Journal of Shanghai Jiaotong University (Science)

, Volume 19, Issue 6, pp 651–662 | Cite as

Sirtuin functions in the brain: From physiological to pathological aspects

  • Jia-xiang Shao (邵家骧)
  • Ting-ting Zhang (张婷婷)
  • Teng-yuan Liu (刘腾远)
  • Yi-zhou Quan (全亦周)
  • Fan Li (李 凡)
  • Jie Liu (刘 杰)
  • Xiao Yang (杨 霄)
  • Qian Xie (谢 谦)
  • Wei-liang Xia (夏伟梁)
Article

Abstract

Sirtuins are a family of nicotinamide adenine dinucleotide (NAD+) dependent deacetylases involved in multiple biological functions including metabolism, inflammation, stress resistance and aging. In mammals, there are seven members (Sirt1—Sirt7), with diversities in their subcellular localizations and enzymatic activities. Here, we review the functions of sirtuins, with a focus on their roles in normal brain physiology such as neural development regulation, body homeostasis maintenance, and memory formation. We also discuss the role of sirtuins in a variety of brain diseases including stroke, Alzheimer’s, Parkinson’s, and motor neuron dysfunction. Because of the emerging functions of sirtuins in brain physiology and pathology, drugs targeting sirtuins may offer potential therapeutic values for brain disorders.

Key words

sirtuin neural development hypothalamic function stroke neurodegeneration 

CLC number

Q 189 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. [1]
    Haigis M C, Sinclair D A. Mammalian sirtuins: Biological insights and disease relevance [J]. Annual Review of Pathology: Mechanisms of Disease, 2010, 5(1): 253–295.Google Scholar
  2. [2]
    Rine J, Herskowitz I. Four genes responsible for a position effect on expression from HML and HMR in saccharomyces cerevisiae [J]. Genetics, 1987, 116(1): 9–22.Google Scholar
  3. [3]
    Michishita E, Park J Y, Burneskis J M, et al. Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins [J]. Molecular Biology of the Cell, 2005, 16(10): 4623–4635.Google Scholar
  4. [4]
    Vaziri H, Dessain S K, ng Eaton E, et al. HSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase [J]. Cell, 2001, 107(2): 149–159.Google Scholar
  5. [5]
    Hisahara S, Chiba S, Matsumoto H, et al. Histone deacetylase SIRT1 modulates neuronal differentiation by its nuclear translocation [J]. Proceedings of the National Academy of Sciences of the United States of America, 2008, 105(40): 15599–15604.Google Scholar
  6. [6]
    Sugino T, Maruyama M, Tanno M, et al. Protein deacetylase SIRT1 in the cytoplasm promotes nerve growth factor-induced neurite outgrowth in PC12 cells [J]. FEBS Letters, 2010, 584(13): 2821–2826.Google Scholar
  7. [7]
    North B J, Marshall B L, Borra M T, et al. The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase [J]. Molecular Cell, 2003, 11(2): 437–444.Google Scholar
  8. [8]
    North B J, Verdin E. Interphase nucleocytoplasmic shuttling and localization of SIRT2 during mitosis [J]. PLoS One, 2007, 2(8): e784.Google Scholar
  9. [9]
    Verdin E, Hirschey M D, Finley LWS, et al. Sirtuin regulation of mitochondria: Energy production, apoptosis, and signaling [J]. Trends in Biochemical Sciences, 2010, 35(12): 669–675.Google Scholar
  10. [10]
    Michishita E, Mccord R A, Berber E, et al. SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin [J]. Nature, 2008, 452(7186): 492–496.Google Scholar
  11. [11]
    Ford E, Voit R, Liszt G, et al. Mammalian Sir2 homolog SIRT7 is an activator of RNA polymerase I transcription [J]. Genes & Development, 2006, 20(9): 1075–1080.Google Scholar
  12. [12]
    Onyango P, Celic I, Mccaffery J M, et al. SIRT3, a human SIR2 homologue, is an NAD-dependent deacetylase localized to mitochondria [J]. Proceedings of the National Academy of Sciences of the United States of America, 2002, 99(21): 13653–13658.Google Scholar
  13. [13]
    Barber M F, Michishita-Kioi E, Xi Y, et al. SIRT7 links H3K18 deacetylation to maintenance of oncogenic transformation [J]. Nature, 2012, 487(7405): 114–118.Google Scholar
  14. [14]
    Haigis M C, Mostoslavsky R, Haigis K M, et al. SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells [J]. Cell, 2006, 126(5): 941–954.Google Scholar
  15. [15]
    Nakagawa T, Lomb D J, Haigis M C, et al. SIRT5 deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle [J]. Cell, 2009, 137(3): 560–570.Google Scholar
  16. [16]
    Du J, Zhou Y, Su X, et al. Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase [J]. Science, 2011, 334(6057): 806–809.Google Scholar
  17. [17]
    Liszt G, Ford E, Kurtev M, et al. Mouse Sir2 homolog SIRT6 is a nuclear ADP-ribosyltransferase [J]. Journal of Biological Chemistry, 2005, 280(22): 21313–21320.Google Scholar
  18. [18]
    Jiang H, Khan S, Wang Y, et al. SIRT6 regulates TNF-α secretion through hydrolysis of longchain fatty acyl lysine [J]. Nature, 2013, 496(7443): 110–113.Google Scholar
  19. [19]
    Feldman J L, Baeza J, Denu J M. Activation of the protein deacetylase SIRT6 by long-chain fatty acids and widespread deacylation by mammalian sirtuins [J]. The Journal of Biological Chemistry, 2013, 288(43): 31350–31356.Google Scholar
  20. [20]
    Guarente L. Calorie restriction and sirtuins revisited [J]. Genes & Development, 2013, 27(19): 2072–2085.Google Scholar
  21. [21]
    Kaeberlein M, Mcvey M, Guarente L. The SIR2/3/4 complex and SIR2 alone promote longevity in saccharomyces cerevisiae by two different mechanisms [J]. Genes & Development, 1999, 13(19): 2570–2580.Google Scholar
  22. [22]
    Chen D, Guarente L. SIR2: A potential target for calorie restriction mimetics [J]. Trends in Molecular Medicine, 2007, 13(2): 64–71.Google Scholar
  23. [23]
    Kanfi Y, Naiman S, Amir G, et al. The sirtuin SIRT6 regulates lifespan in male mice [J]. Nature, 2012, 483(7388): 218–221.Google Scholar
  24. [24]
    Satoh A, Brace C S, Rensing N, et al. Sirt1 extends life span and delays aging in mice through the regulation of Nk2 homeobox 1 in the DMH and LH [J]. Cell Metabolism, 2013, 18(3): 416–430.Google Scholar
  25. [25]
    Hall J A, Dominy J E, Lee Y, et al. The sirtuin family’s role in aging and age-associated pathologies [J]. Journal of Clinical Investigation, 2013, 123(3): 973–979.Google Scholar
  26. [26]
    Kriegstein A, Alvarez-Buylla A. The glial nature of embryonic and adult neural stem cells [J]. Annual Review Neuroscience, 2009, 32(1): 149–184.Google Scholar
  27. [27]
    Prozorovski T, Schulze-Topphoff U, Glumm R, et al. Sirt1 contributes critically to the redoxdependent fate of neural progenitors [J]. Nature Cell Biology, 2008, 10(4): 385–394.Google Scholar
  28. [28]
    Tiberi L, van den Ameele J, Dimidschstein J, et al. BCL6 controls neurogenesis through Sirt1-dependent epigenetic repression of selective Notch targets [J]. Nature Neuroscience, 2012, 15(12): 1627–1635.Google Scholar
  29. [29]
    Ross S E, Greenberg M E, Stiles C D. Basic helix-loop-helix factors in cortical development [J]. Neuron, 2003, 39(1): 13–25.Google Scholar
  30. [30]
    Kageyama R, Ohtsuka T, Kobayashi T. The Hes gene family: Repressors and oscillators that orchestrate embryogenesis [J]. Development, 2007, 134(7): 1243–1251.Google Scholar
  31. [31]
    Ichi S, Boshnjaku V, Shen Y W, et al. Role of Pax3 acetylation in the regulation of Hes1 and Neurog2 [J]. Molecular Biology of the Cell, 2011, 22(4): 503–512.Google Scholar
  32. [32]
    Holloway K R, Calhoun T N, Saxena M, et al. SIRT1 regulates dishevelled proteins and promotes transient and constitutive Wnt signaling [J]. Proceedings of the National Academy of Sciences of the United States of America, 2010, 107(20): 9216–9221.Google Scholar
  33. [33]
    Liu B, Ghosh S, Yang X, et al. Resveratrol rescues SIRT1-dependent adult stem cell decline and alleviates progeroid features in laminopathy-based progeria [J]. Cell Metabolism, 2012, 16(6): 738–750.Google Scholar
  34. [34]
    Zhang Y, Wang J, Chen G, et al. Inhibition of Sirt1 promotes neural progenitors toward motoneuron differentiation from human embryonic stem cells [J]. Biochemical and Biophysical Research Communications, 2011, 404(2): 610–614.Google Scholar
  35. [35]
    Rafalski V A, Ho P P, Brett J O, et al. Expansion of oligodendrocyte progenitor cells following SIRT1 inactivation in the adult brain [J]. Nature Cell Biology, 2013, 15(6): 614–624.Google Scholar
  36. [36]
    Maxwell M M, Tomkinson E M, Nobles J, et al. The sirtuin 2 microtubule deacetylase is an abundant neuronal protein that accumulates in the aging CNS [J]. Human Molecular Genetics, 2011, 20(20): 3986–3996.Google Scholar
  37. [37]
    Werner H B, Kuhlmann K, Shen S, et al. Proteolipid protein is required for transport of sirtuin 2 into CNS myelin [J]. Journal of Neuroscience, 2007, 27(20): 7717–7730.Google Scholar
  38. [38]
    Li W, Zhang B, Tang J, et al. Sirtuin 2, a mammalian homolog of yeast silent information regulator-2 longevity regulator, is an oligodendroglial protein that decelerates cell differentiation through deacetylating α-tubulin [J]. The Journal of Neuroscience, 2007, 27(10): 2606–2616.Google Scholar
  39. [39]
    Ji S, Doucette J R, Nazarali A J. Sirt2 is a novel in vivo downstream target of Nkx2. 2 and enhances oligodendroglial cell differentiation [J]. Journal of Molecular Cell Biology, 2011, 3(6): 351–359.Google Scholar
  40. [40]
    Si X, Chen W, Guo X, et al. Activation of GSK3beta by Sirt2 is required for early lineage commitment of mouse embryonic stem cell [J]. PLoS One, 2013, 8(10): e76699.Google Scholar
  41. [41]
    Beirowski B, Gustin J, Armour S M, et al. Sirtwo-homolog 2 (Sirt2) modulates peripheral myelination through polarity protein Par-3/atypical protein kinase C (aPKC) signaling [J]. Proceedings of the National Academy of Sciences of the United States of America, 2011, 108(43): E952–961.Google Scholar
  42. [42]
    Komlos D, Mann K D, Zhuo Y, et al. Glutamate dehydrogenase 1 and SIRT4 regulate glial development [J]. Glia, 2013, 61(3): 394–408.Google Scholar
  43. [43]
    Guo W, Qian L, Zhang J, et al. Sirt1 overexpression in neurons promotes neurite outgrowth and cell survival through inhibition of the mTOR signaling [J]. Journal of Neuroscience Research, 2011, 89(11): 1723–1736.Google Scholar
  44. [44]
    Li X H, Chen C, Tu Y, et al. Sirt1 promotes axonogenesis by deacetylation of Akt and inactivation of GSK3 [J]. Molecular Neurobiology, 2013, 48(3): 490–499.Google Scholar
  45. [45]
    Liu C M, Wang R Y, Saijilafu , et al. MicroRNA-138 and SIRT1 form a mutual negative feedback loop to regulate mammalian axon regeneration [J]. Genes & Development, 2013, 27(13): 1473–1483.Google Scholar
  46. [46]
    Michan S, Li Y, Chou M M H, et al. SIRT1 is essential for normal cognitive function and synaptic plasticity [J]. The Journal of Neuroscience, 2010, 30(29): 9695–9707.Google Scholar
  47. [47]
    Codocedo J F, Allard C, Godoy J A, et al. SIRT1 regulates dendritic development in hippocampal neurons [J]. PLoS One, 2012, 7(10): e47073.Google Scholar
  48. [48]
    Coppari R. Metabolic actions of hypothalamic SIRT1 [J]. Trends in Endocrinology and Metabolism, 2012, 23(4): 179–185.Google Scholar
  49. [49]
    Ramadori G, Lee C E, Bookout A L, et al. Brain SIRT1: Anatomical distribution and regulation by energy availability [J]. The Journal of Neuroscience, 2008, 28(40): 9989–9996.Google Scholar
  50. [50]
    Ramadori G, Fujikawa T, Fukuda M, et al. SIRT1 deacetylase in POMC neurons is required for homeostatic defenses against diet-induced obesity [J]. Cell Metabolism, 2010, 12(1): 78–87.Google Scholar
  51. [51]
    Ramadori G, Fujikawa T, Erson J, et al. SIRT1 deacetylase in SF1 neurons protects against metabolic imbalance [J]. Cell Metabolism, 2011, 14(3): 301–312.Google Scholar
  52. [52]
    Hong S H, Lee K S, Kwak S J, et al. Minibrain/dyrk1a regulates food intake through the Sir2-FOXO-sNPF/NPY pathway in drosophila and mammals [J]. PLoS Genetics, 2012, 8(8): e1002857.Google Scholar
  53. [53]
    Cakir I, Perello M, Lansari O, et al. Hypothalamic Sirt1 regulates food intake in a rodent model system [J]. PLoS One, 2009, 4(12): e8322.Google Scholar
  54. [54]
    Veláquez D A, Martinez G, Romero A, et al. The central Sirtuin 1/p53 pathway is essential for the orexigenic action of ghrelin [J]. Diabetes, 2011, 60(4): 1177–1185.Google Scholar
  55. [55]
    Dietrich M O, Antunes C, Geliang G, et al. Agrp neurons mediate Sirt1’s action on the melanocortin system and energy balance: Roles for Sirt1 in neuronal firing and synaptic plasticity [J]. The Journal of Neuroscience, 2010, 30(35): 11815–11825.Google Scholar
  56. [56]
    Asher G, Gatfield D, Stratmann M, et al. SIRT1 regulates circadian clock gene expression through PER2 deacetylation [J]. Cell, 2008, 134(2): 317–328.Google Scholar
  57. [57]
    Nakahata Y, Kaluzova M, Grimaldi B, et al. The NAD+-dependent deacetylase SIRT1 modulates CLOCK-mediated chromatin remodeling and circadian control [J]. Cell, 2008, 134(2): 329–340.Google Scholar
  58. [58]
    Chang H C, Guarente L. SIRT1 mediates central circadian control in the SCN by a mechanism that decays with aging [J]. Cell, 2013, 153(7): 1448–1460.Google Scholar
  59. [59]
    Panossian L, Fenik P, Zhu Y, et al. SIRT1 regulation of wakefulness and senescence-like phenotype in wake neurons [J]. The Journal of Neuroscience, 2011, 31(11): 4025–4036.Google Scholar
  60. [60]
    Peek C B, Affinati A H, Ramsey KM, et al. Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism in mice [J]. Science, 2013, 342(6158):1243417.Google Scholar
  61. [61]
    Monteserin-Garcia J, Al-Massadi O, Seoane L M, et al. Sirt1 inhibits the transcription factor CREB to regulate pituitary growth hormone synthesis [J]. FASEB Journal, 2013, 27(4): 1561–1571.Google Scholar
  62. [62]
    Schwer B, Schumacher B, Lombard D B, et al. Neural sirtuin 6 (Sirt6) ablation attenuates somatic growth and causes obesity [J]. Proceedings of the National Academy of Sciences of the United States of America, 2010, 107(50): 21790–21794.Google Scholar
  63. [63]
    Ferguson D, Koo J W, Feng J, et al. Essential role of SIRT1 signaling in the nucleus accumbens in cocaine and morphine action [J]. The Journal of Neuroscience, 2013, 33(41): 16088–16098.Google Scholar
  64. [64]
    Libert S, Pointer K, Bell E L, et al. SIRT1 activates MAO-A in the brain to mediate anxiety and exploratory drive [J]. Cell, 2011, 147(7): 1459–1472.Google Scholar
  65. [65]
    Gao J, Wang W Y, Mao Y W, et al. A novel pathway regulates memory and plasticity via SIRT1 and miR-134 [J]. Nature, 2010, 466(7310): 1105–1109.Google Scholar
  66. [66]
    Zhao Y N, Li W F, Li F, et al. Resveratrol improves learning and memory in normally aged mice through microRNA-CREB pathway [J]. Biochemical and Biophysical Research Communications, 2013, 435(4): 597–602.Google Scholar
  67. [67]
    Qiu X, Brown K, Hirschey M D, et al. Calorie restriction reduces oxidative stress by SIRT3-mediated SOD2 activation [J]. Cell Metabolism, 2010, 12(6): 662–667.Google Scholar
  68. [68]
    Lin Z F, Xu H B, Wang J Y, et al. SIRT5 desuccinylates and activates SOD1 to eliminate ROS [J]. Biochemical and Biophysical Research Communications, 2013, 441(1): 191–195.Google Scholar
  69. [69]
    Hsu C P, Zhai P, Yamamoto T, et al. Silent information regulator 1 protects the heart from ischemia/reperfusion [J]. Circulation, 2010, 122(21): 2170–2182.Google Scholar
  70. [70]
    Nadtochiy S M, Yao H, Mcburney M W, et al. SIRT1-mediated acute cardioprotection [J]. American Journal of Physiology-Heart and Circulatory Physiology, 2011, 301(4): H1506–H1512.Google Scholar
  71. [71]
    Sundaresan N R, Gupta M, Kim G, et al. Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice [J]. The Journal of Clinical Investigation, 2009, 119(9): 2758–2771.Google Scholar
  72. [72]
    Sundaresan N R, Vasudevan P, Zhong L, et al. The sirtuin SIRT6 blocks IGF-Akt signaling and development of cardiac hypertrophy by targeting c-Jun [J]. Nature Medicine, 2012, 18(11): 1643–1650.Google Scholar
  73. [73]
    Vakhrusheva O, Smolka C, Gajawada P, et al. Sirt7 increases stress resistance of cardiomyocytes and prevents apoptosis and inflammatory cardiomyopathy in mice [J]. Circulation Research, 2008, 102(6): 703–710.Google Scholar
  74. [74]
    Narayan N, Lee I H, Borenstein R, et al. The NAD-dependent deacetylase SIRT2 is required for programmed necrosis [J]. Nature, 2012, 492(7428): 199–204.Google Scholar
  75. [75]
    Newton K, Hildebrand J M, Shen Z, et al. Is SIRT2 required for necroptosis? [J]. Nature, 2014, 506(7489): E4–E6.Google Scholar
  76. [76]
    Narayan N, Lee I H, Borenstein R, et al. Retraction: The NAD-dependent deacetylase SIRT2 is required for programmed necrosis [J]. Nature, 2014, 506(7489): 516.Google Scholar
  77. [77]
    Morris K C, Lin H W, Thompson J W, et al. Pathways for ischemic cytoprotection: Role of sirtuins in caloric restriction, resveratrol, and ischemic preconditioning [J]. Journal of Cerebral Blood Flow & Metabolism, 2011, 31(4): 1003–1019.Google Scholar
  78. [78]
    Della-Morte D, Dave K R, Defazio R A, et al. Resveratrol pretreatment protects rat brain from cerebral ischemic damage via a sirtuin 1-uncoupling protein 2 pathway [J]. Neuroscience, 2009, 159(3): 993–1002.Google Scholar
  79. [79]
    Clark D, Tuor U I, Thompson R, et al. Protection against recurrent stroke with resveratrol:Endothelial protection [J]. PLoS One, 2012, 7(10): e47792.Google Scholar
  80. [80]
    Wang L, Zhang L, Chen Z B, et al. Icariin enhances neuronal survival after oxygen and glucose deprivation by increasing SIRT1 [J]. European Journal of Pharmacology, 2009, 609(1–3): 40–44.Google Scholar
  81. [81]
    Zhu H R, Wang Z Y, Zhu X L, et al. Icariin protects against brain injury by enhancing SIRT1-dependent PGC-1α expression in experimental stroke [J]. Neuropharmacology, 2010, 59(1–2): 70–76.Google Scholar
  82. [82]
    Raval A P, Dave K R, Péez-Pinzón M A. Resveratrol mimics ischemic preconditioning in the brain [J]. Journal of Cerebral Blood Flow & Metabolism, 2006, 26(9): 1141–1147.Google Scholar
  83. [83]
    Yan W, Fang Z, Yang Q, et al. SirT1 mediates hyperbaric oxygen preconditioning-induced ischemic tolerance in rat brain [J]. Journal of Cerebral Blood Flow & Metabolism, 2013, 33(3): 396–406.Google Scholar
  84. [84]
    Wang P, Xu T Y, Guan Y F, et al. Nicotinamide phosphoribosyltransferase protects against ischemic stroke through SIRT1-dependent adenosine monophosphate-activated kinase pathway [J]. Annals of Neurology, 2011, 69(2): 360–374.Google Scholar
  85. [85]
    Wang P, Guan Y F, Du H, et al. Induction of autophagy contributes to the neuroprotection of nicotinamide phosphoribosyltransferase in cerebral ischemia [J]. Autophagy, 2012, 8(1): 77–87.Google Scholar
  86. [86]
    Hernández-Jiménez M, Hurtado O, Cuartero M I, et al. Silent information regulator 1 protects the brain against cerebral ischemic damage [J]. Stroke, 2013, 44(8): 2333–2337.Google Scholar
  87. [87]
    Lee O H, Kim J, Kim J M, et al. Decreased expression of sirtuin 6 is associated with release of high mobility group box-1 after cerebral ischemia [J]. Biochemical and Biophysical Research Communications, 2013, 438(2): 388–394.Google Scholar
  88. [88]
    Qin W, Yang T, Ho L, et al. Neuronal SIRT1 activation as a novel mechanism underlying the prevention of Alzheimer disease amyloid neuropathology by calorie restriction [J]. The Journal of Biological Chemistry, 2006, 281(31): 21745–21754.Google Scholar
  89. [89]
    Kim D, Nguyen M D, Dobbin M M, et al. SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer’s disease and amyotrophic lateral sclerosis [J]. The EMBO Journal, 2007, 26(13): 3169–3179.Google Scholar
  90. [90]
    Green K N, Steffan J S, Martinez-Coria H, et al. Nicotinamide restores cognition in Alzheimer’s disease transgenic mice via a mechanism involving sirtuin inhibition and selective reduction of Thr231-phosphotau [J]. The Journal of Neuroscience, 2008, 28(45): 11500–11510.Google Scholar
  91. [91]
    Donmez G, Wang D, Cohen D E, et al. SIRT1 suppresses beta-amyloid production by activating the α-secretase gene ADAM10 [J]. Cell, 2010, 142(2): 320–332.Google Scholar
  92. [92]
    Wang R, Li J J, Diao S, et al. Metabolic stress modulates Alzheimer’s β-secretase gene transcription via SIRT1-PPARΓ-PGC-1 in neurons [J]. Cell Metabolism, 2013, 17(5): 685–694.Google Scholar
  93. [93]
    Chen J, Zhou Y, Mueller-Steiner S, et al. SIRT1 protects against microglia-dependent amyloid-β toxicity through inhibiting NF-κB signaling [J]. The Journal of Biological Chemistry, 2005, 280(48): 40364–40374.Google Scholar
  94. [94]
    Min S W, Cho S H, Zhou Y, et al. Acetylation of tau inhibits its degradation and contributes to tauopathy [J]. Neuron, 2010, 67(6): 953–966.Google Scholar
  95. [95]
    Kumar R, Chaterjee P, Sharma P K, et al. Sirtuin1: A promising serum protein marker for early detection of Alzheimer’s disease [J]. PLoS One, 2013, 8(4): e61560.Google Scholar
  96. [96]
    Porcelli S, Salfi R, Politis A, et al. Association between sirtuin2 gene rs10410544 polymorphism and depression in Alzheimer’s disease in two independent European samples [J]. Journal of Neural Transmission, 2013, 120(12): 1709–1715.Google Scholar
  97. [97]
    Wei W, Xu X, Li H, et al. The SIRT2 polymorphism rs10410544 and risk of Alzheimer’s disease: A meta-analysis [J]. Neuromolecular Medicine, 2014. DOI 10.1007/s12017-014-8291-0 (published online).Google Scholar
  98. [98]
    Xia M, Yu J T, Miao D, et al. SIRT2 polymorphism rs10410544 is associated with Alzheimer’s disease in a Han Chinese population [J]. Journal of Neurological Sciences, 2014, 336(1–2): 48–51.Google Scholar
  99. [99]
    Polito L, Kehoe P G, Davin A, et al. The SIRT2 polymorphism rs10410544 and risk of Alzheimer’s disease in two Caucasian case-control cohorts [J]. Alzheimers & Dementia, 2013, 9(4): 392–399.Google Scholar
  100. [100]
    Rothgiesser K M, Erener S, Waibel S, et al. SIRT2 regulates NF-κB-dependent gene expression through deacetylation of p65 Lys310 [J]. Journal of Cell Science, 2010, 123(24): 4251–4258.Google Scholar
  101. [101]
    Pais T F, Szego E M, Marques O, et al. The NAD-dependent deacetylase sirtuin 2 is a suppressor of microglial activation and brain inflammation [J]. The EMBO Journal, 2013, 32(19): 2603–2616.Google Scholar
  102. [102]
    Weir H J M, Murray T K, Kehoe P G, et al. CNS SIRT3 expression is altered by reactive oxygen species and in Alzheimer’s disease [J]. PLoS One, 2012, 7(11): e48225.Google Scholar
  103. [103]
    Albani D, Polito L, Batelli S, et al. The SIRT1 activator resveratrol protects SK-N-BE cells from oxidative stress and against toxicity caused by α-synuclein or amyloid-β (1–42) peptide [J]. Journal of Neurochemistry, 2009, 110(5): 1445–1456.Google Scholar
  104. [104]
    Wu Y, Li X, Zhu J X, et al. Resveratrol-activated AMPK/SIRT1/autophagy in cellular models of Parkinson’s disease [J]. Neurosignals, 2011, 19(3): 163–174.MathSciNetGoogle Scholar
  105. [105]
    Blanchet J, Longpre F, Bureau G, et al. Resveratrol, a red wine polyphenol, protects dopaminergic neurons in MPTP-treated mice [J]. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 2008, 32(5): 1243–1250.Google Scholar
  106. [106]
    Donmez G, Arun A, Chung C Y, et al. SIRT1 protects against α-synuclein aggregation by activating molecular chaperones [J]. The Journal of Neuroscience, 2012, 32(1): 124–132.Google Scholar
  107. [107]
    Outeiro T F, Kontopoulos E, Altmann S M, et al. Sirtuin 2 inhibitors rescue α-synuclein-mediated toxicity in models of Parkinson’s disease [J]. Science, 2007, 317(5837): 516–519.Google Scholar
  108. [108]
    Sampaio-Marques B, Felgueiras C, Silva A, et al. SNCA (α-synuclein)-induced toxicity in yeast cells is dependent on sirtuin 2 (Sir2)-mediated mitophagy [J]. Autophagy, 2012, 8(10): 1494–1509.Google Scholar
  109. [109]
    Liu L, Arun A, Ellis L, et al. Sirtuin 2 (SIRT2) enhances 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced nigrostriatal damage via deacetylating forkhead box O3a (Foxo3a) and activating Bim protein [J]. The Journal of Biological Chemistry, 2012, 287(39): 32307–32311.Google Scholar
  110. [110]
    Liu L, Arun A, Ellis L, et al. Additons and corrections: Sirtuin 2 (SIRT2) enhances 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced nigrostriatal damage via deacetylating forkhead box O3a (Foxo3a) and activating Bim protein [J]. The Journal of Biological Chemistry, 2013, 288(33): 24163.Google Scholar
  111. [111]
    Glorioso C, Oh S, Douillard G G, et al. Brain molecular aging, promotion of neurological disease and modulation by Sirtuin5 longevity gene polymorphism [J]. Neurobiology of Disease, 2011, 41(2): 279–290.Google Scholar
  112. [112]
    Pallos J, Bodai L, Lukacsovich T, et al. Inhibition of specific HDACs and sirtuins suppresses pathogenesis in a drosophila model of Huntington’s disease [J]. Human Molecular Genetics, 2008, 17(33): 3767–3775.Google Scholar
  113. [113]
    Parker J A, Arango M, Abderrahmane S, et al. Resveratrol rescues mutant polyglutamine cytotoxicity in nematode and mammalian neurons [J]. Nature Genetics, 2005, 37(4): 349–350.Google Scholar
  114. [114]
    Jiang M, Wang J, Fu J, et al. Neuroprotective role of Sirt1 in mammalian models of Huntington’s disease through activation of multiple Sirt1 targets [J]. Nature Medicine, 2012, 18(1): 153–158.Google Scholar
  115. [115]
    Jeong H, Cohen D E, Cui L, et al. Sirt1 mediates neuroprotection from mutant huntingtin by activation of the TORC1 and CREB transcriptional pathway [J]. Nature Medicine, 2012, 18(1): 159–165.Google Scholar
  116. [116]
    Luthi-Carter R, Taylor D M, Pallos J, et al. SIRT2 inhibition achieves neuroprotection by decreasing sterol biosynthesis [J]. Proceedings of the National Academy of Sciences of the United States of America, 2010, 107(17): 7927–7932.Google Scholar
  117. [117]
    Chopra V, Quinti L, Kim J, et al. The sirtuin 2 inhibitor AK-7 is neuroprotective in Huntington’s disease mouse models [J]. Cell Reports, 2012, 2(6): 1492–1497.Google Scholar
  118. [118]
    Bobrowska A, Donmez G, Weiss A, et al. SIRT2 ablation has no effect on tubulin acetylation in brain, cholesterol biosynthesis or the progression of Huntington’s disease phenotypes in vivo [J]. PLoS One, 2012, 7(4): e34805.Google Scholar
  119. [119]
    Fu J, Jin J, Cichewicz R H, et al. Trans-(-)-epsilonviniferin increases mitochondrial sirtuin3 (SIRT3), activates AMP-activated protein kinase (AMPK), and protects cells in models of Huntington disease [J]. The Journal of Biological Chemistry, 2012, 287(29): 24460–24472.Google Scholar
  120. [120]
    Dobbin M M, Madabhushi R, Pan L, et al. SIRT1 collaborates with ATM and HDAC1 to maintain genomic stability in neurons [J]. Nature Neuroscience, 2013, 16(8): 1008–1015.Google Scholar
  121. [121]
    Li Y, Xu W, Mcburney M W, et al. SirT1 inhibition reduces IGF-I/IRS-2/Ras/ERK1/2 signaling and protects neurons [J]. Cell Metabolism, 2008, 8(1): 38–48.Google Scholar
  122. [122]
    Kim S H, Lu H F, Alano C C. Neuronal Sirt3 protects against excitotoxic injury in mouse cortical neuron culture [J]. PLoS One, 2011, 6(3): e14731.Google Scholar
  123. [123]
    Someya S, Yu W, Hallows W C, et al. Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction [J]. Cell, 2010, 143(5): 802–812.Google Scholar
  124. [124]
    Wang J, Zhang Y, Tang L, et al. Protective effects of resveratrol through the up-regulation of SIRT1 expression in the mutant hSOD1-G93A-bearing motor neuron-like cell culture model of amyotrophic lateral sclerosis [J]. Neuroscience Letters, 2011, 503(3): 250–255.Google Scholar
  125. [125]
    Araki T, Sasaki Y, Milbrandt J. Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration [J]. Science, 2004, 305(5686): 1010–1013.Google Scholar
  126. [126]
    Suzuki K, Koike T. Mammalian Sir2-related protein (SIRT) 2-mediated modulation of resistance to axonal degeneration in slow Wallerian degeneration mice: A crucial role of tubulin deacetylation [J]. Neuroscience, 2007, 147(3): 599–612.Google Scholar
  127. [127]
    Nimmagadda V K, Bever C T, Vattikunta N R, et al. Overexpression of SIRT1 protein in neurons protects against experimental autoimmune encephalomyelitis through activation of multiple SIRT1 targets [J]. The Journal of Immunology, 2013, 190(9): 4595–4607.Google Scholar
  128. [128]
    Bizat N, Peyrin J M, Haik S, et al. Neuron dysfunction is induced by prion protein with an insertional mutation via a Fyn kinase and reversed by sirtuin activation in caenorhabditis elegans [J]. The Journal of Neuroscience, 2010, 30(15): 5394–5403.Google Scholar
  129. [129]
    Seo J S, Moon M H, Jeong J K, et al. SIRT1, a histone deacetylase, regulates prion protein-induced neuronal cell death [J]. Neurobiology of Aging, 2012, 33(6): 1110–1120.Google Scholar
  130. [130]
    Jeong J K, Moon M H, Lee Y J, et al. Autophagy induced by the class III histone deacetylase Sirt1 prevents prion peptide neurotoxicity [J]. Neurobiology of Aging, 2013, 34(1): 146–156.Google Scholar
  131. [131]
    Bodkin N L, Alexander T M, Ortmeyer H K, et al. Mortality and morbidity in laboratory-maintained Rhesus monkeys and effects of long-term dietary restriction [J]. Journals of Gerontology Series A: Biological Sciences & Medical Sciences, 2003, 58(3): 212–219.Google Scholar
  132. [132]
    Mattison J A, Roth G S, Beasley T M, et al. Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study [J]. Nature, 2012, 489(7415): 318–321.Google Scholar
  133. [133]
    Kim H S, Xiao C, Wang R H, et al. Hepatic-specific disruption of SIRT6 in mice results in fatty liver formation due to enhanced glycolysis and triglyceride synthesis [J]. Cell Metabolism, 2010, 12(3): 224–236.Google Scholar
  134. [134]
    Shao J, Liu T, Xie Q R, et al. Adjudin attenuates lipopolysaccharide (LPS)- and ischemia-induced microglial activation [J]. Journal of Neuroimmunology, 2013, 254(1–2): 83–90.Google Scholar
  135. [135]
    Mouchiroud L, Houtkooper R H, Moullan N, et al. The NAD+/sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling [J]. Cell, 2013, 154(2): 430–441.Google Scholar
  136. [136]
    Gomes A P, Price N L, Ling A J Y, et al. Declining NAD+ induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging [J]. Cell, 2013, 155(7): 1624–1638.Google Scholar
  137. [137]
    Yoshino J, Mills K F, Yoon M J, et al. Nicotinamide mononucleotide, a key NAD+ intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice [J]. Cell Metabolism, 2011, 14(4): 528–536.Google Scholar
  138. [138]
    Canto C, Houtkooper R H, Pirinen E, et al. The NAD+ precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat dietinduced obesity [J]. Cell Metabolism, 2012, 15(6): 838–847.Google Scholar

Copyright information

© Shanghai Jiaotong University and Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Jia-xiang Shao (邵家骧)
    • 1
    • 2
    • 3
  • Ting-ting Zhang (张婷婷)
    • 2
    • 3
  • Teng-yuan Liu (刘腾远)
    • 2
    • 3
  • Yi-zhou Quan (全亦周)
    • 1
    • 2
    • 3
  • Fan Li (李 凡)
    • 2
    • 3
  • Jie Liu (刘 杰)
    • 1
    • 2
    • 3
  • Xiao Yang (杨 霄)
    • 2
    • 3
  • Qian Xie (谢 谦)
    • 2
    • 3
  • Wei-liang Xia (夏伟梁)
    • 1
    • 2
    • 3
  1. 1.State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Renji HospitalShanghai Jiaotong University School of MedicineShanghaiChina
  2. 2.School of Biomedical EngineeringShanghai Jiaotong UniversityShanghaiChina
  3. 3.Med-X Research InstituteShanghai Jiaotong UniversityShanghaiChina

Personalised recommendations