate in a subset of patients. Neurodegeneration 1995; 4:209.
  25. Lin CL, Bristol LA, Jin L, et al. Aberrant RNA processing in a neurodegenerative disease: the cause for absent EAAT2, a glutamate transporter, in amyotrophic lateral sclerosis. Neuron 1998; 20:589.
  26. Rothstein JD, Van Kammen M, Levey AI, et al. Selective loss of glial glutamate transporter GLT-1 in amyotrophic lateral sclerosis. Ann Neurol 1995; 38:73.
  27. Dunlop J, Beal McIlvain H, She Y, Howland DS. Impaired spinal cord glutamate transport capacity and reduced sensitivity to riluzole in a transgenic superoxide dismutase mutant rat model of amyotrophic lateral sclerosis. J Neurosci 2003; 23:1688.
  28. Brand MD and Nicholls DG. Assessing mitochondrial dysfunction in cells. Biochem J. 2011 Apr 15;435(2):297-312.
  29. Shi P, Gal J, et al. Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis. Biochimica et BiophysicaActa 1802 (2010) 45–51.
  30. Kong J, Xu Z. Massive mitochondrial degeneration in motor neurons triggers the onset of amyotrophic lateral sclerosis in mice expressing a mutant SOD1. J Neurosci 1998; 18:3241.
  31. Liu J, Lillo C, Jonsson PA, et al. Toxicity of familial ALS-linked SOD1 mutants from selective recruitment to spinal mitochondria. Neuron 2004; 43:5.
  32. Cassarino DS, Bennett JP Jr. An evaluation of the role of mitochondria in neurodegenerative diseases: mitochondrial mutations and oxidative pathology, protective nuclear responses, and cell death in neurodegeneration. Brain Res Brain Res Rev 1999;29:1.
  33. Beal MF. Mitochondria take center stage in aging and neurodegeneration. Ann Neurol. 2005;58:495.
  34. Martin LJ. Mitochondrial pathobiology in ALS. J Bioenerg Biomembr. 2011;43(6):569-79.
  35. Cozzolino M and Carri MT. Mitochondrial Dysfunction in ALS. Progress in Neurobiology, 2011.
  36. Kawamata K and Manfredi G. Mitochondrial Dysfunction and Intracellular Calcium Dysregulation in ALS. Mechanisms of Ageing and Development, 2011; 131(7-8).
  37. Faes L and Callewaert G. Mitochondrial Dysfunction in Familial Amyotrophic Lateral Sclerosis. Journal of Bioenergetics and Biomembranes, 2011; 43(6).
  38. Crugnola V, Lamperti C, et al. Mitochondrial Respiratory Chain Dysfunction in Muscle From Patients With Amyotrophic Lateral Sclerosis. Arch Neurol. 2010;67(7):849-854.
  39. De Vos KJ, Chapman AL, et al. Familial amyotrophic lateral sclerosis-linked SOD1 mutants perturb fast axonal transport to reduce axonal mitochondria content. Human Molecular Genetics, 2007; 16(22).
  40. Fosslien E. Mitochondrial medicine—molecular pathology of defective oxidative phosphorylation. Ann Clin Lab Sci. 2001;31(1):25–67.
  41. VadakkadathMeethal S and Atwood CS. e dyscrasia: a novel explanation for amyotrophic lateral sclerosis. Neurobiol Aging. 2012 Mar;33(3):569-81.
  42. Matsumoto Y, et al. Nizofenone, a neuroprotective drug, suppresses glutamate release and lactate accumulation. Eur J Pharmacol. 1994 Sep 1;262(1-2):157-61.
  43. Fang F, Kwee LC, et al. Association Between Blood Lead and the Risk of Amyotrophic Lateral Sclerosis. American Journal of Epidemiology, 2010; 171(10).
  44. Callaghan B, Feldman D, et al. The Association of Exposure to Lead, Mercury, and Selenium and the Development of Amyotrophic Lateral Sclerosis and the Epigenetic Implications. Neurodegenerative Dis 2011;8:1–8.
  45. Mano Y, Takayanagi T, et al. [Amyotrophic lateral sclerosis and mercury—preliminary report]. RinshoShinkeigaku. 1990;30(11):1275–1277.
  46. Rooney J. Further Thoughts on Mercury, Epigenetics, Genetics and Amyotrophic Lateral Sclerosis. Neurodegenerative Dis 2011;8:523–524.
  47. Gresham LS, Molgaard CA , et al. Amyotrophic lateral sclerosis and occupational heavy metal exposure: a case-control study. Neuroepidemiology. 1986;5(1):29–38.
  48. Banack SA, Caller TA, et al. The Cyanobacteria Derived Toxin Beta-N-Methylamino-L-Alanine and Amyotrophic Lateral Sclerosis. Toxins (Basel), 2010;2(12).
  49. Johnson FO and Atchison WD. The role of environmental mercury, lead and pesticide exposure in development of amyotrophic lateral sclerosis. NeuroToxicology 30 (2009) 761–765.
  50. Chio A, Calva A, et al. ALS in Italian professional soccer players: The risk is still present and could be soccer-specific. Amyotrophic Lateral Sclerosis, 2009.
  51. Caban-Holt A, Mattingly M, et al. Neurodegenerative memory disorders: a potential role of environmental toxins. NeurolClin. 2005;23(2):485–521.
  52. Rowland LP, Shneider NA. Amyotrophic lateral sclerosis. N Engl J Med. 2001;344(22):1688–1700.
  53. Carlesi C, et al. Strategies for clinical approach to neurodegeneration in Amyotrophic lateral sclerosis. Arch Ital Biol. 2011 Mar;149(1):151-67.
  54. Mustfa N, Walsh E, Bryant V, et al. The effect of noninvasive ventilation on ALS patients and their caregivers. Neurology 2006; 66:1211.
  55. Lo Coco D, Marchese S, Pesco MC, et al. Noninvasive positive-pressure ventilation in ALS: predictors of tolerance and survival. Neurology 2006; 67:761.
  56. Andersen PM, Borasio GD, Dengler R, et al. EFNS task force on management of amyotrophic lateral sclerosis: guidelines for diagnosing and clinical care of patients and relatives. Eur J Neurol 2005; 12:921.
  57. Giess R, Naumann M, Werner E, et al. Injections of botulinum toxin A into the salivary glands improve sialorrhoea in amyotrophic lateral sclerosis. J NeurolNeurosurg Psychiatry 2000; 69:121.
  58. Lipp A, Trottenberg T, Schink T, et al. A randomized trial of botulinum toxin A for treatment of drooling. Neurology 2003; 61:1279.
  59. Stone CA, O'Leary N. Systematic review of the effectiveness of botulinum toxin or radiotherapy for sialorrhea in patients with amyotrophic lateral sclerosis. J Pain Symptom Manage 2009; 37:246.
  60. Borasio GD, Voltz R, Miller RG. Palliative care in amyotrophic lateral sclerosis. NeurolClin 2001;19:829.
  61. Martinez HR, et al. Stem-cell transplantation into the frontal motor cortex in amyotrophic lateral sclerosis patients. Cytotherapy. 2009;11(1):26-34.
  62. Martinez HR, et al. Stem cell transplantation in amyotrophic lateral sclerosis patients. Methodological approach, safety, and feasibility. Cell Transplant. 2012 Feb 13. [Epub ahead of print]
  63. Suzuki M and SvendsenCN. Combining growth factor and stem cell therapy for amyotrophic lateral sclerosis. Trends in Neurosciences, 2008; 31(4).
  64. LunnJS, Hefferan MP, et al. Stem cells: comprehensive treatments for amyotrophic lateral sclerosis in conjunction with growth factor delivery. Growth Factors, June 2009; 27(3): 133–140.
  65. Mackenzie IR, Bigio EH, et al. Pathological TDP-43 distinguishes sporadic amyotrophic lateral sclerosis from amyotrophic lateral sclerosis with SOD1 mutations. Annals of Neurology, 2007; 61(5).
  66. Kwiatkowski TJ, et al. Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science. 2009 Feb 27;323(5918):1205-8.
  67. Vance C, et al. Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science. 2009 Feb 27;323(5918):1208-11.
  68. Lagier-Tourenne C and Cleveland DW. Rethinking ALS: The FUS about TDP-43. Cell 136, March 20, 2009.
  69. Hester ME, FouseKD, et al. AAV as a Gene Transfer Vector for the Treatment of Neurological Disorders: Novel Treatment Thoughts for ALS. Current Gene Therapy, Volume 9, Number 5, October 2009, pp. 428-433(6).
  70. Yamashita M, Nonaka T, et al. Methylene blue and dimebon inhibit aggregation of TDP-43 in cellular models FEBS Letters, 2009; 583(14).
  71. Sakowski SA, Schuyler AD, et al. Insulin-like growth factor-I for the treatment of amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis, 2009; 10(2).
  72. Nagano I, Shiote M, et al. Beneficial effects of intrathecalIGF-1 administration in patients with amyotrophic lateral sclerosis. Neurological Research, 2005; 27(7).
  73. Sorenson EJ, WindbankAJ, et al. Subcutaneous IGF-1 is not beneficial in 2-year ALS trial. Neurology, 2008; 71(22).
  74. Franz CK, Federici T, Yang J, et al. Intraspinal cord delivery of IGF-1 mediated by adeno-associated virus 2 is neuroprotective in a rat model of familial ALS. Neurobiol Dis. 2009;33(3):473-81.
  75. Lepore AC, Haenggeli C, et al. Intraparenchymal spinal cord delivery of adeno-associated virus IGF-1 is protective in the SOD1G93A model of ALS. Brain Research, 2007; 1185.
  76. Morselli LL, et al. Growth hormone secretion is impaired in amyotrophic lateral sclerosis. ClinEndocrinol (Oxf). 2006 Sep;65(3):385-8.
  77. Sacca F, et al. A randomized controlled clinical trial of growth hormone in amyotrophic lateral sclerosis: clinical, neuroimaging, and hormonal results. J Neurol. 2012 Jan;259(1):132-8. Epub 2011 Jun 25.
  78. Phukan J. Arimoclomol, a coinducer of heat shock proteins for the potential treatment of amyotrophic lateral sclerosis. IDrugs. 2010;13(7):482-96.
  79. Rothstein JD, et al. Beta-lactam antibiotics offer neuroprotection by increasing glutamate transporter expression. Nature. 2005 Jan 6;433(7021):73-7.
  80. Cheah BC and Kiernan MC. Dexpramipexole, the R(+) enantiomer of pramipexole, for the potential treatment of amyotrophic lateral sclerosis. IDrugs. 2010 Dec;13(12):911-20.
  81. Bozik ME, Mather JL, Kramer WG, et al. Safety, tolerability, and pharmacokinetics of KNS-760704 (dexpramipexole) in healthy adult subjects. J ClinPharmacol 2011;51:1177.
  82. Safety and Efficacy of TRO19622 as add-on Therapy to Riluzole Versus Placebo in Treatment of Patients Suffering From Amyotrophic Lateral Sclerosis (ALS) (MITOTARGET). Updated 05/2010: Accessed 03/06/2012.
  83. Therapeutic Pipeline Accessed 3/16/2012
  84. Izumi Y and Kaji R. [Clinical trials of ultra-high-dose methylcobalamin in ALS]. Brain Nerve. 2007 Oct;59(10):1141-7.
  85. Ganji V and Kafal MR. Population prevalence, attributable risk, and attributable risk percentage for high methylmalonic acid concentrations in the post-folic acid fortification period in the US. Nutrition & Metabolism 2012, 9:2.
  86. Leishear K, Lucci F, et al. Vitamin B12 and Homocysteine Levels and 6-Year Change in Peripheral Nerve Function and Neurological Signs. Journal of Gerentology, 2011.
  87. PottJW, Wassink-RuiterJS, et al. Methylmalonic acid and homocysteine assessment in the detection of vitamin B12 deficiency in patients with bilateral visual loss. ActaOpthamologica, 2012.
  88. Moore E, Mander A, et al. Cognitive impairment and vitamin B12: a review. International Psycogeriatrics, 2012.
  89. Ermilova IP, Ermilov VB, et al. Protection by dietary zinc in ALS mutant G93A SOD transgenic mice. NeurosciLett. 2005;379(1):42–46.
  90. Trumbull KA and Beckman JS. A Role for Copper in the Toxicity of Zinc-Deficient Superoxide Dismutase to Motor Neurons in Amyotrophic Lateral Sclerosis. Antioxid Redox Signal. 2009 Jul;11(7):1627-39.
  91. Grabrucker AM, Rowan M, et al. Brain-Delivery of Zinc-Ions as Potential Treatment for Neurological Diseases: Mini Review. Drug DelivLett. 2011 September;1(1): 13–23.
  92. Jiang F, DeSilva S, et al. Beneficial effect of ginseng root in SOD-1 (G93A) transgenic mice. J NeurolSci, 2000;180(1–2):52–54.
  93. Kim YH, Park KH, et al. Transcriptional Activation of the Cu,Zn-Superoxide Dismutase gene through the AP2 site by ginsenosideRb2 extracted from a medicinal plant, Panax ginseng. J Biol Chem. 1996 Oct 4;271(40):24539-43.
  94. Radad K, Moldzio R, et al. Ginsenosides and their CNS Targets. CNS Neuroscience and Therapeutics, 2011; 17.
  95. Ernst E. The risk-benefit profile of commonly used herbal therapies: Ginkgo, St. John's Wort, Ginseng, Echinacea, Saw Palmetto, and Kava. Ann Intern Med. 2002;136(1):42–53.
  96. Kobayashi MS, Han D, Packer L. Antioxidants and herbal extracts protect HT-4 neuronal cells against glutamate-induced cytotoxicity. Free Radic Res. 2000;32(2):115–124.
  97. Ferrante RJ, Klein AM, et al. Therapeutic efficacy of EGb761 ( Gingko biloba extract) in a transgenic mouse model of amyotrophic lateral sclerosis. J MolNeurosci. 2001;17(1):89–96.
  98. Shi C, Zhao L, et al. Dosage Effects of EGb761 on Hydrogen Peroxide-Induced Cell Death in SH-SY5Y Cells. ChemBiol Interact, 2009; 180(3):389-97.
  99. Mancuso M, Orsucci D, et al. Coenzyme Q10 in Neuromuscular and Neurodegenerative Disorders. Current Drug Targets, 2010, 11, 111-121.
  100. Sohmiya M, Tanaka M, et al. An increase of oxidized coenzyme Q-10 occurs in the plasma of sporadic ALS patients. J Neurol Sci. 2005;228(1):49–53.
  101. Matthews RT, Yang L, et al. Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects. ProcNatlAcadSci USA. 1998;95(15):8892–8897.
  102. Kauffman P, Thompson JL, et al. Phase II Trial of CoQ10 for ALS Finds Insufficient Evidence to Justify Phase III. Ann Neurol. 2009;66:235–244.
  103. Ferrante KL, Shefner J, et al. Tolerance of high-dose (3,000 mg/day) coenzyme Q10 in ALS. Neurology December 13, 2005 vol. 65 no. 11: 1834-1836.
  104. Carta A, Calvani M, et al. Acetyl-L-carnitine and Alzheimer's disease: pharmacological considerations beyond the cholinergic sphere. Ann N Y Acad Sci. 1993;695:324–326.
  105. Virmani A, Gaetani F, et al. The Protective Role of L-Carnitine against Neurotoxicity Evoked by Drug of Abuse, Methamphetamine, Could Be Related to Mitochondrial Dysfunction. Ann. N.Y. Acad. Sci. 965: 225–232 (2002).
  106. Jin HW, Flatters SJ, et al. Prevention of paclitaxel-evoked painful peripheral neuropathy by acetyl-L-carnitine: Effects on axonal mitochondria, sensory nerve fiber terminal arbors, and cutaneous Langerhans cells. Experimental Neurology 210 (2008) 229–237.
  107. Wilson AD, Hart A, et al. Acetyl-l-carnitine increases nerve regeneration and target organ reinnervation – a morphological study. The Journal of Plastic, Reconstructive and Aesthetic Surgery, 2010; 63(7).
  108. KokkalisZT, SoucacosPN, et al. Effect of Acetyl-L-Carnitine on Axonal Sprouting Following Donor Nerve Injury Distal to an End-to-Side Neurorrhaphy Model. Journal of reconstructive Microsurgery, 2009; 25(8).
  109. BabuGN, Kumar A, et al. Chronic Pretreatment with Acetyl-l-Carnitine and ±DL-α-Lipoic Acid Protects Against Acute Glutamate-Induced Neurotoxicity in Rat Brain by Altering Mitochondrial Function. Neurotoxicity Research, 2009;19(2).
  110. Bigini P, Larini S, et al. Acetyl-l-carnitine shows neuroprotective and neurotrophic activity in primary culture of rat embryo motoneurons. Neuroscience Letters 329 (2002) 334–338.
  111. Kira Y, Nishikawa M, et al. L-Carnitine suppresses the onset of neuromuscular degeneration and increases the life span of mice with familial amyotrophic lateral sclerosis. Brain Research, 2006; 1070.
  112. Hagen TM, Liu J, et al. Feeding acetyl-L-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress. ProcNatlAcadSci USA. 2002;99(4):1870–1875.
  113. SuhJH, ShenviSV, et al. Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid. PNAS, 2004a; 101(10).
  114. Yamada T, Hashida K, et al. α-Lipoic acid (LA) enantiomers protect SH-SY5Y cells against glutathione depletion. Neurochemistry International, 2011; 59(7).
  115. SuhJH, Zhu BZ, DeSzoeke E, et al. Dihydrolipoic acid lowers the redox activity of transition metal ions but does not remove them from the active site of enzymes. Redox Rep.2004b;9:5761.
  116. SuhJH, Moreau R, Heath SH, Hagen TM. Dietary supplementation with (R)-alpha-lipoic acid reverses the age-related accumulation of iron and depletion of antioxidants in the rat cerebral cortex. Redox Rep.2005;10:5260.
  117. Liu J. The Effects and Mechanisms of Mitochondrial Nutrient α-Lipoic Acid on Improving Age-Associated Mitochondrial and Cognitive Dysfunction: An Overview. Biomedical and Life Sciences, 2008; 33(1).
  118. Muller U, Krieglstein J. Prolonged pretreatment with alpha-lipoic acid protects cultured neurons against hypoxic, glutamate-, or iron-induced injury. J Cereb Blood Flow Metab. 1995;15(4):624–630.
  119. Andreassen OA, Dedeoglu A, et al. Effects of an inhibitor of poly(ADP-ribose) polymerase, desmethylselegiline, trientine, and lipoic acid in transgenic ALS mice. Exp Neurol. 2001b;168(2):419–424.
  120. Carvalho-Silva LB, Mourao LF, et al. Effect of nutritional supplementation with milk whey proteins in amyotrophic lateral sclerosis patients. Arquivos de Neuro-Psiquiatria, 2010; 68(2).
  121. Ross E, Wilkins H, et al. A non-denatured whey protein supplement (Immunocal®) protects neurons from mitochondrial oxidative stress and delays disease onset in the mutant SOD1 mouse model of ALS. 2011.
  122. Palma A, de Carvalho M, et al. Biochemical characterization of plasma in amyotrophic lateral sclerosis: amino acid and protein composition. Amyotoph Lateral Scler Other Motor Neuron Disord. 2005;6(2):104–110.
  123. Persky AM, Brazeau GA. Clinical pharmacology of the dietary supplement creatine monohydrate. Pharmacol Rev. 2001;53(2):161–176.
  124. Andreassen OA, Jenkins BG, et al. Increases in cortical glutamate concentrations in transgenic amyotrophic lateral sclerosis mice are attenuated by creatine supplementation. J Neurochem. 2001a; 77(2):383–390.
  125. Vielhaber S, Kaufmann J, et al. Effect of creatine supplementation on metabolite levels in ALS motor cortices. Exp Neurol. 2001;172(2):377–382.
  126. Mazzini L, Balzarini C, et al. Effects of creatine supplementation on exercise performance and muscular strength in amyotrophic lateral sclerosis: preliminary results. J Neurol Sci. 2001;191(1–2):139–144.
  127. Klopstock T, Elstner M, et al. Creatine in mouse models of neurodegeneration and aging. Amino Acids (2011) 40:1297–1303.
  128. Beal MF. Neuroprotective Effects of Creatine. Amino Acids (2011) 40:1305–1313.
  129. PastulaDM, Moore DH, et al. Creatine for amyotrophic lateral sclerosis/motor neuron disease. The Cochrane Collaboration, 2010.
  130. Atassi N, RataiEM, et al. A phase I, pharmacokinetic, dosage escalation study of creatine monohydrate in subjects with amyotrophic lateral sclerosis. Amyotroph Lateral Scler. 2010 December;11(6): 508–513.
  131. Exner R, Wessner B, et al. Therapeutic potential of glutathione. Wien KlinWochenschr. 2000;112(14):610–616.
  132. Carmeli C, Knyazeva MG, et al. Glutathione Precursor N-Acetyl-Cysteine Modulates EEG Synchronization in Schizophrenia Patients: A Double-Blind, Randomized, Placebo-Controlled Trial. PLos One, 2012;7(2).
  133. Baillet A, Chantepedrix V, et al. The Role of Oxidative Stress in Amyotrophic Lateral Sclerosis and Parkinson’s Disease. Neurochem Res (2010) 35:1530–1537.
  134. Vargas MR, Johnson DA, et al. Nrf2 Activation in Astrocytes Protects against Neurodegeneration in Mouse Models of Familial Amyotrophic Lateral Sclerosis. The Journal of Neuroscience, December 10, 2008; 28(50):13574 –13581.
  135. D’Alessandro G, Calcagno E, et al. Glutamate and glutathione interplay in a motor neuronal model of amyotrophic lateral sclerosis reveals altered energy metabolism. Neurobiology of Disease 2011; 43.
  136. Andreassen OA, Dedeoglu A, et al. N-acetyl-L-cysteine improves survival and preserves motor performance in an animal model of familial amyotrophic lateral sclerosis. Neuroreport. 2000;11(11):2491–2493.
  137. Henderson JT, Javaheri M, et al. Reduction of lower motor neuron degeneration in wobbler mice by N-acetyl-L-cysteine. J Neurosci. 1996;16(23):7574–7582.
  138. Kuhnlein P, Gdynia HJ, et al. Diagnosis and treatment of bulbar symptoms in amyotrophic lateral sclerosis. Nature Clinical Practice, 2008; 4(7).
  139. Hu M, SkibstedLH. Kinetics of reduction of ferrylmyoglobin by (-)-epigallocatechingallate and green tea extract. J Agric Food Chem. 2002;50(10):2998–3003.
  140. Hong JT, Ryu SR, et al. Neuroprotective effect of green tea extract in experimental ischemia-reperfusion brain injury. Brain Res Bull. 2000;53(6):743–749.
  141. Mandel SA, Amit T, et al. Targeting Multiple Neurodegenerative Diseases Etiologies with Multimodal-Acting Green Tea Catechins. The Journal of Nutrition, 2008.
  142. Yu J, Jia Y, et al. Epigallocatechin-3-gallate Protects Motor Neurons and Regulates Glutamate Levels. FEBS Letters 584 (2010) 2921–2925.
  143. Schroeder EK, Keley NA, et al. Green Tea Epigallocatechin 3-Gallate Accumulates in Mitochondria and Displays a Selective Antiapoptotic Effect Against Inducers of Mitochondrial Oxidative Stress in Neurons. Antioxidants & Redox Signaling. March 2009, 11(3): 469-480.
  144. Benkler C, Offen D, et al. Recent advances in amyotrophic lateral sclerosis research: perspectives for personalized clinical application. EPMA Journal (2010) 1:343–361.
  145. Mandel SA, Amit T, et al. Understanding the Broad-Spectrum Neuroprotective Action Profile of Green Tea Polyphenols in Aging and Neurodegenerative Diseases. Journal of Alzheimer’s Disease, 2011; 25(2).
  146. Morozova N, Weisskopf MG, et al. Diet and Amytorophic Lateral Sclerosis. Epidemiology, 2008; 19(2).
  147. Packer L, Rimbach G, et al. Antioxidant activity and biologic properties of a procyanidin-rich extract from pine (Pinusmaritima) bark, pycnogenol. Free RadicBiol Med. 1999;27(5–6):704–724.
  148. Kolacek M, Muchova J, et al. Effect of Natural Polyphenols, Pycnogenol® on Superoxide Dismutase and Nitric Oxide Synthase in Diabetic Rats. Prague Medical Report, 2010; 111 (4).
  149. Wu SN. Large-conductance Ca2+- activated K+ channels: physiological role and pharmacology. Curr Med Chem. 2003;10(8):649–661.
  150. Sun AY, Wang Q, et al. Resveratrol as a Therapeutic Agent for Neurodegenerative Diseases. MolNeurobiol (2010) 41:375–383.
  151. Kim D, Nguyen MD, et al. SIRT1deacetylase protects against neurodegeneration in models for Alzheimer’s disease and amyotrophic lateral sclerosis. The EMBO Journal (2007) 26, 3169–3179.
  152. Wang J, Zhang Y, et al. Protective effects of resveratrol through the up-regulation of SIRT1 expression in the mutant hSOD1-G93A-bearing motor neuron-like cell culture model of amyotrophic lateral sclerosis. Neuroscience Letters 503 (2011) 250– 255.
  153. Yoon DH, Kwon OY, et al. Protective potential of resveratrol against oxidative stress and apoptosis in Batten disease lymphoblast cells. Biochemical and Biophysical Research Communications 414 (2011) 49–52.
  154. Yanez M, Galan L, et al. CSF from amyotrophic lateral sclerosis patients produces glutamate independent death of rat motor brain cortical neurons: Protection by resveratrol but not riluzole. Brain Research, 2011; 1423.