The importance of NAD in multiple sclerosis

Current Pharmaceutical Design

Volumn 15, Issue 1, 2009, Pages 64-99

  Penberthy, W Todd ^a   Tsunoda, Ikuo ^b  

^a UNIVERSITY OF CINCINNATI COLLEGE OF MEDICINE   (United States)

^b UNIVERSITY OF UTAH SCHOOL OF MEDICINE   (United States)

Author keywords

ADP cyclase; CD200; Indoleamine 2,3 dioxygenase; Multiple sclerosis; Nicotinamide adenine dinucleotide; PARP 1; SIRT1; Wallerian degeneration

Indexed keywords

1 METHYLTRYPTOPHAN; 2,2' DIHYDROXYAZOBENZENE; CD38 ANTIGEN; DIHYDROXYAZOBENZENE; ENZYME INHIBITOR; GAMMA INTERFERON; INDOLEAMINE 2,3 DIOXYGENASE; INDOLEAMINE 2,3 DIOXYGENASE INHIBITOR; MINOCYCLINE; N (5,6 DIHYDRO 6 OXO 2 PHENANTHRIDINYL) 2 DIMETHYLAMINOACETAMIDE; NICOTINAMIDE; NICOTINAMIDE ADENINE DINUCLEOTIDE; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE 1; NICOTINAMIDE NUCLEOTIDE; NICOTINAMIDE NUCLEOTIDE ADENYLYLTRANSFERASE; NICOTINAMIDE NUCLEOTIDE ADENYLYLTRANSFERASE 1; NICOTINAMIDE RIBOSIDE; NICOTINIC ACID; RESVERATROL; SIRTUIN 1; SRT 501; SRT 647; UNCLASSIFIED DRUG; VORINOSTAT;

ALLERGIC ENCEPHALOMYELITIS; BLOOD BRAIN BARRIER; DEMYELINATION; DRUG MEGADOSE; ENZYME ACTIVITY; ENZYME BLOOD LEVEL; ENZYME DEGRADATION; ENZYME SYNTHESIS; GLIA CELL; HUMAN; IMMUNE RESPONSE; IMMUNOPATHOLOGY; LUPUS VULGARIS; MULTIPLE SCLEROSIS; NERVE CELL; NERVE DEGENERATION; NERVE FIBER DEGENERATION; NEUROPROTECTION; NONHUMAN; OPTIC NEURITIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW; SIGNAL TRANSDUCTION; ANIMAL; IMMUNOLOGY; METABOLISM; MOUSE;

ANIMALS; HUMANS; MICE; MULTIPLE SCLEROSIS; NAD;

EID: 62149128630     PISSN: 13816128     EISSN: None     Source Type: Journal    
DOI: 10.2174/138161209787185751     Document Type: Review

References (346)

1. Bogan KL, Brenner C. Nicotinic acid, nicotinamide, and nicotinamide riboside: A molecular evaluation of NAD(+) precursor vitamins in human nutrition. Annu Rev Nutr 2008; 28: 115-30.
2. Tang K, Sham H, Hui E, Kirkland JB. Niacin deficiency causes oxidative stress in rat bone marrow cells but not through decreased NADPH or glutathione status. J Nutr Biochem 2008; [Epub ahead of print].
3. Belenky P, Bogan KL, Brenner C. NAD+ metabolism in health and disease. Trends Biochem Sci 2007; 32: 12-9.
4. Khan JA, Forouhar F, Tao X, Tong L. Nicotinamide adenine dinucleotide metabolism as an attractive target for drug discovery. Expert Opin Ther Targets 2007; 11: 695-705.
5. Etheridge EW. The butterfly caste: A social history of pellagra in the South, Greenwood Pub. Co: Westport, Conn; 1972.
6. Park YK, Sempos CT, Barton CN, Vanderveen JE, Yetley EA. Effectiveness of food fortification in the United States: The case of pellagra. Am J Public Health 2000; 90: 727-38.
7. Kaneko S, Wang J, Kaneko M, Yiu G, Hurrell JM, Chitnis T, et al. Protecting axonal degeneration by increasing nicotinamide adenine dinucleotide levels in experimental autoimmune encephalomyelitis models. J Neurosci 2006; 26: 9794-804.
8. Tempel W, Rabeh WM, Bogan KL, Belenky P, Wojcik M, Seidle HF, et al. Nicotinamide riboside kinase structures reveal new pathways to NAD+. PLoS Biol 2007; 5: E263.
9. Chiarugi A. Inhibitors of poly(ADP-ribose) polymerase-1 suppress transcriptional activation in lymphocytes and ameliorate autoimmune encephalomyelitis in rats. Br J Pharmacol 2002; 137: 761-70.
10. Ott M, Demisch L, Engelhardt W, Fischer PA. Interleukin-2, soluble interleukin-2-receptor, neopterin, L-tryptophan and beta 2-microglobulin levels in CSF and serum of patients with relapsing-remitting or chronic-progressive multiple sclerosis. J Neurol 1993; 241: 108-14.
11. Chen D, Bruno J, Easlon E, Lin SJ, Cheng HL, Alt FW, et al. Tissue-specific regulation of SIRT1 by calorie restriction. Genes Dev 2008.
12. Esquifino AI, Cano P, Jimenez V, Cutrera RA, Cardinali DP. Experimental allergic encephalomyelitis in male Lewis rats subjected to calorie restriction. J Physiol Biochem 2004; 60: 245-52.
13. Piccio L, Stark JL, Cross AH. Chronic calorie restriction attenuates experimental autoimmune encephalomyelitis. J Leukoc Biol 2008.
14. Esquifino AI, Cano P, Jimenez-Ortega V, Fernandez-Mateos MP, Cardinali DP. Immune response after experimental allergic encephalomyelitis in rats subjected to calorie restriction. J Neuroinflammation 2007; 4: 6.
15. Fulco M, Cen Y, Zhao P, Hoffman EP, McBurney MW, Sauve AA, et al. Glucose restriction inhibits skeletal myoblast differentiation by activating SIRT1 through AMPK-mediated regulation of Nampt. Dev Cell 2008; 14: 661-73.
16. Boily G, Seifert EL, Bevilacqua L, He XH, Sabourin G, Estey C, et al. SIRT1 regulates energy metabolism and response to caloric restriction in mice. PLoS ONE 2008; 3: E1759.
17. Revollo JR, Grimm AA, Imai S. The NAD biosynthesis pathway mediated by nicotinamide phosphoribosyltransferase regulates Sir2 activity in mammalian cells. J Biol Chem 2004; 279: 50754-63.
18. Lamming DW, Wood JG, Sinclair DA. Small molecules that regulate lifespan: Evidence for xenohormesis. Mol Microbiol 2004; 53: 1003-9
19. Wacker DA, Ruhl DD, Balagamwala EH, Hope KM, Zhang T, Kraus WL. The DNA binding and catalytic domains of poly(ADP-ribose) polymerase 1 cooperate in the regulation of chromatin structure and transcription. Mol Cell Biol 2007; 27: 7475-85.
20. Miller CL, Llenos IC, Dulay JR, Barillo MM, Yolken RH, Weis S. Expression of the kynurenine pathway enzyme tryptophan 2,3-dioxygenase is increased in the frontal cortex of individuals with schizophrenia. Neurobiol Dis 2004; 15: 618-29.
21. Mellor AL, Munn DH. IDO expression by dendritic cells: Tolerance and tryptophan catabolism. Nat Rev Immunol 2004; 4: 762-74.
22. Guillemin GJ, Cullen KM, Lim CK, Smythe GA, Garner B, Kapoor V, et al. Characterization of the kynurenine pathway in human neurons. J Neurosci 2007; 27: 12884-92.
23. Grant RS, Passey R, Matanovic G, Smythe G, Kapoor V. Evidence for increased de novo synthesis of NAD in immune-activated RAW264.7 macrophages: A self-protective mechanism? Arch Biochem Biophys 1999; 372: 1-7.
24. Kujundzic RN, Lowenthal JW. The role of tryptophan metabolism in iNOS transcription and nitric oxide production by chicken macrophage cells upon treatment with interferon gamma. Immunol Lett 2008; 115: 153-9.
25. Grant RS, Naif H, Espinosa M, Kapoor V. IDO induction in IFN-gamma activated astroglia: A role in improving cell viability during oxidative stress. Redox Rep 2000; 5: 101-4.
26. Grant R, Kapoor V. Inhibition of indoleamine 2,3-dioxygenase activity in IFN-gamma stimulated astroglioma cells decreases intracellular NAD levels. Biochem Pharmacol 2003; 66: 1033-6.
27. Sasaki Y, Araki T, Milbrandt J. Stimulation of nicotinamide adenine dinucleotide biosynthetic pathways delays axonal degeneration after axotomy. J Neurosci 2006; 26: 8484-91.
28. Suh SW, Hamby AM, Swanson RA. Hypoglycemia, brain energetics, and hypoglycemic neuronal death. Glia 2007; 55: 1280-6.
29. Munn DH, Shafizadeh E, Attwood JT, Bondarev I, Pashine A, Mellor AL. Inhibition of T cell proliferation by macrophage tryptophan catabolism. J Exp Med 1999; 189: 1363-72.
30. Munn DH, Sharma MD, Mellor AL. Ligation of B7-1/B7-2 by human CD4+ T cells triggers indoleamine 2,3-dioxygenase activity in dendritic cells. J Immunol 2004; 172: 4100-10.
31. Sakurai K, Zou JP, Tschetter JR, Ward JM, Shearer GM. Effect of indoleamine 2,3-dioxygenase on induction of experimental autoimmune encephalomyelitis. J Neuroimmunol 2002; 129: 186-96.
32. Kwidzinski E, Bunse J, Kovac AD, Ullrich O, Zipp F, Nitsch R, et al. IDO (indolamine 2,3-dioxygenase) expression and function in the CNS. Adv Exp Med Biol 2003; 527: 113-8.
33. Kwidzinski E, Bunse J, Aktas O, Richter D, Mutlu L, Zipp F, et al. Indolamine 2,3-dioxygenase is expressed in the CNS and downregulates autoimmune inflammation. Faseb J 2005; 19: 1347-9.
34. Matysiak M, Stasiolek M, Orlowski W, Jurewicz A, Janczar S, Raine CS, et al. Stem cells ameliorate EAE via an indoleamine 2,3-dioxygenase (IDO) mechanism. J Neuroimmunol 2008; 193: 12-23.
35. Ruddick JP, Evans AK, Nutt DJ, Lightman SL, Rook GA, Lowry CA. Tryptophan metabolism in the central nervous system: Medical implications. Expert Rev Mol Med 2006; 8: 1-27.
36. Araki T, Sasaki Y, Milbrandt J. Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration. Science 2004; 305: 1010-3.
37. Wang J, Zhai Q, Chen Y, Lin E, Gu W, McBurney MW, et al. A local mechanism mediates NAD-dependent protection of axon degeneration. J Cell Biol 2005; 170: 349-55.
38. Stevens MJ, Li F, Drel V, Abatan O, Kim H, Burnett D, et al. Nicotinamde reverses neurological and neurovascular deficits in streptozotocin diabetic rats. J Pharmacol Exp Ther 2006; 320(1): 458-64.
39. Lee EJ, Wu TS, Chang GL, Li CY, Chen TY, Lee MY, et al. Delayed treatment with nicotinamide inhibits brain energy depletion, improves cerebral microperfusion, reduces brain infarct volume, but does not alter neurobehavioral outcome following permanent focal cerebral ischemia in Sprague Dawley rats. Curr Neurovasc Res 2006; 3: 203-13.
40. Ayoub IA, Maynard KI. Therapeutic window for nicotinamide following transient focal cerebral ischemia. Neuroreport 2002; 13: 213-6.
41. Sakakibara Y, Mitha AP, Ogilvy CS, Maynard KI. Post-treatment with nicotinamide (vitamin B(3)) reduces the infarct volume following permanent focal cerebral ischemia in female Sprague-Dawley and Wistar rats. Neurosci Lett 2000; 281: 111-4.
42. Li F, Chong ZZ, Maiese K. Navigating novel mechanisms of cellular plasticity with the NAD+ precursor and nutrient nicotinamide. Front Biosci 2004; 9: 2500-20.
43. Grant RS, Kapoor V. Murine glial cells regenerate NAD, after peroxide-induced depletion, using either nicotinic acid, nicotinamide, or quinolinic acid as substrates. J Neurochem 1998; 70: 1759-63.
44. Lu H, Burns D, Garnier P, Wei G, Zhu K, Ying W. P2X7 receptors mediate NADH transport across the plasma membranes of astrocytes. Biochem Biophys Res Commun 2007; 362: 946-50.
45. Lu H, Swanson RA, Ying W. American Society for Neurosciences Annual Meeting; 2006.
46. Barres BA, Smith SJ. Neurobiology. Cholesterol - making or breaking the synapse. Science 2001; 294: 1296-7.
47. Ishii N, Nishihara Y. Pellagra among chronic alcoholics: Clinical and pathological study of 20 necropsy cases. J Neurol Neurosurg Psychiatry 1981; 44: 209-15.
48. Ying W, Wei G, Wang D, Wang Q, Tang X, Shi J, et al. Intranasal administration with NAD+ profoundly decreases brain injury in a rat model of transient focal ischemia. Front Biosci 2007; 12: 2728-34.
49. Ying W. NAD+ and NADH in Neuronal Death. J Neuroimmune Pharmacol 2007; 2: 270-5.
50. Pellerin L, Bouzier-Sore AK, Aubert A, Serres S, Merle M, Costalat R, et al. Activity-dependent regulation of energy metabolism by astrocytes: An update. Glia 2007; 55: 1251-62.
51. Bergersen LH. Is lactate food for neurons? Comparison of monocarboxylate transporter subtypes in brain and muscle. Neuroscience 2007; 145: 11-9.
52. Carson MJ, Anglen CS, Ploix C. In: Minagar A, Alexander JS, Eds. Multiple sclerosis. A disease of miscommunication between the immune and central nervous systems?, Humana Press Inc.: Totwa, New Jersey 2005; pp. 17-39.
53. Lassmann H. Models of multiple sclerosis: New insights into pathophysiology and repair. Curr Opin Neurol 2008; 21: 242-7.
54. Bitsch A, Bruck W. Differentiation of multiple sclerosis subtypes: implications for treatment. CNS Drugs 2002; 16: 405-18.
55. Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG. Multiple sclerosis. N Engl J Med 2000; 343: 938-52.
56. Lublin FD, Reingold SC. Defining the clinical course of multiple sclerosis: Results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology 1996; 46: 907-11.
57. Peltonen L. Old suspects found guilty - the first genome profile of multiple sclerosis. N Engl J Med 2007; 357: 927-9.
58. Brown SJ. The role of vitamin D in multiple sclerosis. Ann Pharmacother 2006; 40: 1158-61.
59. Kira J, Tobimatsu S, Goto I. Vitamin B12 metabolism and massive-dose methyl vitamin B12 therapy in Japanese patients with multiple sclerosis. Intern Med 1994; 33: 82-6.
60. Miller A, Korem M, Almog R, Galboiz Y. Vitamin B12, demyelination, remyelination and repair in multiple sclerosis. J Neurol Sci 2005; 233: 93-7.
61. Reynolds EH, Linnell JC. Vitamin B12 deficiency, demyelination, and multiple sclerosis. Lancet 1987; 2: 920.
62. Baethmann M, Wendel U, Hoffmann GF, Gohlich-Ratmann G, Kleinlein B, Seiffert P, et al. Hydrocephalus internus in two patients with 5,10-methylenetetrahydrofolate reductase deficiency. Neuropediatrics 2000; 31: 314-7.
63. Kishi T, Tanaka Y, Ueda K. Evidence for hypomethylation in two children with acute lymphoblastic leukemia and leukoencephalopathy. Cancer 2000; 89: 925-31.
64. Simmons A. Herpesvirus and multiple sclerosis. Herpes 2001; 8: 60-3.
65. Panitch HS, Hirsch RL, Haley AS, Johnson KP. Exacerbations of multiple sclerosis in patients treated with gamma interferon. Lancet 1987; 1: 893-5.
66. Panitch HS, Hirsch RL, Schindler J, Johnson KP. Treatment of multiple sclerosis with gamma interferon: Exacerbations associated with activation of the immune system. Neurology 1987; 37: 1097-102.
67. Jacobs LD, Beck RW, Simon JH, Kinkel RP, Brownscheidle CM, Murray TJ, et al. Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. CHAMPS Study Group. N Engl J Med 2000; 343: 898-904.
68. Kappos L, Freedman MS, Polman CH, Edan G, Hartung HP, Miller DH, et al. Effect of early versus delayed interferon beta-1b treatment on disability after a first clinical event suggestive of multiple sclerosis: A 3-year follow-up analysis of the BENEFIT study. Lancet 2007; 370: 389-97.
69. Rodriguez M, Zoecklein LJ, Howe CL, Pavelko KD, Gamez JD, Nakane S, et al. Gamma interferon is critical for neuronal viral clearance and protection in a susceptible mouse strain following early intracranial Theiler's murine encephalomyelitis virus infection. J Virol 2003; 77: 12252-65.
70. Adams O, Besken K, Oberdorfer C, MacKenzie CR, Russing D, Daubener W. Inhibition of human herpes simplex virus type 2 by interferon gamma and tumor necrosis factor alpha is mediated by indoleamine 2,3-dioxygenase. Microbes Infect 2004; 6: 806-12.
71. Adams O, Besken K, Oberdorfer C, MacKenzie CR, Takikawa O, Daubener W. Role of indoleamine-2,3-dioxygenase in alpha/beta and gamma interferon-mediated antiviral effects against herpes simplex virus infections. J Virol 2004; 78: 2632-6.
72. Bodaghi B, Goureau O, Zipeto D, Laurent L, Virelizier JL, Michelson S. Role of IFN-gamma-induced indoleamine 2,3 dioxygenase and inducible nitric oxide synthase in the replication of human cytomegalovirus in retinal pigment epithelial cells. J Immunol 1999; 162: 957-64.
73. Sanni LA, Thomas SR, Tattam BN, Moore DE, Chaudhri G, Stocker R, et al. Dramatic changes in oxidative tryptophan metabolism along the kynurenine pathway in experimental cerebral and noncerebral malaria. Am J Pathol 1998; 152: 611-9.
74. MacKenzie CR, Hadding U, Daubener W. Interferon-gamma-induced activation of indoleamine 2,3-dioxygenase in cord blood monocyte-derived macrophages inhibits the growth of group B streptococci. J Infect Dis 1998; 178: 875-8.
75. Pfefferkorn ER. Interferon gamma blocks the growth of Toxoplasma gondii in human fibroblasts by inducing the host cells to degrade tryptophan. Proc Natl Acad Sci USA 1984; 81: 908-12.
76. Silva NM, Rodrigues CV, Santoro MM, Reis LF, Alvarez-Leite JI, Gazzinelli RT. Expression of indoleamine 2,3-dioxygenase, tryptophan degradation, and kynurenine formation during in vivo infection with Toxoplasma gondii: Induction by endogenous gamma interferon and requirement of interferon regulatory factor 1. Infect Immun 2002; 70: 859-68.
77. Byrne GI, Lehmann LK, Landry GJ. Induction of tryptophan catabolism is the mechanism for gamma-interferon-mediated inhibition of intracellular Chlamydia psittaci replication in T24 cells. Infect Immun 1986; 53: 347-51.
78. Owens T. Animal models for multiple sclerosis. Adv Neurol 2006; 98: 77-89.
79. Tsunoda I, Fujinami RS. Two models for multiple sclerosis: Experimental allergic encephalomyelitis and Theiler's murine encephalomyelitis virus. J Neuropathol Exp Neurol 1996; 55: 673-86.
80. Tsunoda I, Kuang LQ, Tolley ND, Whitton JL, Fujinami RS. Enhancement of experimental allergic encephalomyelitis (EAE) by DNA immunization with myelin proteolipid protein (PLP) plasmid DNA. J Neuropathol Exp Neurol 1998; 57: 758-67.
81. s mouse strains. Brain Pathol 2000; 10: 402-18.
82. Tsunoda I, Fujinami RS. In: Lavi E, Constantinescu CS, Eds. Experimental Models of Multiple Sclerosis. TMEV and neuroantigens: Myelin genes and proteins, molecular mimicry, epitope spreading and autoantibody-mediated remyelination. New York, N.Y., 2005, pp. 593-616.
83. Tsunoda I, Lane TE, Blackett J, Fujinami RS. Distinct roles for IP-10/ CXCL10 in three animal models, Theiler's virus infection, EAE, and MHV infection, for multiple sclerosis: Implication of differing roles for IP-10. Mult Scler 2004; 10: 26-34.
84. Raff MC, Barres BA, Burne JF, Coles HS, Ishizaki Y, Jacobson MD. Programmed cell death and the control of cell survival: Lessons from the nervous system. Science 1993; 262: 695-700.
85. Lunn ER, Perry VH, Brown MC, Rosen H, Gordon S. Absence of Wallerian Degeneration does not Hinder Regeneration in Peripheral Nerve. Eur J Neurosci 1989; 1: 27-33.
86. Coleman MP, Perry VH. Axon pathology in neurological disease: A neglected therapeutic target. Trends Neurosci 2002; 25: 532-7.
87. Gillingwater TH, Wishart TM, Chen PE, Haley JE, Robertson K, MacDonald SH, et al. The neuroprotective WldS gene regulates expression of PTTG1 and erythroid differentiation regulator 1-like gene in mice and human cells. Hum Mol Genet 2006; 15: 625-35.
88. Ludwin SK, Bisby MA. Delayed Wallerian degeneration in the central nervous system of Ola mice: An ultrastructural study. J Neurol Sci 1992; 109: 140-7.
89. Perry VH, Lunn ER, Brown MC, Cahusac S, Gordon S. Evidence that the rate of wallerian degeneration is controlled by a single autosomal dominant gene. Eur J Neurosci 1990; 2: 408-413.
90. Glass JD, Griffin JW. Neurofilament redistribution in transected nerves: evidence for bidirectional transport of neurofilaments. Neurosci 1991; 11: 3146-54.
91. Glass JD, Griffin JW. Retrograde transport of radiolabeled cytoskeletal proteins in transected nerves. J Neurosci 1994; 14: 3915-21.
92. Watson DF, Glass JD, Griffin JW. Redistribution of cytoskeletal proteins in mammalian axons disconnected from their cell bodies. Neurosci 1993; 13: 4354-60.
93. Koike T, Yang Y, Suzuki K, Zheng X. Axon & dendrite degeneration: Its mechanisms and protective experimental paradigms. Neurochem Int 2008; 52: 751-60.
94. Mack TG, Reiner M, Beirowski B, Mi W, Emanuelli M, Wagner D, et al. Wallerian degeneration of injured axons and synapses is delayed by a Ube4b/Nmnat chimeric gene. Nat Neurosci 2001; 4: 1199-206.
95. Fainzilber M, Twiss JL. Tracking in the Wlds - the hunting of the SIRT and the luring of the Draper. Neuron 2006; 50: 819-21.
96. Chong ZZ, Lin SH, Maiese K. The NAD+ precursor nicotinamide governs neuronal survival during oxidative stress through protein kinase B coupled to FOXO3a and mitochondrial membrane potential. J Cereb Blood Flow Metab 2004; 24: 728-43.
97. Chitnis T, Imitola J, Wang Y, Elyaman W, Chawla P, Sharuk M, et al. Elevated neuronal expression of CD200 protects Wlds mice from inflammation-mediated neurodegeneration. Am J Pathol 2007; 170: 1695-712.
98. Tsunoda I, Tanaka T, Terry EJ, Fujinami RS. Contrasting roles for axonal degeneration in an autoimmune versus viral model of multiple sclerosis: When can axonal injury be beneficial? Am J Pathol 2007; 170: 214-26
99. Tsunoda I, Terry EJ, Marble BJ, Lazarides E, Woods C, Fujinami RS. Modulation of experimental autoimmune encephalomyelitis by VLA-2 blockade. Brain Pathol 2007; 17: 45-55.
100. Aswad F, Kawamura H, Dennert G. High sensitivity of CD4+CD25+ regulatory T cells to extracellular metabolites nicotinamide adenine dinucleotide and ATP: A role for P2X7 receptors. Immunol 2005; 175: 3075-83.
101. Kawamura H, Aswad F, Minagawa M, Malone K, Kaslow H, Koch-Nolte F, et al. P2X7 receptor-dependent and -independent T cell death is induced by nicotinamide adenine dinucleotide. J Immunol 2005; 174: 1971-9.
102. Fallarino F, Asselin-Paturel C, Vacca C, Bianchi R, Gizzi S, Fioretti MC, et al. Murine plasmacytoid dendritic cells initiate the immunosuppressive pathway of tryptophan catabolism in response to CD200 receptor engagement. J Immunol 2004; 173: 3748-54. 103 Piccio L, Buonsanti C, Cella M, Tassi I, Schmidt RE, Fenoglio C, et al. Identification of soluble TREM-2 in the cerebrospinal fluid and its association with multiple sclerosis and CNS inflammation. Brain 2008.
103. Shindler KS, Ventura E, Rex TS, Elliott P, Rostami A. SIRT1 activation confers neuroprotection in experimental optic neuritis. Invest Ophthalmol Vis Sci 2007; 48: 3602-9.
104. Suzuki K, Koike T. Resveratrol abolishes resistance to axonal degeneration in slow Wallerian degeneration (WldS) mice: Activation of SIRT2, an NAD-dependent tubulin deacetylase. Biochem Biophys Res Commun 2007; 359: 665-71.
105. Tsunoda I. Axonal degeneration as a self-destructive defense mechanism against neurotropic virus infection. Future Virol 2008; 3: 579-593.
106. Roussarie JP, Ruffie C, Edgar JM, Griffiths I, Brahic M. Axon myelin transfer of a non-enveloped virus. PLoS ONE 2007; 2: E1331.
107. Taylor MP, Kirkegaard K. Potential subversion of autophagosomal pathway by picornaviruses. Autophagy 2008; 4: 286-9.
108. Chiarugi A. Intrinsic mechanisms of poly(ADP-ribose) neurotoxicity: three hypotheses. Neurotoxicology 2005; 26: 847-55.
109. Kolthur-Seetharam U, Dantzer F, McBurney MW, de Murcia G, Sassone-Corsi P. Control of AIF-mediated cell death by the functional interplay of SIRT1 and PARP-1 in response to DNA damage. Cell Cycle 2006; 5: 873-7
110. Pillai JB, Gupta M, Rajamohan SB, Lang R, Raman J, Gupta MP. Poly(ADP-ribose) polymerase-1-deficient mice are protected from angiotensin II-induced cardiac hypertrophy. Am J Physiol Heart Circ Physiol 2006; 291: H1545-53.
111. Pillai JB, Isbatan A, Imai S, Gupta MP. Poly(ADP-ribose) polymerase- 1-dependent cardiac myocyte cell death during heart failure is mediated by NAD+ depletion and reduced Sir2alpha deacetylase activity. J Biol Chem 2005; 280: 43121-30.
112. Jagtap P, Szabo C. Poly(ADP-ribose) polymerase and the therapeutic effects of its inhibitors. Nat Rev Drug Discov 2005; 4: 421-40.
113. Pacher P, Szabo C. Role of poly(ADP-ribose) polymerase 1 (PARP-1) in cardiovascular diseases: The therapeutic potential of PARP inhibitors. Cardiovasc Drug Rev 2007; 25: 235-60.
114. Cai AL, Zipfel GJ, Sheline CT. Zinc neurotoxicity is dependent on intracellular NAD levels and the sirtuin pathway. Eur J Neurosci 2006; 24: 2169-76.
115. Alano CC, Ying W, Swanson RA. Poly(ADP-ribose) polymerase- 1-mediated cell death in astrocytes requires NAD+ depletion and mitochondrial permeability transition. J Biol Chem 2004; 279: 18895-902.
116. Alano CC, Kauppinen TM, Valls AV, Swanson RA. Minocycline inhibits poly(ADP-ribose) polymerase-1 at nanomolar concentrations. Proc Natl Acad Sci USA 2006; 103: 9685-90.
117. Shall S, de Murcia G. Poly(ADP-ribose) polymerase-1: What have we learned from the deficient mouse model? Mutat Res 2000; 460: 1-15.
118. Ahn BH, Kim HS, Song S, Lee IH, Liu J, Vassilopoulos A, et al. A role for the mitochondrial deacetylase SIRT3 in regulating energy homeostasis. Proc Natl Acad Sci USA 2008.
119. Lombard DB, Alt FW, Cheng HL, Bunkenborg J, Streeper RS, Mostoslavsky R, et al. Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation. Mol Cell Biol 2007; 27: 8807-14.
120. Rayalam S, Yang JY, Ambati S, Della-Fera MA, Baile CA. Resveratrol induces apoptosis and inhibits adipogenesis in 3T3-L1 adipocytes. Phytother Res 2008; 22: 1367-1371.
121. Schrocksnadel K, Wirleitner B, Winkler C, Fuchs D. Monitoring tryptophan metabolism in chronic immune activation. Clin Chim Acta 2006; 364: 82-90.
122. Ball HJ, Yuasa HJ, Austin CJ, Weiser S, Hunt NH. Indoleamine 2,3-dioxygenase-2; a new enzyme in the kynurenine pathway. Int J Biochem Cell Biol 2008.
123. Ball HJ, Sanchez-Perez A, Weiser S, Austin CJ, Astelbauer F, Miu J, et al. Characterization of an indoleamine 2,3-dioxygenase-like protein found in humans and mice. Gene 2007; 396: 203-13.
124. Staykova MA, Linares D, Fordham SA, Paridaen JT, Willenborg DO. The innate immune response to adjuvants dictates the adaptive immune response to autoantigens. J Neuropathol Exp Neurol 2008; 67: 543-54.
125. Murray MF. The human indoleamine 2,3-dioxygenase gene and related human genes. Curr Drug Metab 2007; 8: 197-200.
126. Munn DH, Zhou M, Attwood JT, Bondarev I, Conway SJ, Marshall B, et al. Prevention of allogeneic fetal rejection by tryptophan catabolism. Science 1998; 281: 1191-3.
127. Miller CL, Llenos IC, Cwik M, Walkup J, Weis S. Alterations in kynurenine precursor and product levels in schizophrenia and bipolar disorder. Neurochem Int 2008; 52: 1297-303.
128. Osmond H, Hoffer A. Massive niacin treatment in schizophrenia. Review of a nine-year study. Lancet 1962; 1: 316-9.
129. Xiao BG, Liu X, Link H. Antigen-specific T cell functions are suppressed over the estrogen-dendritic cell-indoleamine 2,3- dioxygenase axis. Steroids 2004; 69: 653-9.
130. Zhu WH, Lu CZ, Huang YM, Link H, Xiao BG. A putative mechanism on remission of multiple sclerosis during pregnancy: Estrogen-induced indoleamine 2,3-dioxygenase by dendritic cells. Mult Scler 2007; 13: 33-40.
131. Grohmann U, Volpi C, Fallarino F, Bozza S, Bianchi R, Vacca C, et al. Reverse signaling through GITR ligand enables dexamethasone to activate IDO in allergy. Nat Med 2007; 13: 579-86.
132. Puccetti P, Grohmann U. IDO and regulatory T cells: A role for reverse signalling and non-canonical NF-kappaB activation. Nat Rev Immunol 2007; 7: 817-23.
133. Koenig JI, Kirkpatrick B, Lee P. Glucocorticoid hormones and early brain development in schizophrenia. Neuropsychopharmacology 2002; 27: 309-18.
134. Miller CL, Llenos IC, Dulay JR, Weis S. Upregulation of the initiating step of the kynurenine pathway in postmortem anterior cingulate cortex from individuals with schizophrenia and bipolar disorder. Brain Res 2006; 1073-1074: 25-37.
135. Iqbal J, Zaidi M. TNF regulates cellular NAD+ metabolism in primary macrophages. Biochem Biophys Res Commun 2006; 342: 1312-8.
136. Partida-Sanchez S, Gasser A, Fliegert R, Siebrands CC, Dammermann W, Shi G, et al. Chemotaxis of mouse bone marrow neutrophils and dendritic cells is controlled by adp-ribose, the major product generated by the CD38 enzyme reaction. J Immunol 2007; 179: 7827-39.
137. Mayo L, Jacob-Hirsch J, Amariglio N, Rechavi G, Moutin MJ, Lund FE, et al. Dual role of CD38 in microglial activation and activation-induced cell death. J Immunol 2008; 181: 92-103.
138. Franco L, Bodrato N, Moreschi I, Usai C, Bruzzone S, Scarf i S, et al. Cyclic ADP-ribose is a second messenger in the lipopolysaccharide-stimulated activation of murine N9 microglial cell line. J Neurochem 2006; 99: 165-76.
139. Opitz CA, Wick W, Steinman L, Platten M. Tryptophan degradation in autoimmune diseases. Cell Mol Life Sci 2007; 64: 2542-63.
140. Kaper T, Looger LL, Takanaga H, Platten M, Steinman L, Frommer WB. Nanosensor detection of an immunoregulatory tryptophan influx/kynurenine efflux cycle. PLoS Biol 2007; 5: E257.
141. Penberthy WT. Pharmacological targeting of IDO-mediated tolerance for treating autoimmune disease. Curr Drug Metab 2007; 8: 245-66.
142. Iribarren P, Cui YH, Le Y, Wang JM. The role of dendritic cells in neurodegenerative diseases. Arch Immunol Ther Exp (Warsz) 2002; 50: 187-96.
143. Ifergan I, Kebir H, Bernard M, Wosik K, Dodelet-Devillers A, Cayrol R, et al. The blood-brain barrier induces differentiation of migrating monocytes into Th17-polarizing dendritic cells. Brain 2008; 131: 785-99.
144. Pashenkov M, Teleshova N, Link H. Inflammation in the central nervous system: The role for dendritic cells. Brain Pathol 2003; 13: 23-33.
145. Kauppinen TM, Suh SW, Genain CP, Swanson RA. Poly(ADPribose) polymerase-1 activation in a primate model of multiple sclerosis. J Neurosci Res 2005; 81: 190-8.
146. Sakai K, Nakajima T, Fukuhara N. [A suspected case of alcoholic pellagra encephalopathy with marked response to niacin showing myoclonus and ataxia as chief complaints]. No To Shinkei 2006; 58: 141-4.
147. Piercecchi-Marti MD, Pelissier-Alicot AL, Leonetti G, Terve JP, Cianfarani F, Pellissier JF. Pellagra: A rare disease observed in a victim of mental and physical abuse. Am J Forensic Med Pathol 2004; 25: 342-4.
148. Belladonna ML, Grohmann U, Guidetti P, Volpi C, Bianchi R, Fioretti MC, et al. Kynurenine pathway enzymes in dendritic cells initiate tolerogenesis in the absence of functional IDO. J Immunol 2006; 177: 130-7.
149. Sharma MD, Baban B, Chandler P, Hou DY, Singh N, Yagita H, et al. Plasmacytoid dendritic cells from mouse tumor-draining lymph nodes directly activate mature Tregs via indoleamine 2,3-dioxygenase. J Clin Invest 2007; 117: 2570-82.
150. Malavasi F, Deaglio S, Funaro A, Ferrero E, Horenstein AL, Ortolan E, et al. Evolution and function of the ADP ribosyl cyclase/CD38 gene family in physiology and pathology. Physiol Rev 2008; 88: 841-86.
151. Partida-Sanchez S, Rivero-Nava L, Shi G, Lund FE. CD38: An ecto-enzyme at the crossroads of innate and adaptive immune responses. Adv Exp Med Biol 2007; 590: 171-83.
152. Aksoy P, White TA, Thompson M, Chini EN. Regulation of intracellular levels of NAD: A novel role for CD38. Biochem Biophys Res Commun 2006; 345: 1386-92.
153. Young GS, Choleris E, Lund FE, Kirkland JB. Decreased cADPR and increased NAD+ in the Cd38-/- mouse. Biochem Biophys Res Commun 2006; 346: 188-92.
154. Barbosa MT, Soares SM, Novak CM, Sinclair D, Levine JA, Aksoy P, et al. The enzyme CD38 (a NAD glycohydrolase, EC 3.2.2.5) is necessary for the development of diet-induced obesity. FASEB J 2007; 21: 3629-39.
155. Mallone R, Perin PC. Anti-CD38 autoantibodies in type? diabetes. Diabetes Metab Res Rev 2006; 22: 284-94.
156. Cockayne DA, Muchamuel T, Grimaldi JC, Muller-Steffner H, Randall TD, Lund FE, et al. Mice deficient for the ectonicotinamide adenine dinucleotide glycohydrolase CD38 exhibit altered humoral immune responses. Blood 1998; 92: 1324-33.
157. Rutter GA, Bellomo EA. Ca2+ signalling: A new route to NAADP. Biochem J 2008; 411: E1-3.
158. Vasudevan SR, Galione A, Churchill GC. Sperm express a Ca2+-regulated NAADP synthase. Biochem J 2008; 411: 63-70.
159. Ziegler M. New functions of a long-known molecule. Emerging roles of NAD in cellular signaling. Eur J Biochem 2000; 267: 1550-64.
160. Gul R, Park JH, Kim SY, Jang KY, Chae JK, Ko JK, et al. Inhibition of ADP-ribosyl cyclase attenuates angiotensin II-induced cardiac hypertrophy. Cardiovasc Res 2008.
161. Sims JL, Berger SJ, Berger NA. Poly(ADP-ribose) Polymerase inhibitors preserve nicotinamide adenine dinucleotide and adenosine 5′-triphosphate pools in DNA-damaged cells: Mechanism of stimulation of unscheduled DNA synthesis. Biochemistry 1983; 22: 5188-94.
162. Orciani M, Trubiani O, Guarnieri S, Ferrero E, Di Primio R. CD38 is constitutively expressed in the nucleus of human hematopoietic cells. J Cell Biochem 2008.
163. Jones KS, Alimov AP, Rilo HL, Jandacek RP, Woollett LA, Penberthy WT. A High Throughput Live Transparent Animal Bioassay to Identify Non-toxic Small Molecules or Genes that Regulate Vertebrate Fat Metabolism for Obesity Drug Development. Nutr Metab (Lond) 2008; 5: 23.
164. Iqbal J, Zaidi M. Extracellular NAD+ metabolism modulates osteoclastogenesis. Biochem Biophys Res Commun 2006; 349: 533-9.
165. Roelofs-Haarhuis K, Wu X, Nowak M, Fang M, Artik S, Gleichmann E. Infectious nickel tolerance: A reciprocal interplay of tolerogenic APCs and T suppressor cells that is driven by immunization. J Immunol 2003; 171: 2863-72.
166. Read S, Mauze S, Asseman C, Bean A, Coffman R, Powrie F. CD38+ CD45RB(low) CD4+ T cells: A population of T cells with immune regulatory activities in vitro. Eur J Immunol 1998; 28: 3435-47.
167. McCandless EE, Klein RS. Molecular targets for disrupting leukocyte trafficking during multiple sclerosis. Expert Rev Mol Med 2007; 9: 1-19.
168. Correale J, Villa A. The blood-brain-barrier in multiple sclerosis: functional roles and therapeutic targeting. Autoimmunity 2007; 40: 148-60.
169. Antonelli A, Ferrannini E. CD38 autoimmunity: Recent advances and relevance to human diabetes. J Endocrinol Invest 2004; 27: 695-707.
170. Virag L, Szabo C. The therapeutic potential of poly(ADP-ribose) polymerase inhibitors. Pharmacol Rev 2002; 54: 375-429.
171. Buelow B, Song Y, Scharenberg AM. The poly(ADP-ribose) polymerase PARP-1 is required for oxidative stress-induced TRPM2 activation in lymphocytes. J Biol Chem 2008.
172. Eliasson MJ, Sampei K, Mandir AS, Hurn PD, Traystman RJ, Bao J, et al. Poly(ADP-ribose) polymerase gene disruption renders mice resistant to cerebral ischemia. Nat Med 1997; 3: 1089-95.
173. Endres M, Wang ZQ, Namura S, Waeber C, Moskowitz MA. Ischemic brain
174. Pacher P, Szabo C. Role of the peroxynitrite-poly(ADP-ribose) polymerase pathway in human disease. Am J Pathol 2008; 173: 2-13.
175. Hasko G, Mabley JG, Nemeth ZH, Pacher P, Deitch EA, Szabo C. Poly(ADP-ribose) polymerase is a regulator of chemokine production: relevance for the pathogenesis of shock and inflammation. Mol Med 2002; 8: 283-9.
176. Szabo C, Lim LH, Cuzzocrea S, Getting SJ, Zingarelli B, Flower RJ, et al. Inhibition of poly (ADP-ribose) synthetase attenuates neutrophil recruitment and exerts antiinflammatory effects. J Exp Med 1997; 186: 1041-9.
177. Zingarelli B, Szabo C, Salzman AL. Blockade of Poly(ADP-ribose) synthetase inhibits neutrophil recruitment, oxidant generation, and mucosal injury in murine colitis. Gastroenterology 1999; 116: 335-45
178. Song Y, Buelow B, Perraud AL, Scharenberg AM. Development and validation of a cell-based high-throughput screening assay for TRPM2 channel modulators. J Biomol Screen 2008; 13: 54-61.
179. Okuno A, Fukuwatari T, Shibata K. Urinary excretory ratio of anthranilic acid/kynurenic acid as an index of the tolerable amount of tryptophan. Biosci Biotechnol Biochem 2008; 72: 1667-72.
180. Smith MJ, Garrett RH. A heretofore undisclosed crux of eosinophilia-myalgia syndrome: Compromised histamine degradation. Inflamm Res 2005; 54: 435-50.
181. Silver RM, Heyes MP, Maize JC, Quearry B, Vionnet-Fuasset M, Sternberg EM. Scleroderma, fasciitis, and eosinophilia associated with the ingestion of tryptophan. N Engl J Med 1990; 322: 874-81.
182. Hankes LV, Coenen HH, Rota E, Langen KJ, Herzog H, Wutz W, et al. Effect of Huntington's and Alzheimer's diseases on the transport of nicotinic acid or nicotinamide across the human blood-brain barrier. Adv Exp Med Biol 1991; 294: 675-8.
183. Maiese K, Chong ZZ. Nicotinamide: Necessary nutrient emerges as a novel cytoprotectant for the brain. Trends Pharmacol Sci 2003; 24: 228-32
184. Spector R. Niacin and niacinamide transport in the central nervous system. In vivo studies. J Neurochem 1979; 33: 895-904.
185. Hoffer A. Treatment of arthritis by nicotinic acid and nicotinamide. Can Med Assoc J 1959; 81: 235-8.
186. Hoffer A. Adventures in Psychiatry: The Scientific Memoirs of Dr. Abram Hoffer, KOS Publishing 2005.
187. Yang J, Klaidman LK, Chang ML, Kem S, Sugawara T, Chan P, et al. Nicotinamide therapy protects against both necrosis and apoptosis in a stroke model. Pharmacol Biochem Behav 2002; 73: 901-10.
188. Sheridan C. Genentech raises stakes on PARP inhibitors. Nat Biotechnol 2006; 24: 1179-80.
189. Hoffer A, Osmond H, Callbeck MJ, Kahan I. Treatment of schizophrenia with nicotinic acid and nicotinamide. J Clin Exp Psychopathol 1957; 18: 131-58.
190. Thompson MM, Reed SC, Cockerill GW. Therapeutic approaches to raising plasma HDL-cholesterol levels. Nat Clin Pract Cardiovasc Med 2004; 1: 84-9.
191. Sampietro T, Bigazzi F, Dal Pino B, Puntoni M, Bionda A. HDL: The 'new' target of cardiovascular medicine. Int J Cardiol 2006; 108: 143-54.
192. Vance JE, Campenot RB, Vance DE. The synthesis and transport of lipids for axonal growth and nerve regeneration. Biochim Biophys Acta 2000; 1486: 84-96.
193. Karten B, Hayashi H, Campenot RB, Vance DE, Vance JE. Neuronal models for studying lipid metabolism and transport. Methods 2005; 36: 117-28.
194. Hayashi H, Campenot RB, Vance DE, Vance JE. Apolipoprotein E-containing lipoproteins protect neurons from apoptosis via a signaling pathway involving low-density lipoprotein receptor-related protein-1. J Neurosci 2007; 27: 1933-41.
195. Carter JM, Demizieux L, Campenot RB, Vance DE, Vance JE. Phosphatidylcholine biosynthesis via CTP:pHosphocholine cytidylyltransferase 2 facilitates neurite outgrowth and branching. J Biol Chem 2008; 283: 202-12.
196. Micheli V, Simmonds HA, Sestini S, Ricci C. Importance of nicotinamide as an NAD precursor in the human erythrocyte. Arch Biochem Biophys 1990; 283: 40-5.
197. Henderson LM, Gross CJ. Metabolism of niacin and niacinamide in perfused rat intestine. J Nutr 1979; 109: 654-62.
198. Hara N, Yamada K, Shibata T, Osago H, Hashimoto T, Tsuchiya M. Elevation of cellular NAD levels by nicotinic acid and involvement of nicotinic acid phosphoribosyltransferase in human cells. J Biol Chem 2007; 282: 24574-82.
199. Hernandez M, Wright SD, Cai TQ. Critical role of cholesterol ester transfer protein in nicotinic acid-mediated HDL elevation in mice. Biochem Biophys Res Commun 2007; 355: 1075-80.
200. van der Hoorn JW, de Haan W, Berbee JF, Havekes LM, Jukema JW, Rensen PC, et al. Niacin Increases HDL by Reducing Hepatic Expression and Plasma Levels of Cholesteryl Ester Transfer Protein in APOE*3Leiden.CETP Mice. Arterioscler Thromb Vasc Biol 2008.
201. Rubic T, Trottmann M, Lorenz RL. Stimulation of CD36 and the key effector of reverse cholesterol transport ATP-binding cassette A1 in monocytoid cells by niacin. Biochem Pharmacol 2004; 67: 411-9.
202. Zhao SP, Yang J, Li J, Dong SZ, Wu ZH. Effect of niacin on LXRalpha and PPARgamma expression and HDL-induced cholesterol efflux in adipocytes of hypercholesterolemic rabbits. Int J Cardiol 2008; 124: 172-8.
203. Kamanna VS, Kashyap ML. Mechanism of action of niacin. Am J Cardiol 2008; 101: 20B-26B.
204. Santos-Gallego CG, Ibanez B, Badimon JJ. HDL-cholesterol: Is it really good? Differences between apoA-I and HDL. Biochem Pharmacol 2008; 76: 443-52.
205. Tall AR, Yvan-Charvet L, Terasaka N, Pagler T, Wang N. HDL, ABC transporters, and cholesterol efflux: Implications for the treatment of atherosclerosis. Cell Metab 2008; 7: 365-75.
206. Joy T, Hegele RA. Is raising HDL a futile strategy for atheroprotection? Nat Rev Drug Discov 2008; 7: 143-55.
207. Tunaru S, Kero J, Schaub A, Wufka C, Blaukat A, Pfeffer K, et al. PUMA-G and HM74 are receptors for nicotinic acid and mediate its anti-lipolytic effect. Nat Med 2003; 9: 352-5.
208. Knowles HJ, te Poele RH, Workman P, Harris AL. Niacin induces PPARgamma expression and transcriptional activation in macrophages via HM74 and HM74a-mediated induction of prostaglandin synthesis pathways. Biochem Pharmacol 2006; 71: 646-56.
209. Storer PD, Xu J, Chavis JA, Drew PD. Cyclopentenone prostaglandins PGA2 and 15-deoxy-delta12,14 PGJ2 suppress activation of murine microglia and astrocytes: Implications for multiple sclerosis. J Neurosci Res 2005; 80: 66-74.
210. Diab A, Deng C, Smith JD, Hussain RZ, Phanavanh B, Lovett-Racke AE, et al. Peroxisome proliferator-activated receptor-gamma agonist 15-deoxy-Delta(12,14)-prostaglandin J(2) ameliorates experimental autoimmune encephalomyelitis. J Immunol 2002; 168: 2508-15.
211. Diab A, Hussain RZ, Lovett-Racke AE, Chavis JA, Drew PD, Racke MK. Ligands for the peroxisome proliferator-activated receptor-gamma and the retinoid X receptor exert additive antiinflammatory effects on experimental autoimmune encephalomyelitis. J Neuroimmunol 2004; 148: 116-26.
212. Kaplan JM, Cook JA, Hake PW, O'Connor M, Burroughs TJ, Zingarelli B. 15-Deoxy-delta(12,14)-prostaglandin J(2) (15D-PGJ(2)), a peroxisome proliferator activated receptor gamma ligand, reduces tissue leukosequestration and mortality in endotoxic shock. Shock 2005; 24: 59-65.
213. Gille A, Bodor ET, Ahmed K, Offermanns S. Nicotinic acid: pharmacological effects and mechanisms of action. Annu Rev Pharmacol Toxicol 2008; 48: 79-106.
214. Taggart AK, Kero J, Gan X, Cai TQ, Cheng K, Ippolito M, et al. (D)-{beta}-Hydroxybutyrate Inhibits Adipocyte Lipolysis via the Nicotinic Acid Receptor PUMA-G. J Biol Chem 2005; 280: 26649-52.
215. Braun D, Longman RS, Albert ML. A two-step induction of indoleamine 2,3 dioxygenase (IDO) activity during dendritic-cell maturation. Blood 2005; 106: 2375-81.
216. Basu TK, Mann S. Vitamin B-6 normalizes the altered sulfur amino acid status of rats fed diets containing pharmacological levels of niacin without reducing niacin's hypolipidemic effects. J Nutr 1997; 127: 117-21.
217. Garg R, Malinow M, Pettinger M, Upson B, Hunninghake D. Niacin treatment increases plasma homocyst(e)ine levels. Am Heart J 1999; 138: 1082-7.
218. Basu TK, Makhani N, Sedgwick G. Niacin (nicotinic acid) in non-physiological doses causes hyperhomocysteineaemia in Sprague-Dawley rats. Br J Nutr 2002; 87: 115-9.
219. Reynolds EH. Multiple sclerosis and vitamin B12 metabolism. J Neuroimmunol 1992; 40: 225-30.
220. Dror DK, Allen LH. Effect of vitamin B12 deficiency on neurodevelopment in infants: Current knowledge and possible mechanisms. Nutr Rev 2008; 66: 250-5.
221. Aoyagi S, Archer TK. Nicotinamide uncouples hormone-dependent chromatin remodeling from transcription complex assembly. Mol Cell Biol 2008; 28: 30-9.
222. Chong ZZ, Lin SH, Li F, Maiese K. The sirtuin inhibitor nicotinamide enhances neuronal cell survival during acute anoxic injury through AKT, BAD, PARP, and mitochondrial associated "antiapoptotic" pathways. Curr Neurovasc Res 2005; 2: 271-85.
223. Bieganowski P, Brenner C. Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a Preiss-Handler independent route to NAD+ in fungi and humans. Cell 2004; 117: 495-502.
224. Luk T, Malam Z, Marshall JC. Pre-B cell colony-enhancing factor (PBEF)/ visfatin: A novel mediator of innate immunity. J Leukoc Biol 2008; 83: 804-16.
225. Revollo JR, Korner A, Mills KF, Satoh A, Wang T, Garten A, et al. Nampt/PBEF/Visfatin regulates insulin secretion in beta cells as a systemic NAD biosynthetic enzyme. Cell Metab 2007; 6: 363-75.
226. Marks PA. Discovery and development of SAHA as an anticancer agent. Oncogene 2007; 26: 1351-6.
227. Reddy P, Sun Y, Toubai T, Duran-Struuck R, Clouthier SG, Weisiger E, et al. Histone deacetylase inhibition modulates indoleamine 2,3-dioxygenase-dependent DC functions and regulates experimental graft-versus-host disease in mice. J Clin Invest 2008; 118: 2562-73.
228. Kyrylenko S, Kyrylenko O, Suuronen T, Salminen A. Differential regulation of the Sir2 histone deacetylase gene family by inhibitors of class I and II histone deacetylases. Cell Mol Life Sci 2003; 60: 1990-7.
229. Singh NP, Hegde V, Hofseth LJ, Nagarkatti M, Nagarkatti P. Resveratrol (trans-3,5,4′'-trihydroxystilbene) Ameliorates Experimental Allergic Encephalomyelitis (EAE) Primarily via Induction of Apoptosis in T cells Involving Activation of AhR and ER. Mol Pharmacol 2007.
230. Schwer B, Verdin E. Conserved metabolic regulatory functions of sirtuins. Cell Metab 2008; 7: 104-12.
231. Michishita E, Park JY, Burneskis JM, Barrett JC, Horikawa I. Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins. Mol Biol Cell 2005; 16: 4623-35.
232. Sundaresan NR, Samant SA, Pillai VB, Rajamohan SB, Gupta MP. SIRT3 is a stress responsive deacetylase in cardiomyocytes that protects cells from stress-mediated cell death by deacetylation of Ku-70. Mol Cell Biol 2008.
233. Tanno M, Sakamoto J, Miura T, Shimamoto K, Horio Y. Nucleocytoplasmic shuttling of the NAD+-dependent histone deacetylase SIRT1. J Biol Chem 2007; 282: 6823-32.
234. Nakamura Y, Ogura M, Tanaka D, Inagaki N. Localization of mouse mitochondrial SIRT proteins: Shift of SIRT3 to nucleus by co-expression with SIRT5. Biochem Biophys Res Commun 2008; 366: 174-9.
235. Scher MB, Vaquero A, Reinberg D. SIRT3 is a nuclear NAD+-dependent histone deacetylase that translocates to the mitochondria upon cellular stress. Genes Dev 2007; 21: 920-8.
236. Cooper HM, Spelbrink JN. The human SIRT3 protein deacetylase is exclusively mitochondrial. Biochem J 2008; 411: 279-85.
237. Lin SJ, Defossez PA, Guarente L. Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae. Science 2000; 289: 2126-8.
238. Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 2003; 425: 191-6.
239. Sequeira J, Boily G, Bazinet S, Saliba S, He X, Jardine K, et al. SIRT1-null mice develop an autoimmune-like condition. Exp Cell Res 2008.
240. Baur JA, Sinclair DA. Therapeutic potential of resveratrol: The in vivo evidence. Nat Rev Drug Discov 2006; 5: 493-506.
241. Sun AY, Simonyi A, Sun GY. The "French Paradox" and beyond: neuroprotective effects of polyphenols. Free Radic Biol Med 2002; 32: 314-8.
242. Liu BL, Zhang X, Zhang W, Zhen HN. New enlightenment of French Paradox: resveratrol's potential for cancer chemoprevention and anti-cancer therapy. Cancer Biol Ther 2007; 6: 1833-6.
243. Aggarwal BB, Shishodia S. Resveratrol in health and disease, CRC Taylor & Francis: Boca Raton 2006.
244. Dasgupta B, Milbrandt J. Resveratrol stimulates AMP kinase activity in neurons. Proc Natl Acad Sci USA 2007; 104: 7217-22.
245. Werner HB, Kuhlmann K, Shen S, Uecker M, Schardt A, Dimova K, et al. Proteolipid protein is required for transport of sirtuin 2 into CNS myelin. J Neurosci 2007; 27: 7717-30.
246. Southwood CM, Peppi M, Dryden S, Tainsky MA, Gow A. Microtubule deacetylases, SIRT2 and HDAC6, in the nervous system. Neurochem Res 2007; 32: 187-95.
247. Vaquero A, Sternglanz R, Reinberg D. NAD+-dependent deacetylation of H4 lysine 16 by class III HDACs. Oncogene 2007; 26: 5505-20.
248. Zhang F, Sun C, Wu J, He C, Ge X, Huang W, et al. Combretastatin A-4 activates AMP-activated protein kinase and improves glucose metabolism in db/db mice. Pharmacol Res 2008; 57: 318-23.
249. Tian WX. Inhibition of fatty acid synthase by polyphenols. Curr Med Chem 2006; 13: 967-77.
250. Prozorovski T, Schulze-Topphoff U, Glumm R, Baumgart J, Schroter F, Ninnemann O, et al. SIRT1 contributes critically to the redox- dependent fate of neural progenitors. Nat Cell Biol 2008; 10: 385-94
251. Libert S, Cohen D, Guarente L. Neurogenesis directed by SIRT1. Nat Cell Biol 2008; 10: 373-4.
252. Ganji SH, Qin S, Zhang L, Kamanna VS, Kashyap ML. Niacin inhibits vascular oxidative stress, redox-sensitive genes, and monocyte adhesion to human aortic endothelial cells. Atherosclerosis 2008.
253. Gan L, Mucke L. Paths of convergence: Sirtuins in aging and neurodegeneration. Neuron 2008; 58: 10-4.
254. Ruggieri M, Pica C, Lia A, Zimatore GB, Modesto M, Di Liddo E, et al. Combination treatment of Glatiramer Acetate and Minocycline affects phenotype expression of blood monocyte-derived dendritic cells in Multiple Sclerosis patients. J Neuroimmunol 2008.
255. Luccarini I, Ballerini C, Biagioli T, Biamonte F, Bellucci A, Rosi MC, et al. Combined treatment with atorvastatin and minocycline suppresses severity of EAE. Exp Neurol 2008; 211: 214-26.
256. Herrmann I, Kellert M, Spreer A, Gerber J, Eiffert H, Prinz M, et al. Minocycline delays but does not attenuate the course of experimental autoimmune encephalomyelitis in Streptococcus pneumoniae-infected mice. J Antimicrob Chemother 2007; 59: 74-9.
257. Giuliani F, Fu SA, Metz LM, Yong VW. Effective combination of minocycline and interferon-beta in a model of multiple sclerosis. J Neuroimmunol 2005; 165: 83-91.
258. Scott GS, Kean RB, Mikheeva T, Fabis MJ, Mabley JG, Szabo C, et al. The therapeutic effects of PJ34 N-(6-oxo-5,6-dihydrophen-anthridin-2-yl)-N,N-dimethylacetamide.HCl], a selective inhibitor of poly(ADP-ribose) polymerase, in experimental allergic encephalomyelitis are associated with immunomodulation. J Pharmacol Exp Ther 2004; 310: 1053-61.
259. Brundula V, Rewcastle NB, Metz LM, Bernard CC, Yong VW. Targeting leukocyte MMPs and transmigration: Minocycline as a potential therapy for multiple sclerosis. Brain 2002; 125: 1297-308.
260. Scott GS, Hake P, Kean RB, Virag L, Szabo C, Hooper DC. Role of poly(ADP-ribose) synthetase activation in the development of experimental allergic encephalomyelitis. J Neuroimmunol 2001; 117: 78-86.
261. Kauppinen TM. Multiple roles for poly(ADP-ribose)polymerase-1 in neurological disease. Neurochem Int 2007; 50: 954-8.
262. Mirshafiey A, Mohsenzadegan M. Antioxidant Therapy in Multiple Sclerosis. Immunopharmacol Immunotoxicol 2008: 1-34.
263. van Horssen J, Schreibelt G, Bo L, Montagne L, Drukarch B, van Muiswinkel FL, et al. NAD(P)H:qUinone oxidoreductase 1 expression in multiple sclerosis lesions. Free Radic Biol Med 2006; 41: 311-7.
264. Schraufstatter IU, Hinshaw DB, Hyslop PA, Spragg RG, Cochrane CG. Oxidant injury of cells. DNA strand-breaks activate polyadenosine diphosphate-ribose polymerase and lead to depletion of nicotinamide adenine dinucleotide. J Clin Invest 1986; 77: 1312-20.
265. Bedard K, Krause KH. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 2007; 87: 245-313.
266. Lefkowitz DL, Lefkowitz SS. Microglia and myeloperoxidase: A deadly partnership in neurodegenerative disease. Free Radic Biol Med 2008; 45: 726-31.
267. Liu Y, Hao W, Letiembre M, Walter S, Kulanga M, Neumann H, et al. Suppression of microglial inflammatory activity by myelin phagocytosis: role of p47-PHOX-mediated generation of reactive oxygen species. J Neurosci 2006; 26: 12904-13.
268. Benavente CA, Jacobson EL. Niacin restriction upregulates NADPH oxidase and reactive oxygen species (ROS) in human keratinocytes. Free Radic Biol Med 2008; 44: 527-37.
269. Stirling DP, Koochesfahani KM, Steeves JD, Tetzlaff W. Minocycline as a neuroprotective agent. Neuroscientist 2005; 11: 308-22.
270. Rasouri S, Lagouge M, Auwerx J. [SIRT1/PGC-1: A neuroprotective axis?]. Med Sci (Paris) 2007; 23: 840-4.
271. Lawson TM, Amos N, Bulgen D, Williams BD. Minocycline-induced lupus: clinical features and response to rechallenge. Rheumatology (Oxford) 2001; 40: 329-35.
272. Hess EV. Environmental chemicals and autoimmune disease: Cause and effect. Toxicology 2002; 181-182: 65-70.
273. Mongey AB, Hess EV. Drug insight: Autoimmune effects of medications-what's new? Nat Clin Pract Rheumatol 2008; 4: 136-44.
274. Margolis DJ, Hoffstad O, Bilker W. Association or lack of association between tetracycline class antibiotics used for acne vulgaris and lupus erythematosus. Br J Dermatol 2007; 157: 540-6.
275. Morimoto N, Shimazawa M, Yamashima T, Nagai H, Hara H. Minocycline inhibits oxidative stress and decreases in vitro and in vivo ischemic neuronal damage. Brain Res 2005; 1044: 8-15.
276. Yrjanheikki J, Keinanen R, Pellikka M, Hokfelt T, Koistinaho J. Tetracyclines inhibit microglial activation and are neuroprotective in global brain ischemia. Proc Natl Acad Sci USA 1998; 95: 15769-74.
277. Rubin RL. Drug-induced lupus. Toxicology 2005; 209: 135-47.
278. Drazen DL, Bilu D, Edwards N, Nelson RJ. Disruption of poly (ADP-ribose) polymerase (PARP) protects against stress-evoked immunocompromise. Mol Med 2001; 7: 761-6.
279. Aldinucci A, Gerlini G, Fossati S, Cipriani G, Ballerini C, Biagioli T, et al. A key role for poly(ADP-ribose) polymerase-1 activity during human dendritic cell maturation. J Immunol 2007; 179: 305-12.
280. Grader-Beck T, Casciola-Rosen L, Lang TJ, Puliaev R, Rosen A, Via CS. Apoptotic splenocytes drive the autoimmune response to poly(ADP-ribose) polymerase 1 in a murine model of lupus. J Immunol 2007; 178: 95-102.
281. Olabisi OA, Soto-Nieves N, Nieves E, Yang TT, Yang X, Yu RY, et al. Regulation of transcription factor NFAT by ADP-ribosylation. Mol Cell Biol 2008; 28: 2860-71.
282. Saenz L, Lozano JJ, Valdor R, Baroja-Mazo A, Ramirez P, Parrilla P, et al. Transcriptional regulation by poly(ADP-ribose) polymerase-1 during T cell activation. BMC Genomics 2008; 9: 171.
283. Schraufstatter IU, Hyslop PA, Jackson J, Cochrane CC. Oxidant injury of cells. Int J Tissue React 1987; 9: 317-24.
284. Yoshida M, Macklin WB. Oligodendrocyte development and myelination in GFP-transgenic zebrafish. J Neurosci Res 2005; 81: 1-8.
285. Pogoda HM, Sternheim N, Lyons DA, Diamond B, Hawkins TA, Woods IG, et al. A genetic screen identifies genes essential for development of myelinated axons in zebrafish. Dev Biol 2006; 298: 118-31.
286. Panula P, Sallinen V, Sundvik Y, Kolehmainen J, Torkko V, Tiittula A, et al. Modulatory Neurotransmitter Systems and Behavior: Towards Zebrafish Models of Neurodegenerative Diseases Zebrafish 2007; 3: 235-247.
287. Chan J, Ban EJ, Chun KH, Wang S, McQualter J, Bernard C, et al. Methylprednisolone induces reversible clinical and pathological remission and loss of lymphocyte reactivity to myelin oligodendrocyte glycoprotein in experimental autoimmune encephalomyelitis. Autoimmunity 2008; 41: 405-13.
288. Tsunoda I, Fujinami RS. Inside-Out versus Outside-In models for virus induced demyelination: Axonal damage triggering demyelination. Springer Semin Immunopathol 2002; 24: 105-25.
289. Konno H, Yamamoto T, Suzuki H, Yamamoto H, Iwasaki Y, Ohara Y, et al. Targeting of adoptively transferred experimental allergic encephalitis lesion at the sites of Wallerian degeneration. Acta Neuropathol 1990; 80: 521-6.
290. Tsunoda I, Tanaka T, Saijoh Y, Fujinami RS. Targeting inflammatory demyelinating lesions to sites of Wallerian degeneration. Am J Pathol 2007; 171: 1563-75.
291. Barres BA, Raff MC. Axonal control of oligodendrocyte development. J Cell Biol 1999; 147: 1123-8.
292. Beattie CE, Melancon E, Eisen JS. Mutations in the stumpy gene reveal intermediate targets for zebrafish motor axons. Development 2000; 127: 2653-62.
293. Crowe MJ, Bresnahan JC, Shuman SL, Masters JN, Beattie MS. Apoptosis and delayed degeneration after spinal cord injury in rats and monkeys. Nat Med 1997; 3: 73-6.
294. Lassmann H, Ammerer HP, Kulnig W. Ultrastructural sequence of myelin degradation. I. Wallerian degeneration in the rat optic nerve. Acta Neuropathol 1978; 44: 91-102.
295. McPhilemy K, Mitchell LS, Griffiths IR, Morrison S, Deary AW, Sommer I, et al. Effect of optic nerve transection upon myelin protein gene expression by oligodendrocytes: Evidence for axonal influences on gene expression. J Neurocytol 1990; 19: 494-503.
296. Jiang H, Duchala CS, Awatramani R, Shumas S, Carlock L, Kamholz J, et al. Proteolipid protein mRNA stability is regulated by axonal contact in the rodent peripheral nervous system. J Neurobiol 2000; 44: 7-19
297. Popko B. Myelin: Not just a conduit for conduction. Nat Genet 2003; 33: 327-8.
298. Lappe-Siefke C, Goebbels S, Gravel M, Nicksch E, Lee J, Braun PE, et al. Disruption of Cnp1 uncouples oligodendroglial functions in axonal support and myelination. Nat Genet 2003; 33: 366-74.
299. Tang BL, Chua CE. SIRT2, tubulin deacetylation, and oligodendroglia differentiation. Cell Motil Cytoskeleton 2008; 65: 179-82.
300. Konno H, Yamamoto T, Iwasaki Y, Suzuki H, Saito T, Terunuma H. Wallerian degeneration induces Ia-antigen expression in the rat brain. J Neuroimmunol 1989; 25: 151-9.
301. Block ML, Zecca L, Hong JS. Microglia-mediated neurotoxicity: Uncovering the molecular mechanisms. Nat Rev Neurosci 2007; 8: 57-69.
302. Miller RH, Bai L. Cellular approaches for stimulating CNS remyelination. Regen Med 2007; 2: 817-29.
303. Einstein O, Ben-Hur T. The changing face of neural stem cell therapy in neurologic diseases. Arch Neurol 2008; 65: 452-6.
304. Pluchino S, Quattrini A, Brambilla E, Gritti A, Salani G, Dina G, et al. Injection of adult neurospheres induces recovery in a chronic model of multiple sclerosis. Nature 2003; 422: 688-94.
305. Zappia E, Casazza S, Pedemonte E, Benvenuto F, Bonanni I, Gerdoni E, et al. Mesenchymal stem cells ameliorate experimental autoimmune encephalomyelitis inducing T-cell anergy. Blood 2005; 106: 1755-61.
306. Einstein O, Fainstein N, Vaknin I, Mizrachi-Kol R, Reihartz E, Grigoriadis N, et al. Neural precursors attenuate autoimmune encephalomyelitis by peripheral immunosuppression. Ann Neurol 2007; 61: 209-18.
307. Gerdoni E, Gallo B, Casazza S, Musio S, Bonanni I, Pedemonte E, et al. Mesenchymal stem cells effectively modulate pathogenic immune response in experimental autoimmune encephalomyelitis. Ann Neurol 2007; 61: 219-27.
308. Pluchino S, Zanotti L, Rossi B, Brambilla E, Ottoboni L, Salani G, et al. Neurosphere-derived multipotent precursors promote neuroprotection by an immunomodulatory mechanism. Nature 2005; 436: 266-71.
309. Partida-Sanchez S, Iribarren P, Moreno-Garcia ME, Gao JL, Murphy PM, Oppenheimer N, et al. Chemotaxis and calcium responses of phagocytes to formyl peptide receptor ligands is differentially regulated by cyclic ADP ribose. J Immunol 2004; 172: 1896-906.
310. Han MK, Song EK, Guo Y, Ou X, Mantel C, Broxmeyer HE. SIRT1 regulates apoptosis and Nanog expression in mouse embryonic stem cells by controlling p53 subcellular localization. Cell Stem Cell 2008; 2: 241-51.
311. Mantel CR, Wang RH, Deng C, Broxmeyer HE. SIRT1, notch and stem cell "age asymmetry". Cell Cycle 2008; 7: 2821-5.
312. Hisahara S, Chiba S, Matsumoto H, Tanno M, Yagi H, Shimohama S, et al. Histone deacetylase SIRT1 modulates neuronal differentiation by its nuclear translocation. Proc Natl Acad Sci USA 2008.
313. Vaziri H, Dessain SK, Ng Eaton E, Imai SI, Frye RA, Pandita TK, et al. hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase. Cell 2001; 107: 149-59.
314. Benyo Z, Gille A, Kero J, Csiky M, Suchankova MC, Nusing RM, et al. GPR109A (PUMA-G/HM74A) mediates nicotinic acid-induced flushing. J Clin Invest 2005; 115: 3634-40.
315. North TE, Goessling W, Walkley CR, Lengerke C, Kopani KR, Lord AM, et al. Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis. Nature 2007; 447: 1007-11.
316. Broxmeyer HE. Mechanism unknown: Prostaglandin E2 may improve HSC therapies. Cell Stem Cell 2007; 1: 135-6.
317. von Bergwelt-Baildon MS, Popov A, Saric T, Chemnitz J, Classen S, Stoffel MS, et al. CD25 and indoleamine 2,3-dioxygenase are up-regulated by prostaglandin E2 and expressed by tumor-associated dendritic cells in vivo: Additional mechanisms of T-cell inhibition. Blood 2006; 108: 228-37.
318. Zheng X, Koropatnick J, Li M, Zhang X, Ling F, Ren X, et al. Reinstalling antitumor immunity by inhibiting tumor-derived immunosuppressive molecule IDO through RNA interference. J Immunol 2006; 177: 5639-46.
319. Muller AJ, DuHadaway JB, Donover PS, Sutanto-Ward E, Prendergast GC. Inhibition of indoleamine 2,3-dioxygenase, an immunoregulatory target of the cancer suppression gene Bin1, potentiates cancer chemotherapy. Nat Med 2005; 11: 312-9.
320. Uyttenhove C, Pilotte L, Theate I, Stroobant V, Colau D, Parmentier N, et al. Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat Med 2003; 9: 1269-74.
321. Williams AC, Ramsden DB. Pellagra: A clue as to why energy failure causes diseases? Med Hypotheses 2007; 69: 618-28.
322. Lanska DJ. Stages in the recognition of epidemic pellagra in the United States: 1865-1960. Neurology 1996; 47: 829-34.
323. Darvay A, Basarab T, McGregor JM, Russell-Jones R. Isoniazid induced pellagra despite pyridoxine supplementation. Clin Exp Dermatol 1999; 24: 167-9.
324. Jorgensen J. Pellagra probably due to pyrazinamide: Development during combined chemotherapy of tuberculosis. Int J Dermatol 1983; 22: 44-5
325. Stevens HP, Ostlere LS, Begent RH, Dooley JS, Rustin MH. Pellagra secondary to 5-fluorouracil. Br J Dermatol 1993; 128: 578-80.
326. Dreizen S, McCredie KB, Keating MJ, Andersson BS. Nutritional deficiencies in patients receiving cancer chemotherapy. Postgrad Med 1990; 87: 163-7, 170.
327. Monteiro JP, da Cunha DF, Filho DC, Silva-Vergara ML, dos Santos VM, da Costa JC, Jr., et al. Niacin metabolite excretion in alcoholic pellagra and AIDS patients with and without diarrhea. Nutrition 2004; 20: 778-82.
328. Jacobson EL. Niacin deficiency and cancer in women. J Am Coll Nutr 1993; 12: 412-6.
329. Leigh D. Pellagra and the nutritional neuropathies: A neuropathological review. J Ment Sci 1952; 98: 130-42.
330. Hyyppa MT, Jolma T, Riekkinen P, Rinne UK. Effects of L-tryptophan treatment on central indoleamine metabolism and shortlasting neurologic disturbances in multiple sclerosis. J Neural Transm 1975; 37: 297-304.
331. Harrer G, Fischbach R. [Effect of specific amino acids on the hotbath- test in multiple sclerosis patients]. J Neural Transm 1973; 34: 205-14.
332. Platten M, Ho PP, Youssef S, Fontoura P, Garren H, Hur EM, et al. Treatment of autoimmune neuroinflammation with a synthetic tryptophan metabolite. Science 2005; 310: 850-5.
333. Asimov I. Asimov's Giude to Science, Basic Books Inc., Publishers: New York 1972.
334. Kirkland J. Handbook of vitamins, Taylor & Francis: Boca Raton 2007.
335. Elvehjem CA, Madden RJ, Strong FM, Woolley DW. Relation of nicotinic acid and nicotinic acid amide to canine black tongue. J. Am. Chem. Soc. 1937; 59: 1767.
336. Pollan M. In Defense of Food: An Eater's Manifesto, Penguin Press 2008.
337. Cleave TL. The saccharine disease: Conditions caused by the taking of refined carbohydrates, such as sugar and white flour, J. Wright: Bristol 1974.
338. Horvath EM, Benko R, Gero D, Kiss L, Szabo C. Treatment with insulin inhibits poly(ADP-ribose)polymerase activation in a rat model of endotoxemia. Life Sci 2008; 82: 205-9.
339. Ihnat MA, Thorpe JE, Kamat CD, Szabo C, Green DE, Warnke LA, et al. Reactive oxygen species mediate a cellular 'memory' of high glucose stress signalling. Diabetologia 2007; 50: 1523-31.
340. Willcock HG, Hopkins FG. Nutrition classics from The Journal of Physiology 35:88-102, 1906-1907.
341. The importance of individual amino-acids in metabolism. Observations on the effect of adding tryptophane to a dietary in which zein is the sole nitrogenous constituent. By Edith G. Willcock and F. Gowland Hopkins. Nutr Rev 1975; 33: 15-7.
342. Fernstrom JD, Wurtman RJ. Effect of chronic corn consumption on serotonin content of rat brain. Nat New Biol 1971; 234: 62-4.
343. Pollan M. The omnivore's dilemma: A natural history of four meals, Penguin Press: New York 2006.
344. Bertram L, Tanzi RE. The genetic epidemiology of neurodegenerative disease. J Clin Invest 2005; 115: 1449-57.
345. Piccio L, Buonsanti C, Mariani M, Cella M, Gilfillan S, Cross AH, et al. Blockade of TREM-2 exacerbates experimental autoimmune encephalomyelitis. Eur J Immunol 2007; 37: 1290-301.
346. Orabona C, Puccetti P, Vacca C, Bicciato S, Luchini A, Fallarino F, et al. Toward the identification of a tolerogenic signature in IDO-competent dendritic cells. Blood 2006; 107: 2846-54.