Mitochondrial sirtuins - a new therapeutic target for repair and protection in multiple sclerosis

European Journal of Neuroscience

Volumn 35, Issue 12, 2012, Pages 1887-1893

  Rice, C M ^a   Sun, M ^a   Kemp, K ^a   Gray, E ^a   Wilkins, A ^a   Scolding, N J ^a  

^a UNIVERSITY OF BRISTOL   (United Kingdom)

Author keywords

Mitochondrial sirtuins; Multiple sclerosis; Neurodegeneration; Neuroprotection; Repair

Indexed keywords

CYCLOPHILIN D; GLUTAMATE DEHYDROGENASE; INDOLEAMINE 2,3 DIOXYGENASE; MANGANESE SUPEROXIDE DISMUTASE; MITOCHONDRIAL DNA; NICOTINAMIDE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR; PROTEIN C JUN; REACTIVE NITROGEN SPECIES; REACTIVE OXYGEN METABOLITE; RESVERATROL; SIRTUIN; SIRTUIN 1; SIRTUIN 2; SIRTUIN 3; SIRTUIN 4; SIRTUIN 5; SIRTUIN 6; SIRTUIN 7;

ALLERGIC ENCEPHALOMYELITIS; ARTICLE; CALORIC RESTRICTION; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DRUG TARGETING; EXCITOTOXICITY; HUMAN; HUNTINGTON CHOREA; MULTIPLE SCLEROSIS; NEUROPROTECTION; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION;

ADULT; HUMANS; MITOCHONDRIA; MOLECULAR TARGETED THERAPY; MULTIPLE SCLEROSIS; OXIDATIVE STRESS; SIRTUINS;

EID: 84862684427     PISSN: 0953816X     EISSN: 14609568     Source Type: Journal    
DOI: 10.1111/j.1460-9568.2012.08150.x     Document Type: Article

References (127)

1. Ahn, B.H., Kim, H.S., Song, S., Lee, I.H., Liu, J., Vassilopoulos, A., Deng, C.X. & Finkel, T. (2008) A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis. Proc. Natl Acad. Sci. U.S.A., 105, 14447-14452.
2. Ahuja, N., Schwer, B., Carobbio, S., Waltregny, D., North, B.J., Castronovo, V., Maechler, P. & Verdin, E. (2007) Regulation of insulin secretion by SIRT4, a mitochondrial ADP-ribosyltransferase. J. Biol. Chem., 282, 33583-33592.
3. Albani, D., Polito, L., Signorini, A. & Forloni, G. (2010) Neuroprotective properties of resveratrol in different neurodegenerative disorders. BioFactors, 36, 370-376.
4. Aljada, A., Dong, L. & Mousa, S.A. (2010) Sirtuin-targeting drugs: mechanisms of action and potential therapeutic applications. Curr. Opin. Investig. Drugs, 11, 1158-1168.
5. Allison, S.J. & Milner, J. (2007) SIRT3 is pro-apoptotic and participates in distinct basal apoptotic pathways. Cell Cycle, 6, 2669-2677.
6. Balcerczyk, A. & Pirola, L. (2010) Therapeutic potential of activators and inhibitors of sirtuins. BioFactors, 36, 383-393.
7. Ban, M., Elson, J., Walton, A., Turnbull, D., Compston, A., Chinnery, P. & Sawcer, S. (2008) Investigation of the role of mitochondrial DNA in multiple sclerosis susceptibility. PLoS One, 3, e2891.
8. Bell, E.L., Emerling, B.M., Ricoult, S.J. & Guarente, L. (2011) SirT3 suppresses hypoxia inducible factor 1alpha and tumor growth by inhibiting mitochondrial ROS production. Oncogene, 30, 2986-2996.
9. Blokhin, A., Vyshkina, T., Komoly, S. & Kalman, B. (2008) Variations in mitochondrial DNA copy numbers in MS brains. J. Mol. Neurosci., 35, 283-287.
10. Bonda, D.J., Lee, H.G., Camins, A., Pallas, M., Casadesus, G., Smith, M.A. & Zhu, X. (2011) The sirtuin pathway in ageing and Alzheimer disease: mechanistic and therapeutic considerations. Lancet Neurol., 10, 275-279.
11. Calvanese, V. & Fraga, M.F. (2011) SirT1 brings stemness closer to cancer and aging. Aging (Albany NY), 3, 162-167.
12. Calvanese, V., Lara, E., Suarez-Alvarez, B., Abu Dawud, R., Vazquez-Chantada, M., Martinez-Chantar, M.L., Embade, N., Lopez-Nieva, P., Horrillo, A., Hmadcha, A., Soria, B., Piazzolla, D., Herranz, D., Serrano, M., Mato, J.M., Andrews, P.W., Lopez-Larrea, C., Esteller, M. & Fraga, M.F. (2010) Sirtuin 1 regulation of developmental genes during differentiation of stem cells. Proc. Natl Acad. Sci. U.S.A., 107, 13736-13741.
13. Campbell, G.R., Ziabreva, I., Reeve, A.K., Krishnan, K.J., Reynolds, R., Howell, O., Lassmann, H., Turnbull, D.M. & Mahad, D.J. (2011) Mitochondrial DNA deletions and neurodegeneration in multiple sclerosis. Ann. Neurol., 69, 481-492.
14. Campbell, G.R. & Mahad, D.J. (2012) Mitochondrial changes associated with demyelination: consequences for axonal integrity. Mitochondrion, 12, 173-179.
15. Carafa, V., Nebbioso, A. & Altucci, L. (2012) Sirtuins and disease: the road ahead. Front. Pharmacol., 3, 4.
16. Caton, P.W., Holness, M.J., Bishop-Bailey, D. & Sugden, M.C. (2011) PPARalpha-LXR as a novel metabolostatic signaling axis in skeletal muscle which acts to optimize substrate selection in response to nutrient status. Biochem J., 437, 521-530.
17. Chen, J., Zhou, Y., Mueller-Steiner, S., Chen, L.F., Kwon, H., Yi, S., Mucke, L. & Gan, L. (2005) SIRT1 protects against microglia-dependent amyloid-beta toxicity through inhibiting NF-kappaB signaling. J. Biol. Chem., 280, 40364-40374.
18. Chen, D., Bruno, J., Easlon, E., Lin, S.J., Cheng, H.L., Alt, F.W. & Guarente, L. (2008) Tissue-specific regulation of SIRT1 by calorie restriction. Genes Dev., 22, 1753-1757.
19. Chen, Y., Zhang, J., Lin, Y., Lei, Q., Guan, K.L., Zhao, S. & Xiong, Y. (2011) Tumour suppressor SIRT3 deacetylates and activates manganese superoxide dismutase to scavenge ROS. EMBO Rep., 12, 534-541.
20. Cimen, H., Han, M.J., Yang, Y., Tong, Q., Koc, H. & Koc, E.C. (2010) Regulation of succinate dehydrogenase activity by SIRT3 in mammalian mitochondria. Biochemistry, 49, 304-311.
21. Cohen, H.Y., Miller, C., Bitterman, K.J., Wall, N.R., Hekking, B., Kessler, B., Howitz, K.T., Gorospe, M., de Cabo, R. & Sinclair, D.A. (2004) Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science, 305, 390-392.
22. Dali-Youcef, N., Lagouge, M., Froelich, S., Koehl, C., Schoonjans, K. & Auwerx, J. (2007) Sirtuins: the 'magnificent seven', function, metabolism and longevity. Ann. Med., 39, 335-345.
23. Donmez, G. & Guarente, L. (2010) Aging and disease: connections to sirtuins. Aging Cell, 9, 285-290.
24. Dutta, R. & Trapp, B.D. (2007) Pathogenesis of axonal and neuronal damage in multiple sclerosis. Neurology, 68, S22-31; discussion S43-54.
25. Dutta, R., McDonough, J., Yin, X., Peterson, J., Chang, A., Torres, T., Gudz, T., Macklin, W.B., Lewis, D.A., Fox, R.J., Rudick, R., Mirnics, K. & Trapp, B.D. (2006) Mitochondrial dysfunction as a cause of axonal degeneration in multiple sclerosis patients. Ann. Neurol., 59, 478-489.
26. Esquifino, A.I., Cano, P., Jimenez, V., Cutrera, R.A. & Cardinali, D.P. (2004) Experimental allergic encephalomyelitis in male Lewis rats subjected to calorie restriction. J. Physiol. Biochem., 60, 245-252.
27. Esquifino, A.I., Cano, P., Jimenez-Ortega, V., Fernandez-Mateos, M.P. & Cardinali, D.P. (2007) Immune response after experimental allergic encephalomyelitis in rats subjected to calorie restriction. J. Neuroinflammation, 4, 6.
28. Finley, L.W., Carracedo, A., Lee, J., Souza, A., Egia, A., Zhang, J., Teruya-Feldstein, J., Moreira, P.I., Cardoso, S.M., Clish, C.B., Pandolfi, P.P. & Haigis, M.C. (2011) SIRT3 opposes reprogramming of cancer cell metabolism through HIF1alpha destabilization. Cancer Cell, 19, 416-428.
29. Fourcade, S., Lopez-Erauskin, J., Galino, J., Duval, C., Naudi, A., Jove, M., Kemp, S., Villarroya, F., Ferrer, I., Pamplona, R., Portero-Otin, M. & Pujol, A. (2008) Early oxidative damage underlying neurodegeneration in X-adrenoleukodystrophy. Hum. Mol. Genet., 17, 1762-1773.
30. Frye, R.A. (1999) Characterization of five human cDNAs with homology to the yeast SIR2 gene: Sir2-like proteins (sirtuins) metabolize NAD and may have protein ADP-ribosyltransferase activity. Biochem. Biophys. Res. Commun., 260, 273-279.
31. Galli, M., Van Gool, F. & Leo, O. (2011) Sirtuins and inflammation: friends or foes? Biochem. Pharmacol., 81, 569-576.
32. Glorioso, C., Oh, S., Douillard, G.G. & Sibille, E. (2011) Brain molecular aging, promotion of neurological disease and modulation by sirtuin 5 longevity gene polymorphism. Neurobiol. Dis., 41, 279-290.
33. Gonsette, R.E. (2008) Neurodegeneration in multiple sclerosis: the role of oxidative stress and excitotoxicity. J. Neurol. Sci., 274, 48-53.
34. Gray, E., Thomas, T.L., Betmouni, S., Scolding, N. & Love, S. (2008) Elevated activity and microglial expression of myeloperoxidase in demyelinated cerebral cortex in multiple sclerosis. Brain Pathol., 18, 86-95.
35. Gray, E., Ginty, M., Kemp, K., Scolding, N. & Wilkins, A. (2011) Peroxisome proliferator-activated receptor-alpha agonists protect cortical neurons from inflammatory mediators and improve peroxisomal function. Eur. J. Neurosci., 33, 1421-1432.
36. Haider, L., Fischer, M.T., Frischer, J.M., Bauer, J., Hoftberger, R., Botond, G., Esterbauer, H., Binder, C.J., Witztum, J.L. & Lassmann, H. (2011) Oxidative damage in multiple sclerosis lesions. Brain, 134, 1914-1924.
37. Haigis, M.C. & Sinclair, D.A. (2010) Mammalian sirtuins: biological insights and disease relevance. Annu. Rev. Pathol., 5, 253-295.
38. Haigis, M.C., Mostoslavsky, R., Haigis, K.M., Fahie, K., Christodoulou, D.C., Murphy, A.J., Valenzuela, D.M., Yancopoulos, G.D., Karow, M., Blander, G., Wolberger, C., Prolla, T.A., Weindruch, R., Alt, F.W. & Guarente, L. (2006) SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells. Cell, 126, 941-954.
39. Hallows, W.C., Lee, S. & Denu, J.M. (2006) Sirtuins deacetylate and activate mammalian acetyl-CoA synthetases. Proc. Natl Acad. Sci. U.S.A., 103, 10230-10235.
40. Harting, K. & Knoll, B. (2010) SIRT2-mediated protein deacetylation: an emerging key regulator in brain physiology and pathology. Eur. J. Cell Biol., 89, 262-269.
41. Hiratsuka, M., Inoue, T., Toda, T., Kimura, N., Shirayoshi, Y., Kamitani, H., Watanabe, T., Ohama, E., Tahimic, C.G., Kurimasa, A. & Oshimura, M. (2003) Proteomics-based identification of differentially expressed genes in human gliomas: down-regulation of SIRT2 gene. Biochem. Biophys. Res. Commun., 309, 558-566.
42. Hirschey, M.D., Shimazu, T., Goetzman, E., Jing, E., Schwer, B., Lombard, D.B., Grueter, C.A., Harris, C., Biddinger, S., Ilkayeva, O.R., Stevens, R.D., Li, Y., Saha, A.K., Ruderman, N.B., Bain, J.R., Newgard, C.B., Farese, R.V. Jr, Alt, F.W., Kahn, C.R. & Verdin, E. (2010) SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation. Nature, 464, 121-125.
43. Hisahara, S., Chiba, S., Matsumoto, H., Tanno, M., Yagi, H., Shimohama, S., Sato, M. & Horio, Y. (2008) Histone deacetylase SIRT1 modulates neuronal differentiation by its nuclear translocation. Proc. Natl Acad. Sci. U.S.A., 105, 15599-15604.
44. van Horssen, J., Witte, M.E., Schreibelt, G. & de Vries, H.E. (2011) Radical changes in multiple sclerosis pathogenesis. Biochim. Biophys. Acta, 1812, 141-150.
45. Imai, S. & Guarente, L. (2010) Ten years of NAD-dependent SIR2 family deacetylases: implications for metabolic diseases. Trends Pharmacol. Sci., 31, 212-220.
46. Imai, S., Armstrong, C.M., Kaeberlein, M. & Guarente, L. (2000) Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature, 403, 795-800.
47. Jastorff, A.M., Haegler, K., Maccarrone, G., Holsboer, F., Weber, F., Ziemssen, T. & Turck, C.W. (2009) Regulation of proteins mediating neurodegeneration in experimental autoimmune encephalomyelitis and multiple sclerosis. Proteomics Clin. Appl., 3, 1273-1287.
48. Jeong, H., Cohen, D.E., Cui, L., Supinski, A., Savas, J.N., Mazzulli, J.R., Yates, J.R. 3rd, Bordone, L., Guarente, L. & Krainc, D. (2012) Sirt1 mediates neuroprotection from mutant huntingtin by activation of the TORC1 and CREB transcriptional pathway. Nat. Med., 18, 159-165.
49. Jiang, M., Wang, J., Fu, J., Du, L., Jeong, H., West, T., Xiang, L., Peng, Q., Hou, Z., Cai, H., Seredenina, T., Arbez, N., Zhu, S., Sommers, K., Qian, J., Zhang, J., Mori, S., Yang, X.W., Tamashiro, K.L., Aja, S., Moran, T.H., Luthi-Carter, R., Martin, B., Maudsley, S., Mattson, M.P., Cichewicz, R.H., Ross, C.A., Holtzman, D.M., Krainc, D. & Duan, W. (2012) Neuroprotective role of Sirt1 in mammalian models of Huntington's disease through activation of multiple Sirt1 targets. Nat. Med., 18, 153-158.
50. Jing, E., Emanuelli, B., Hirschey, M.D., Boucher, J., Lee, K.Y., Lombard, D., Verdin, E.M. & Kahn, C.R. (2011) Sirtuin-3 (Sirt3) regulates skeletal muscle metabolism and insulin signaling via altered mitochondrial oxidation and reactive oxygen species production. Proc. Natl Acad. Sci. U.S.A., 108, 14608-14613.
51. Kaeberlein, M., McVey, M. & Guarente, L. (1999) The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev., 13, 2570-2580.
52. Kalman, B., Laitinen, K. & Komoly, S. (2007) The involvement of mitochondria in the pathogenesis of multiple sclerosis. J. Neuroimmunol., 188, 1-12.
53. Kaneko, S., Wang, J., Kaneko, M., Yiu, G., Hurrell, J.M., Chitnis, T., Khoury, S.J. & He, Z. (2006) Protecting axonal degeneration by increasing nicotinamide adenine dinucleotide levels in experimental autoimmune encephalomyelitis models. J. Neurosci., 26, 9794-9804.
54. Kanfi, Y., Peshti, V., Gozlan, Y.M., Rathaus, M., Gil, R. & Cohen, H.Y. (2008a) Regulation of SIRT1 protein levels by nutrient availability. FEBS Lett., 582, 2417-2423.
55. Kanfi, Y., Shalman, R., Peshti, V., Pilosof, S.N., Gozlan, Y.M., Pearson, K.J., Lerrer, B., Moazed, D., Marine, J.C., de Cabo, R. & Cohen, H.Y. (2008b) Regulation of SIRT6 protein levels by nutrient availability. FEBS Lett., 582, 543-548.
56. Karaca, M., Frigerio, F. & Maechler, P. (2011) From pancreatic islets to central nervous system, the importance of glutamate dehydrogenase for the control of energy homeostasis. Neurochem. Int., 59, 510-517.
57. Kemp, K., Hares, K., Mallam, E., Heesom, K.J., Scolding, N. & Wilkins, A. (2010) Mesenchymal stem cell-secreted superoxide dismutase promotes cerebellar neuronal survival. J. Neurochem., 114, 1569-1580.
58. Kim, S.C., Sprung, R., Chen, Y., Xu, Y., Ball, H., Pei, J., Cheng, T., Kho, Y., Xiao, H., Xiao, L., Grishin, N.V., White, M., Yang, X.J. & Zhao, Y. (2006) Substrate and functional diversity of lysine acetylation revealed by a proteomics survey. Mol. Cell, 23, 607-618.
59. Kim, H.S., Patel, K., Muldoon-Jacobs, K., Bisht, K.S., Aykin-Burns, N., Pennington, J.D., van der Meer, R., Nguyen, P., Savage, J., Owens, K.M., Vassilopoulos, A., Ozden, O., Park, S.H., Singh, K.K., Abdulkadir, S.A., Spitz, D.R., Deng, C.X. & Gius, D. (2010) SIRT3 is a mitochondria-localized tumor suppressor required for maintenance of mitochondrial integrity and metabolism during stress. Cancer Cell, 17, 41-52.
60. Kim, S.H., Lu, H.F. & Alano, C.C. (2011) Neuronal Sirt3 protects against excitotoxic injury in mouse cortical neuron culture. PLoS One, 6, e14731.
61. Kyrylenko, S., Kyrylenko, O., Suuronen, T. & Salminen, A. (2003) Differential regulation of the Sir2 histone deacetylase gene family by inhibitors of class I and II histone deacetylases. Cell. Mol. Life Sci., 60, 1990-1997.
62. Lakshminarasimhan, M. & Steegborn, C. (2011) Emerging mitochondrial signaling mechanisms in physiology, aging processes, and as drug targets. Exp. Gerontol., 46, 174-177.
63. Landry, J., Sutton, A., Tafrov, S.T., Heller, R.C., Stebbins, J., Pillus, L. & Sternglanz, R. (2000) The silencing protein SIR2 and its homologs are NAD-dependent protein deacetylases. Proc. Natl Acad. Sci. U.S.A., 97, 5807-5811.
64. Lassmann, H. & van Horssen, J. (2011) The molecular basis of neurodegeneration in multiple sclerosis. FEBS Lett., 585, 3715-3723.
65. Law, I.K., Liu, L., Xu, A., Lam, K.S., Vanhoutte, P.M., Che, C.M., Leung, P.T. & Wang, Y. (2009) Identification and characterization of proteins interacting with SIRT1 and SIRT3: implications in the anti-aging and metabolic effects of sirtuins. Proteomics, 9, 2444-2456.
66. Lee, I.H., Cao, L., Mostoslavsky, R., Lombard, D.B., Liu, J., Bruns, N.E., Tsokos, M., Alt, F.W. & Finkel, T. (2008) A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy. Proc. Natl Acad. Sci. U.S.A., 105, 3374-3379.
67. Levine, B. & Kroemer, G. (2008) Autophagy in the pathogenesis of disease. Cell, 132, 27-42.
68. Lin, S.J., Ford, E., Haigis, M., Liszt, G. & Guarente, L. (2004) Calorie restriction extends yeast life span by lowering the level of NADH. Genes Dev., 18, 12-16.
69. Lombard, D.B., Alt, F.W., Cheng, H.L., Bunkenborg, J., Streeper, R.S., Mostoslavsky, R., Kim, J., Yancopoulos, G., Valenzuela, D., Murphy, A., Yang, Y., Chen, Y., Hirschey, M.D., Bronson, R.T., Haigis, M., Guarente, L.P., Farese, R.V. Jr, Weissman, S., Verdin, E. & Schwer, B. (2007) Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation. Mol. Cell. Biol., 27, 8807-8814.
70. van Loosdregt, J., Vercoulen, Y., Guichelaar, T., Gent, Y.Y., Beekman, J.M., van Beekum, O., Brenkman, A.B., Hijnen, D.J., Mutis, T., Kalkhoven, E., Prakken, B.J. & Coffer, P.J. (2010) Regulation of Treg functionality by acetylation-mediated Foxp3 protein stabilization. Blood, 115, 965-974.
71. van Loosdregt, J., Brunen, D., Fleskens, V., Pals, C.E., Lam, E.W. & Coffer, P.J. (2011) Rapid temporal control of foxp3 protein degradation by sirtuin-1. PLoS One, 6, e19047.
72. Lopez-Erauskin, J., Fourcade, S., Galino, J., Ruiz, M., Schluter, A., Naudi, A., Jove, M., Portero-Otin, M., Pamplona, R., Ferrer, I. & Pujol, A. (2011) Antioxidants halt axonal degeneration in a mouse model of X-adrenoleukodystrophy. Ann. Neurol., 70, 84-92.
73. Lovato, L., Cianti, R., Gini, B., Marconi, S., Bianchi, L., Armini, A., Anghileri, E., Locatelli, F., Paoletti, F., Franciotta, D., Bini, L. & Bonetti, B. (2008) Transketolase and 2′, 3′-cyclic-nucleotide 3′-phosphodiesterase type I isoforms are specifically recognized by IgG autoantibodies in multiple sclerosis patients. Mol. Cell. Proteomics, 7, 2337-2349.
74. Luthi-Carter, R., Taylor, D.M., Pallos, J., Lambert, E., Amore, A., Parker, A., Moffitt, H., Smith, D.L., Runne, H., Gokce, O., Kuhn, A., Xiang, Z., Maxwell, M.M., Reeves, S.A., Bates, G.P., Neri, C., Thompson, L.M., Marsh, J.L. & Kazantsev, A.G. (2010) SIRT2 inhibition achieves neuroprotection by decreasing sterol biosynthesis. Proc. Natl Acad. Sci. U.S.A., 107, 7927-7932.
75. Mahad, D.J., Ziabreva, I., Campbell, G., Lax, N., White, K., Hanson, P.S., Lassmann, H. & Turnbull, D.M. (2009) Mitochondrial changes within axons in multiple sclerosis. Brain, 132, 1161-1174.
76. Mao, P. & Reddy, P.H. (2010) Is multiple sclerosis a mitochondrial disease? Biochim. Biophys. Acta, 1802, 66-79.
77. Matysiak, M., Stasiolek, M., Orlowski, W., Jurewicz, A., Janczar, S., Raine, C.S. & Selmaj, K. (2008) Stem cells ameliorate EAE via an indoleamine 2, 3-dioxygenase (IDO) mechanism. J. Neuroimmunol., 193, 12-23.
78. Michishita, E., Park, J.Y., Burneskis, J.M., Barrett, J.C. & Horikawa, I. (2005) Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins. Mol. Biol. Cell, 16, 4623-4635.
79. Nakagawa, T., Lomb, D.J., Haigis, M.C. & Guarente, L. (2009) SIRT5 deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle. Cell, 137, 560-570.
80. Nakamura, T. & Lipton, S.A. (2011) S-nitrosylation of critical protein thiols mediates protein misfolding and mitochondrial dysfunction in neurodegenerative diseases. Antioxid. Redox Signal., 14, 1479-1492.
81. Nikic, I., Merkler, D., Sorbara, C., Brinkoetter, M., Kreutzfeldt, M., Bareyre, F.M., Bruck, W., Bishop, D., Misgeld, T. & Kerschensteiner, M. (2011) A reversible form of axon damage in experimental autoimmune encephalomyelitis and multiple sclerosis. Nat. Med., 17, 495-U135.
82. Ogura, M., Nakamura, Y., Tanaka, D., Zhuang, X., Fujita, Y., Obara, A., Hamasaki, A., Hosokawa, M. & Inagaki, N. (2010) Overexpression of SIRT5 confirms its involvement in deacetylation and activation of carbamoyl phosphate synthetase 1. Biochem. Biophys. Res. Commun., 393, 73-78.
83. Ott, M., Demisch, L., Engelhardt, W. & Fischer, P.A. (1993) 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., 241, 108-114.
84. Ou, X., Chae, H.D., Wang, R.H., Shelley, W.C., Cooper, S., Taylor, T., Kim, Y.J., Deng, C.X., Yoder, M.C. & Broxmeyer, H.E. (2011) SIRT1 deficiency compromises mouse embryonic stem cell hematopoietic differentiation, and embryonic and adult hematopoiesis in the mouse. Blood, 117, 440-450.
85. Outeiro, T.F., Kontopoulos, E., Altmann, S.M., Kufareva, I., Strathearn, K.E., Amore, A.M., Volk, C.B., Maxwell, M.M., Rochet, J.C., McLean, P.J., Young, A.B., Abagyan, R., Feany, M.B., Hyman, B.T. & Kazantsev, A.G. (2007) Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson's disease. Science, 317, 516-519.
86. Palacios, O.M., Carmona, J.J., Michan, S., Chen, K.Y., Manabe, Y., Ward, J.L. 3rd, Goodyear, L.J. & Tong, Q. (2009) Diet and exercise signals regulate SIRT3 and activate AMPK and PGC-1alpha in skeletal muscle. Aging (Albany NY), 1, 771-783.
87. Palacios, J.A., Herranz, D., De Bonis, M.L., Velasco, S., Serrano, M. & Blasco, M.A. (2010) SIRT1 contributes to telomere maintenance and augments global homologous recombination. J. Cell Biol., 191, 1299-1313.
88. Patrizia, D., Giuseppina, R., Luisa, P.M., Giuseppe, P. & Dina, B. (2012) SIR, 3(gene), expression.
89. Pennisi, G., Cornelius, C., Cavallaro, M.M., Salinaro, A.T., Cambria, M.T., Pennisi, M., Bella, R., Milone, P., Ventimiglia, B., Migliore, M.R., Di Renzo, L., De Lorenzo, A. & Calabrese, V. (2011) Redox regulation of cellular stress response in multiple sclerosis. Biochem. Pharmacol., 82, 1490-1499.
90. Pfister, J.A., Ma, C., Morrison, B.E. & D'Mello, S.R. (2008) Opposing effects of sirtuins on neuronal survival: SIRT1-mediated neuroprotection is independent of its deacetylase activity. PLoS One, 3, e4090.
91. Piccio, L., Stark, J.L. & Cross, A.H. (2008) Chronic calorie restriction attenuates experimental autoimmune encephalomyelitis. J. Leukoc. Biol., 84, 940-948.
92. Pillai, V.B., Sundaresan, N.R., Kim, G., Gupta, M., Rajamohan, S.B., Pillai, J.B., Samant, S., Ravindra, P.V., Isbatan, A. & Gupta, M.P. (2010) Exogenous NAD blocks cardiac hypertrophic response via activation of the SIRT3-LKB1-AMP-activated kinase pathway. J. Biol. Chem., 285, 3133-3144.
93. Prozorovski, T., Schulze-Topphoff, U., Glumm, R., Baumgart, J., Schroter, F., Ninnemann, O., Siegert, E., Bendix, I., Brustle, O., Nitsch, R., Zipp, F. & Aktas, O. (2008) Sirt1 contributes critically to the redox-dependent fate of neural progenitors. Nat. Cell Biol., 10, 385-394.
94. Qiu, X., Brown, K., Hirschey, M.D., Verdin, E. & Chen, D. (2010) Calorie restriction reduces oxidative stress by SIRT3-mediated SOD2 activation. Cell Metab., 12, 662-667.
95. Rafalski, V.A. & Brunet, A. (2011) Energy metabolism in adult neural stem cell fate. Prog. Neurobiol., 93, 182-203.
96. Rine, J. & Herskowitz, I. (1987) Four genes responsible for a position effect on expression from HML and HMR in Saccharomyces cerevisiae. Genetics, 116, 9-22.
97. Rogina, B. & Helfand, S.L. (2004) Sir2 mediates longevity in the fly through a pathway related to calorie restriction. Proc. Natl Acad. Sci. U.S.A., 101, 15998-16003.
98. Sanders, B.D., Jackson, B. & Marmorstein, R. (2010) Structural basis for sirtuin function: what we know and what we don't. Biochim. Biophys. Acta, 1804, 1604-1616.
99. Scalfari, A., Neuhaus, A., Daumer, M., Ebers, G.C. & Muraro, P.A. (2011) Age and disability accumulation in multiple sclerosis. Neurology, 77, 1246-1252.
100. Schlicker, C., Gertz, M., Papatheodorou, P., Kachholz, B., Becker, C.F. & Steegborn, C. (2008) Substrates and regulation mechanisms for the human mitochondrial sirtuins Sirt3 and Sirt5. J. Mol. Biol., 382, 790-801.
101. Schwer, B., Eckersdorff, M., Li, Y., Silva, J.C., Fermin, D., Kurtev, M.V., Giallourakis, C., Comb, M.J., Alt, F.W. & Lombard, D.B. (2009) Calorie restriction alters mitochondrial protein acetylation. Aging Cell, 8, 604-606.
102. Seo, J.S., Moon, M.H., Jeong, J.K., Seol, J.W., Lee, Y.J., Park, B.H. & Park, S.Y. (2012) SIRT1, a histone deacetylase, regulates prion protein-induced neuronal cell death. Neurobiol. Aging, 33, 1110-1120.
103. Shen, S., Sandoval, J., Swiss, V.A., Li, J., Dupree, J., Franklin, R.J. & Casaccia-Bonnefil, P. (2008) Age-dependent epigenetic control of differentiation inhibitors is critical for remyelination efficiency. Nat. Neurosci., 11, 1024-1034.
104. Shi, T., Fan, G.Q. & Xiao, S.D. (2010) SIRT3 reduces lipid accumulation via AMPK activation in human hepatic cells. J. Dig. Dis., 11, 55-62.
105. Shindler, K.S., Ventura, E., Rex, T.S., Elliott, P. & Rostami, A. (2007) SIRT1 activation confers neuroprotection in experimental optic neuritis. Invest. Ophthalmol. Vis. Sci., 48, 3602-3609.
106. Shindler, K.S., Ventura, E., Dutt, M., Elliott, P., Fitzgerald, D.C. & Rostami, A. (2010) Oral resveratrol reduces neuronal damage in a model of multiple sclerosis. J. Neuroophthalmol., 30, 328-339.
107. Shulga, N., Wilson-Smith, R. & Pastorino, J.G. (2010) Sirtuin-3 deacetylation of cyclophilin D induces dissociation of hexokinase II from the mitochondria. J. Cell Sci., 123, 894-902.
108. Sim, F.J., Zhao, C., Penderis, J. & Franklin, R.J. (2002) The age-related decrease in CNS remyelination efficiency is attributable to an impairment of both oligodendrocyte progenitor recruitment and differentiation. J. Neurosci., 22, 2451-2459.
109. Smith, K.J. (2011) Newly lesioned tissue in multiple sclerosis - a role for oxidative damage? Brain, 134, 1877-1881.
110. Smith, K.J., McDonald, I., Miller, D. & Lassmann, H. (2006). The pathophysiology of multiple sclerosis. In Compston, A., Confavreux, C., Lassmann, H., McDonald, I., Miller, D., Noseworthy, J., Smith, K. & Wekerle, H. (Eds), McAlpine's Multiple Sclerosis. Churchill Livingstone, London, pp. 601-659.
111. Stadelmann, C. (2011) Multiple sclerosis as a neurodegenerative disease: pathology, mechanisms and therapeutic implications. Curr. Opin. Neurol., 24, 224-229.
112. Takeuchi, H., Mizuno, T., Zhang, G., Wang, J., Kawanokuchi, J., Kuno, R. & Suzumura, A. (2005) Neuritic beading induced by activated microglia is an early feature of neuronal dysfunction toward neuronal death by inhibition of mitochondrial respiration and axonal transport. J. Biol. Chem., 280, 10444-10454.
113. Tang, B.L. & Chua, C.E.L. (2008) SIRT2, tubulin deacetylation, and oligodendroglia differentiation. Cell Motil. Cytoskel., 65, 179-182.
114. Tissenbaum, H.A. & Guarente, L. (2001) Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature, 410, 227-230.
115. Valenza, M. & Cattaneo, E. (2010) Neuroprotection and brain cholesterol biosynthesis in Huntington's disease. Proc. Natl Acad. Sci. U.S.A., 107, E143; author reply 144.
116. Verdin, E., Hirschey, M.D., Finley, L.W. & Haigis, M.C. (2010) Sirtuin regulation of mitochondria: energy production, apoptosis, and signaling. Trends Biochem. Sci., 35, 669-675.
117. Wang, L.Q., Colodner, K.J. & Feany, M.B. (2011) Protein misfolding and oxidative stress promote glial-mediated neurodegeneration in an Alexander disease model. J. Neurosci., 31, 2868-2877.
118. Weindruch, R., Naylor, P.H., Goldstein, A.L. & Walford, R.L. (1988) Influences of aging and dietary restriction on serum thymosin alpha 1 levels in mice. J. Gerontol., 43, B40-42.
119. Witherick, J., Wilkins, A., Scolding, N. & Kemp, K. (2010) Mechanisms of oxidative damage in multiple sclerosis and a cell therapy approach to treatment. Autoimmune Dis., 2011, 164608.
120. Witte, M.E., Bo, L., Rodenburg, R.J., Belien, J.A., Musters, R., Hazes, T., Wintjes, L.T., Smeitink, J.A., Geurts, J.J., De Vries, H.E., van der Valk, P. & van Horssen, J. (2009) Enhanced number and activity of mitochondria in multiple sclerosis lesions. J. Pathol., 219, 193-204.
121. Yang, H., Yang, T., Baur, J.A., Perez, E., Matsui, T., Carmona, J.J., Lamming, D.W., Souza-Pinto, N.C., Bohr, V.A., Rosenzweig, A., de Cabo, R., Sauve, A.A. & Sinclair, D.A. (2007) Nutrient-sensitive mitochondrial NAD+ levels dictate cell survival. Cell, 130, 1095-1107.
122. Yang, Y., Cimen, H., Han, M.J., Shi, T., Deng, J.H., Koc, H., Palacios, O.M., Montier, L., Bai, Y., Tong, Q. & Koc, E.C. (2010a) NAD+-dependent deacetylase SIRT3 regulates mitochondrial protein synthesis by deacetylation of the ribosomal protein MRPL10. J. Biol. Chem., 285, 7417-7429.
123. Yang, Z.H., Sun, K., Yan, Z.H., Suo, W.H., Fu, G.H. & Lu, Y. (2010b) Panaxynol protects cortical neurons from ischemia-like injury by up-regulation of HIF-1alpha expression and inhibition of apoptotic cascade. Chem. Biol. Interact., 183, 165-171.
124. Yu, J. & Auwerx, J. (2009) The role of sirtuins in the control of metabolic homeostasis. Ann. N. Y. Acad. Sci., 1173(Suppl. 1), E10-19.
125. Yu, J. & Auwerx, J. (2010) Protein deacetylation by SIRT1: an emerging key post-translational modification in metabolic regulation. Pharmacol. Res., 62, 35-41.
126. Zhang, F., Wang, S., Gan, L., Vosler, P.S., Gao, Y., Zigmond, M.J. & Chen, J. (2011) Protective effects and mechanisms of sirtuins in the nervous system. Prog. Neurobiol., 95, 373-395.
127. Zhao, S., Xu, W., Jiang, W., Yu, W., Lin, Y., Zhang, T., Yao, J., Zhou, L., Zeng, Y., Li, H., Li, Y., Shi, J., An, W., Hancock, S.M., He, F., Qin, L., Chin, J., Yang, P., Chen, X., Lei, Q., Xiong, Y. & Guan, K.L. (2010) Regulation of cellular metabolism by protein lysine acetylation. Science, 327, 1000-1004.