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Food, Nutrigenomics, and Neurodegeneration—Neuroprotection by What You Eat!

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Abstract

Diet in human health is no longer simple nutrition, but in light of recent research, especially nutrigenomics, it is linked via evolution and genetics to cell health status capable of modulating apoptosis, detoxification, and appropriate gene response. Nutritional deficiency and disease especially lack of vitamins and minerals is well known, but more recently, epidemiological studies suggest a role of fruits and vegetables, as well as essential fatty acids and even red wine (French paradox), in protection against disease. In the early 1990s, various research groups started considering the use of antioxidants (e.g., melatonin, resveratrol, green tea, lipoic acid) and metabolic compounds (e.g., nicotinamide, acetyl-l-carnitine, creatine, coenzyme Q10) as possible candidates in neuroprotection. They were of course considered on par with snake oil salesman (women) at the time. The positive actions of nutritional supplements, minerals, and plant extracts in disease prevention are now mainstream and commercial health claims being made are subject to regulation in most countries. Apart from efficacy and finding, the right dosages, the safety, and especially the level of purification and lack of contamination are all issues that are important as their use becomes widespread. From the mechanistic point of view, most of the time these substances replenish the body’s deficiency and restore normal function. However, they also exert actions that are not sensu stricto nutritive and could be considered pharmacological especially that, at times, higher intake than recommended (RDA) is needed to see these effects. Free radicals and neuroinflammation processes underlie many neurodegenerative conditions, even Parkinson’s disease and Alzheimer’s disease. Curcumin, carotenoids, acetyl-l-carnitine, coenzyme Q10, vitamin D, and polyphenols and other nutraceuticals have the potential to target multiple pathways in these conditions. In summary, augmenting neuroprotective pathways using diet and finding new natural substances that can be more efficacious, i.e., induction of health-promoting genes and reduction of the expression of disease-promoting genes, could be incorporated into neuroprotective strategies of the future.

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References

  1. Virmani A, Binienda Z, Ali S, Gaetani F (2006) Links between nutrition, drug abuse, and the metabolic syndrome. Ann N Y Acad Sci 1074:303–14

    Article  CAS  PubMed  Google Scholar 

  2. Joseph J, Cole G, Head E, Ingram D (2009) Nutrition, brain aging, and neurodegeneration. J Neurosci 29:12795–801

    Article  CAS  PubMed  Google Scholar 

  3. Lillycrop KA, Burdge GC (2012) Epigenetic mechanisms linking early nutrition to long term health. Best Pract Res Clin Endocrinol Metab 26:667–76

    Article  PubMed  Google Scholar 

  4. Williams M (2011) Qualitative pharmacology in a quantitative world: diminishing value in the drug discovery process. Curr Opin Pharmacol 11:496–500

    Article  CAS  PubMed  Google Scholar 

  5. Deitrich R, Zimatkin S, Pronko S (2006) Oxidation of ethanol in the brain and its consequences. Alcohol Res Health 29:266–73

    PubMed  Google Scholar 

  6. Jukes TH (1989) The prevention and conquest of scurvy, beri-beri, and pellagra. Prev Med 18:877–83

    Article  CAS  PubMed  Google Scholar 

  7. Boeing H, Bechthold A, Bub A, Ellinger S, Haller D, Kroke A, Leschik-Bonnet E, Müller MJ, Oberritter H, Schulze M, Stehle P, Watzl B (2012) Critical review: vegetables and fruit in the prevention of chronic diseases. Eur J Nutr 51:637–63

    Article  CAS  PubMed  Google Scholar 

  8. NIH Office of Dietary Supplements (2012) Dietary supplements: what you need to know NIH Office of Dietary Supplements Web site. Accessed at ods.od.nih.gov/HealthInformation/DS_WhatYouNeedToKnow.aspx. Accessed 17 June 2011

  9. Gold LS, Slone TH, Ranking MS (1999) Possible toxic hazards of dietary supplements compared to other natural and synthetic substances. Testimony to the FDA, Docket No. 99N-1174

  10. Kelsey NA, Wilkins HM, Linseman DA (2010) Nutraceutical antioxidants as novel neuroprotective agents. Molecules 15:7792–814

    Article  CAS  PubMed  Google Scholar 

  11. Roberts RA, Laskin DL, Smith CV, Robertson FM, Allen EM, Doorn JA, Slikker W (2009) Nitrative and oxidative stress in toxicology and disease. Toxicol Sci 112:4–16

    Article  CAS  PubMed  Google Scholar 

  12. Schroeder EK, Kelsey NA, Doyle J, Breed E, Bouchard RJ, Loucks FA, Harbison RA, Linseman DA (2009) Green tea epigallocatechin 3-gallate accumulates in mitochondria and displays a selective antiapoptotic effect against inducers of mitochondrial oxidative stress in neurons. Antioxid Redox Signal 11:469–80

    Article  CAS  PubMed  Google Scholar 

  13. Wagner AE, Ernst IM, Birringer M, Sancak O, Barella L, Rimbach G (2012) A combination of lipoic acid plus coenzyme Q10 induces PGC1a, a master switch of energy metabolism, improves stress response, and increases cellular glutathione levels in cultured C2C12 skeletal muscle cells. Oxid Med Cell Longev 2012:835970

    Article  CAS  PubMed  Google Scholar 

  14. Matsubara E, Bryant-Thomas T, Pacheco Quinto J, Henry TL, Poeggeler B, Herbert D, Cruz-Sanchez F, Chyan YJ, Smith MA, Perry G, Shoji M, Abe K, Leone A, Grundke-Ikbal I, Wilson GL, Ghiso J, Williams C, Refolo LM, Pappolla MA, Chain DG, Neria E (2003) Melatonin increases survival and inhibits oxidative and amyloid pathology in a transgenic model of Alzheimer’s disease. J Neurochem 85:1101–8

    Article  CAS  PubMed  Google Scholar 

  15. Fischer A, Schmelzer C, Rimbach G, Niklowitz P, Menke T, Döring F (2011) Association between genetic variants in the coenzyme Q10 metabolism and coenzyme Q10 status in humans. BMC Res Notes 21:245

    Article  Google Scholar 

  16. Lappas M, Mitton A, Lim R, Barker G, Riley C, Permezel M (2011) SIRT1 is a novel regulator of key pathways of human labor. Biol Reprod 84:167–78

    Article  CAS  PubMed  Google Scholar 

  17. Calabrese V, Ravagna A, Colombrita C, Scapagnini G, Guagliano E, Calvani M, Butterfield DA, Giuffrida Stella AM (2005) Acetylcarnitine induces heme oxygenase in rat astrocytes and protects against oxidative stress: involvement of the transcription factor Nrf2. J Neurosci Res 79:509–21

    Article  CAS  PubMed  Google Scholar 

  18. Hardy TM, Tollefsbol TO (2011) Epigenetic diet: impact on the epigenome and cancer. Epigenomics 3:503–18

    Article  CAS  PubMed  Google Scholar 

  19. Alam SE, Singh RB, Gupta S, Dherange P, De Meester F, Wilczynska A, Dharwadkar S, Wilson D, Hungin P (2012) Nutritional aspects of epigenetic inheritance. Can J Physiol Pharmacol 90:989–94

    Article  CAS  PubMed  Google Scholar 

  20. Ling C, Groop L (2009) Epigenetics: a molecular link between environmental factors and type 2 diabetes. Diabetes 58:2718–25

    Article  CAS  PubMed  Google Scholar 

  21. Troen BR (2003) The biology of aging. Mt Sinai J Med 70:3–22

    PubMed  Google Scholar 

  22. Chung S, Yao H, Caito S, Hwang JW, Arunachalam G, Rahman I (2010) Regulation of SIRT1 in cellular functions: role of polyphenols. Arch Biochem Biophys 501:79–90

    Article  CAS  PubMed  Google Scholar 

  23. Duan W, Ross CA (2010) Potential therapeutic targets for neurodegenerative diseases: lessons learned from calorie restriction. Curr Drug Targets 11:1281–92

    Article  CAS  PubMed  Google Scholar 

  24. Virmani A, Ali SF, Binienda ZK (2010) Neuroprotective strategies in drug abuse-evoked encephalopathy. Ann N Y Acad Sci 1199:52–68

    Article  CAS  PubMed  Google Scholar 

  25. Lee HH, Yang LL, Wang CC, Hu SY, Chang SF, Lee YH (2003) Differential effects of natural polyphenols on neuronal survival in primary cultured central neurons against glutamate- and glucose deprivation-induced neuronal death. Brain Res 986:103–13

    Article  CAS  PubMed  Google Scholar 

  26. Braidy N, Grant R, Adams S, Guillemin GJ (2010) Neuroprotective effects of naturally occurring polyphenols on quinolinic acid-induced excitotoxicity in human neurons. FEBS J 277:368–82

    Article  CAS  PubMed  Google Scholar 

  27. Renaud S, de Lorgeril M (1992) Wine, alcohol, platelets, and the French paradox for coronary heart disease. Lancet 339:1523–6

    Article  CAS  PubMed  Google Scholar 

  28. Ankarcrona M, Dypbukt JM, Bonfoco E, Zhivotovsky B, Orrenius S, Lipton SA, Nicotera P (1995) Glutamate-induced neuronal death: a succession of necrosis or apoptosis depending on mitochondrial function. Neuron 15:961–73

    Article  CAS  PubMed  Google Scholar 

  29. Campos-Esparza MR, Sánchez-Gómez MV, Matute C (2009) Molecular mechanisms of neuroprotection by two natural antioxidant polyphenols. Cell Calcium 45:358–68

    Article  CAS  PubMed  Google Scholar 

  30. Singleton RH, Yan HQ, Fellows-Mayle W, Dixon CE (2010) Resveratrol attenuates behavioral impairments and reduces cortical and hippocampal loss in a rat controlled cortical impact model of traumatic brain injury. J Neurotrauma 27:1091–9

    Article  PubMed  Google Scholar 

  31. Schinder AF, Olson EC, Spitzer NC, Montal M (1996) Mitochondrial dysfunction is a primary event in glutamate neurotoxicity. J Neurosci 16:6125–33

    CAS  PubMed  Google Scholar 

  32. Tenneti L, Lipton SA (2000) Involvement of activated caspase-3-like proteases in N-methyl-d-aspartate-induced apoptosis in cerebrocortical neurons. J Neurochem 74:134–42

    Article  CAS  PubMed  Google Scholar 

  33. Tenneti L, D’Emilia DM, Troy CM, Lipton SA (1998) Role of caspases in N-methyl-d-aspartate-induced apoptosis in cerebrocortical neurons. J Neurochem 71:946–59

    Article  CAS  PubMed  Google Scholar 

  34. Hirashima Y, Kurimoto M, Nogami K, Endo S, Saitoh M, Ohtani O, Nagata T, Muraguchi A, Takaku A (1999) Correlation of glutamate-induced apoptosis with caspase activities in cultured rat cerebral cortical neurons. Brain Res 849:109–18

    Article  CAS  PubMed  Google Scholar 

  35. Brecht S, Gelderblom M, Srinivasan A, Mielke K, Dityateva G, Herdegen T (2001) Caspase-3 activation and DNA fragmentation in primary hippocampal neurons following glutamate excitotoxicity. Brain Res Mol Brain Res 94:25–34

    Article  CAS  PubMed  Google Scholar 

  36. Gottlieb M, Leal-Campanario R, Campos-Esparza MR, Sánchez-Gómez MV, Alberdi E, Arranz A, Delgado-García JM, Gruart A, Matute C (2006) Neuroprotection by two polyphenols following excitotoxicity and experimental ischemia. Neurobiol Dis 23:374–86

    Article  CAS  PubMed  Google Scholar 

  37. Mercer LD, Kelly BL, Horne MK, Beart PM (2005) Dietary polyphenols protect dopamine neurons from oxidative insults and apoptosis: investigations in primary rat mesencephalic cultures. Biochem Pharmacol 69:339–45

    Article  CAS  PubMed  Google Scholar 

  38. Vafeiadou K, Vauzour D, Spencer JP (2007) Neuroinflammation and its modulation by flavonoids. Endocr Metab Immune Disord Drug Targets 7:211–24

    Article  CAS  PubMed  Google Scholar 

  39. Mandel SA, Avramovich-Tirosh Y, Reznichenko L, Zheng H, Weinreb O, Amit T, Youdim MB (2005) Multifunctional activities of green tea catechins in neuroprotection. Modulation of cell survival genes, iron-dependent oxidative stress and PKC signaling pathway. Neurosignals 14:46–60

    Article  CAS  PubMed  Google Scholar 

  40. Svilar D, Goellner EM, Almeida KH, Sobol RW (2011) Base excision repair and lesion-dependent subpathways for repair of oxidative DNA damage. Antioxid Redox Signal 14:2491–507

    Article  CAS  PubMed  Google Scholar 

  41. Fukui H, Moraes CT (2008) The mitochondrial impairment, oxidative stress and neurodegeneration connection: reality or just an attractive hypothesis? Trends Neurosci 31:251–6

    Article  CAS  PubMed  Google Scholar 

  42. Fukui H, Moraes CT (2009) Mechanisms of formation and accumulation of mitochondrial DNA deletions in aging neurons. Hum Mol Genet 18:1028–36

    Article  CAS  PubMed  Google Scholar 

  43. Virmani MA, Biselli R, Spadoni A, Rossi S, Corsico N, Calvani M, Fattorossi A, De Simone C, Arrigoni-Martelli E (1995) Protective actions of l-carnitine and acetyl-l-carnitine on the neurotoxicity evoked by mitochondrial uncoupling or inhibitors. Pharmacol Res 32:383–9

    Article  CAS  PubMed  Google Scholar 

  44. Hauser DN, Hastings TG (2013) Mitochondrial dysfunction and oxidative stress in Parkinson’s disease and monogenic parkinsonism. Neurobiol Dis 51:35–42

    Article  CAS  PubMed  Google Scholar 

  45. Pickrell AM, Fukui H, Moraes CT (2009) The role of cytochrome c oxidase deficiency in ROS and amyloid plaque formation. J Bioenerg Biomembr 41:453–6

    Article  CAS  PubMed  Google Scholar 

  46. Mahad D, Ziabreva I, Lassmann H, Turnbull D (2008) Mitochondrial defects in acute multiple sclerosis lesions. Brain 131:1722–35

    Article  PubMed  Google Scholar 

  47. Mahad D, Ziabreva I, Campbell G, Lax N, Hanson PS, Lassmann H, Turnbull DH (2009) Mitochondrial changes within axons in multiple sclerosis. Brain 132:1161–74

    Article  PubMed  Google Scholar 

  48. Higgins GC, Beart PM, Shin YS, Chen MJ, Cheung NS, Nagley P (2010) Oxidative stress: emerging mitochondrial and cellular themes and variations in neuronal injury. J Alzheimers Dis 20:453–73

    Google Scholar 

  49. Lu F, Selak M, O’Connor J, Croul S, Lorenzana C, Butunoi C, Kalman B (2000) Oxidative damage to mitochondrial DNA and activity of mitochondrial enzymes in chronic active lesions of multiple sclerosis. J Neurol Sci 177:95–103

    Article  CAS  PubMed  Google Scholar 

  50. Kalman B, Leist TP (2003) A mitochondrial component of neurodegeneration in multiple sclerosis. Neuromolecular Med 3:147–58

    Article  CAS  PubMed  Google Scholar 

  51. Mao P, Reddy PH (2010) Is multiple sclerosis a mitochondrial disease? Biochim Biophys Acta 1802:66–79

    Article  CAS  PubMed  Google Scholar 

  52. van Horssen J, Schreibelt G, Drexhage J, Hazes T, Dijkstra CD, van der Valk P, de Vries HE (2008) Severe oxidative damage in multiple sclerosis lesions coincides with enhanced antioxidant enzyme expression. Free Radic Biol Med 45:1729–37

    Article  PubMed  Google Scholar 

  53. Vladimirova O, O’Connor J, Cahill A, Alder H, Butunoi C, Kalman B (1998) Oxidative damage to DNA in plaques of MS brains. Mult Scler 4:413–8

    CAS  PubMed  Google Scholar 

  54. Smith KJ, Kapoor R, Felts PA (1999) Demyelination: the role of reactive oxygen and nitrogen species. Brain Pathol 9:69–92

    Article  CAS  PubMed  Google Scholar 

  55. Bizzozero OA, DeJesus G, Callahan K, Pastuszyn A (2005) Elevated protein carbonylation in the brain white matter and gray matter of patients with multiple sclerosis. J Neurosci Res 81:687–95

    Article  CAS  PubMed  Google Scholar 

  56. Qin J, Goswami R, Balabanov R, Dawson G (2007) Oxidized phosphatidylcholine is a marker for neuroinflammation in multiple sclerosis brain. J Neurosci Res 85:977–84

    Article  CAS  PubMed  Google Scholar 

  57. Farinotti M, Vacchi L, Simi S, Di Pietrantonj C, Brait L, Filippini G (2012) Dietary interventions for multiple sclerosis. Cochrane Database Syst Rev 12, CD004192

    PubMed  Google Scholar 

  58. Virmani A, Binienda Z (2004) Role of carnitine esters in brain neuropathology. Mol Aspects Med 25:533–4

    Article  CAS  PubMed  Google Scholar 

  59. Ramassamy C (2006) Emerging role of polyphenolic compounds in the treatment of neurodegenerative diseases: a review of their intracellular targets. Eur J Pharmacol 545:51–64

    Article  CAS  PubMed  Google Scholar 

  60. Virmani A, Gaetani F, Binienda Z (2005) Effects of metabolic modifiers such as carnitines, coenzyme Q10, and PUFAs against different forms of neurotoxic insults: metabolic inhibitors, MPTP, and methamphetamine. Ann N Y Acad Sci 1053:183–91

    Article  CAS  PubMed  Google Scholar 

  61. Topcu-Tarladacalisir Y, Kanter M, Uzal MC (2009) Role of l-carnitine in the prevention of seminiferous tubules damage induced by gamma radiation: a light and electron microscopic study. Arch Toxicol 83:735–46

    Article  CAS  PubMed  Google Scholar 

  62. Gülçin I (2006) Antioxidant and antiradical activities of l-carnitine. Life Sci 78:803–11

    Article  PubMed  Google Scholar 

  63. Calabrese V, Guagliano E, Sapienza M, Panebianco M, Calafato S, Puleo E, Pennisi G, Mancuso C, Butterfield DA, Stella AG (2007) Redox regulation of cellular stress response in aging and neurodegenerative disorders: role of vitagenes. Neurochem Res 32:757–73

    Article  CAS  PubMed  Google Scholar 

  64. Suchitra MM, Ashalatha VL, Sailaja E, Rao AM, Reddy VS, Bitla AR, Sivakumar V, Rao PV (2011) The effect of l-carnitine supplementation on lipid parameters, inflammatory and nutritional markers in maintenance hemodialysis patients. Saudi J Kidney Dis Transpl 22:1155–9

    CAS  PubMed  Google Scholar 

  65. Perez-De La Cruz V, Santamaria A (2007) Integrative hypothesis for Huntington’s disease: a brief review of experimental evidence. Physiol Res 56:513–26

    CAS  PubMed  Google Scholar 

  66. Shen W, Liu K, Tian C, Yang L, Li X, Ren J, Packer L, Cotman CW, Liu J (2008) R-alpha-lipoic acid and acetyl-l-carnitine complementarily promote mitochondrial biogenesis in murine 3T3-L1 adipocytes. Diabetologia 51:165–74

    Article  CAS  PubMed  Google Scholar 

  67. Silva-Adaya D, Pérez-De La Cruz V, Herrera-Mundo MN, Mendoza-Macedo K, Villeda-Hernández J, Binienda Z, Ali SF, Santamaría A (2008) Excitotoxic damage, disrupted energy metabolism, and oxidative stress in the rat brain: antioxidant and neuroprotective effects of l-carnitine. J Neurochem 105:677–89

    Article  CAS  PubMed  Google Scholar 

  68. Beher D, Wu J, Cumine S, Kim KW, Lu SC, Atangan L, Wang M (2009) Resveratrol is not a direct activator of SIRT1 enzyme activity. Chem Biol Drug Des 74:619–24

    Article  CAS  PubMed  Google Scholar 

  69. Pacholec M, Bleasdale JE, Chrunyk B, Cunningham D, Flynn D, Garofalo RS, Griffith D, Griffor M, Loulakis P, Pabst B, Qiu X, Stockman B, Thanabal V, Varghese A, Ward J, Withka J, Ahn K (2010) SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1. J Biol Chem 285:8340–51

    Article  CAS  PubMed  Google Scholar 

  70. Wareski P, Vaarmann A, Choubey V, Safiulina D, Liiv J, Kuum M, Kaasik A (2009) PGC-1{alpha} and PGC-1{beta} regulate mitochondrial density in neurons. J Biol Chem 284:21379–85

    Article  CAS  PubMed  Google Scholar 

  71. Wang K, Lee I, Carlson G, Hood L, Galas D (2010) Systems biology and the discovery of diagnostic biomarkers. Dis Markers 28:199–207

    Article  CAS  PubMed  Google Scholar 

  72. Buonaguro L, Pulendran B (2011) Immunogenomics and systems biology of vaccines. Immunol Rev 239:197–208

    Article  CAS  PubMed  Google Scholar 

  73. Buonaguro L, Wang E, Tornesello ML, Buonaguro FM, Marincola FM (2011) Systems biology applied to vaccine and immunotherapy development. BMC Syst Biol 5:146

    Article  CAS  PubMed  Google Scholar 

  74. Aderem A, Adkins JN, Ansong C, Galagan J, Kaiser S, Korth MJ, Law GL, McDermott JG, Proll SC, Rosenberger C, Schoolnik G, Katze MG (2011) A systems biology approach to infectious disease research: innovating the pathogen–host research paradigm. MBio 2:e00325–10

    Article  PubMed  Google Scholar 

  75. Müller M, Kersten S (2003) Nutrigenomics: goals and strategies. Nat Rev Genet 4:315–22

    Article  PubMed  Google Scholar 

  76. Kapka-Skrzypczak L, Niedzwiecka J, Cyranka M, Kruszewski MK, Skrzypczak M, Wojtyla A (2011) Nutrigenomics—perspectives of personalized nutrition. Pediatr Endocrinol Diabetes Metab 17:222–6

    PubMed  Google Scholar 

  77. García-Cañas V, Simó C, León C, Cifuentes A (2010) Advances in nutrigenomics research: novel and future analytical approaches to investigate the biological activity of natural compounds and food functions. J Pharm Biomed Anal 51:290–304

    Article  PubMed  Google Scholar 

  78. Raqib R, Cravioto R (2009) Nutrition, immunology, and genetics: future perspectives. Nutr Rev 67:S227–36

    Article  PubMed  Google Scholar 

  79. Wittwer J, Rubio-Aliaga I, Hoeft B, Bendik I, Weber P, Daniel H (2011) Nutrigenomics in human intervention studies: current status, lessons learned and future perspectives. Mol Nutr Food Res 55:341–58

    Article  CAS  PubMed  Google Scholar 

  80. Harrow J et al (2012) GENCODE: the reference human genome annotation for The ENCODE Project. Genome Res 22:1760–74

    Article  CAS  PubMed  Google Scholar 

  81. ENCODE Project Consortium, Bernstein BE, Birney E, Dunham I, Green ED, Gunter C, Snyder M (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489:57–74

    Article  PubMed  Google Scholar 

  82. Trujillo E, Davis C, Milner J (2006) Nutrigenomics, proteomics, metabolomics, and the practice of dietetics. J Am Diet Assoc 106:403–13

    Article  CAS  PubMed  Google Scholar 

  83. Madiraju P, Pande SV, Prentki M, Madiraju SR (2009) Mitochondrial acetylcarnitine provides acetyl groups for nuclear histone acetylation. Epigenetics 4:399–403

    Article  CAS  PubMed  Google Scholar 

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Virmani, A., Pinto, L., Binienda, Z. et al. Food, Nutrigenomics, and Neurodegeneration—Neuroprotection by What You Eat!. Mol Neurobiol 48, 353–362 (2013). https://doi.org/10.1007/s12035-013-8498-3

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