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Targeting Sirtuin-1 in Huntington’s Disease: Rationale and Current Status

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Abstract

Huntington’s disease (HD) is an autosomal dominant hereditary disease caused by a trinucleotide repeat mutation in the huntingtin gene that results in an increased number of glutamine residues in the N terminus of huntingtin protein. Mutant huntingtin leads to progressive impairment of motor function, cognitive dysfunction, and neuropsychiatric disturbance. There are no disease-modifying treatments available. During the past decade, sirtuin-1 (SIRT1) has been the focus of intense investigation and discussion because it regulates longevity in multiple organisms and has shown beneficial effects in a variety of models of neurodegenerative disorders. Studies in different animal models provide convincing evidence that SIRT1 protects neurons in mouse models of HD as well as in Caenorhabditis elegans, although controversial results were reported in a fly model. Indeed, many connections exist between the deacetylation function of SIRT1 and its role in neuroprotection. As a result, pharmacological interventions targeting SIRT1 might become promising strategies to combat HD. This review summarizes recent progress in SIRT1 research, with a focus on the specificity of this protein as a potential therapeutic target for HD, as well as existing challenges for developing SIRT1 modulators for clinical use.

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References

  1. The Huntington’s Disease Collaborative Research Group. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. Cell. 1993;72(6):971–83.

    Google Scholar 

  2. Langbehn DR, Brinkman RR, Falush D, Paulsen JS, Hayden MR. A new model for prediction of the age of onset and penetrance for Huntington’s disease based on CAG length. Clin Genet. 2004;65(4):267–77.

    Article  PubMed  CAS  Google Scholar 

  3. Hoppitt T, Calvert M, Pall H, Rickards H, Sackley C. Huntington’s disease. Lancet. 2010;376(9751):1463–4.

    Article  PubMed  CAS  Google Scholar 

  4. Ross CA, Tabrizi SJ. Huntington’s disease: from molecular pathogenesis to clinical treatment. Lancet Neurol. 2011;10(1):83–98.

    Article  PubMed  CAS  Google Scholar 

  5. Wexler NS, Lorimer J, Porter J, Gomez F, Moskowitz C, Shackell E, et al. Venezuelan kindreds reveal that genetic and environmental factors modulate Huntington’s disease age of onset. Proc Natl Acad Sci USA. 2004;101(10):3498–503.

    Article  PubMed  CAS  Google Scholar 

  6. Browne SE. Mitochondria and Huntington’s disease pathogenesis: insight from genetic and chemical models. Ann N Y Acad Sci. 2008;1147:358–82.

    Article  PubMed  CAS  Google Scholar 

  7. Gu M, Gash MT, Mann VM, Javoy-Agid F, Cooper JM, Schapira AH. Mitochondrial defect in Huntington’s disease caudate nucleus. Ann Neurol. 1996;39(3):385–9.

    Article  PubMed  CAS  Google Scholar 

  8. Mann VM, Cooper JM, Javoy-Agid F, Agid Y, Jenner P, Schapira AH. Mitochondrial function and parental sex effect in Huntington’s disease. Lancet. 1990;336(8717):749.

    Article  PubMed  CAS  Google Scholar 

  9. Napoli E, Wong S, Hung C, Ross-Inta C, Bomdica P, Giulivi C. Defective mitochondrial disulfide relay system, altered mitochondrial morphology and function in Huntington’s disease. Hum Mol Genet. 2013;22(5):989–1004.

    Article  PubMed  CAS  Google Scholar 

  10. Imarisio S, Carmichael J, Korolchuk V, Chen CW, Saiki S, Rose C, et al. Huntington’s disease: from pathology and genetics to potential therapies. Biochem J. 2008;412(2):191–209.

    Article  PubMed  CAS  Google Scholar 

  11. Weydt P, Pineda VV, Torrence AE, Libby RT, Satterfield TF, Lazarowski ER, et al. Thermoregulatory and metabolic defects in Huntington’s disease transgenic mice implicate PGC-1alpha in Huntington’s disease neurodegeneration. Cell Metab. 2006;4(5):349–62.

    Article  PubMed  CAS  Google Scholar 

  12. Cui L, Jeong H, Borovecki F, Parkhurst CN, Tanese N, Krainc D. Transcriptional repression of PGC-1alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration. Cell. 2006;127(1):59–69.

    Article  PubMed  CAS  Google Scholar 

  13. Turner C, Schapira AH. Mitochondrial matters of the brain: the role in Huntington’s disease. J Bioenerg Biomembr. 2010;42(3):193–8.

    Article  PubMed  CAS  Google Scholar 

  14. Oliveira JM. Mitochondrial bioenergetics and dynamics in Huntington’s disease: tripartite synapses and selective striatal degeneration. J Bioenerg Biomembr. 2010;42(3):227–34.

    Article  PubMed  CAS  Google Scholar 

  15. Quintanilla RA, Johnson GV. Role of mitochondrial dysfunction in the pathogenesis of Huntington’s disease. Brain Res Bull. 2009;80(4–5):242–7.

    Article  PubMed  CAS  Google Scholar 

  16. Beal MF. Mitochondria and neurodegeneration. Novartis Found Symp. 2007;287:183–92 (discussion 92–6).

  17. Mochel F, Haller RG. Energy deficit in Huntington disease: why it matters. J Clin Invest. 2011;121(2):493–9.

    Article  PubMed  CAS  Google Scholar 

  18. Rosenstock TR, Duarte AI. Rego AC. Curr Drug Targets: Mitochondrial-associated metabolic changes and neurodegeneration in Huntington’s disease—from clinical features to the bench; 2010.

    Google Scholar 

  19. Browne SE, Beal MF. Oxidative damage in Huntington’s disease pathogenesis. Antioxid Redox Signal. 2006;8(11–12):2061–73.

    Article  PubMed  CAS  Google Scholar 

  20. Chen HI, Liou SH, Ho SF, Wu KY, Sun CW, Chen MF, et al. Oxidative DNA damage estimated by plasma 8-hydroxydeoxyguanosine (8-OHdG): influence of 4,4′-methylenebis (2-chloroaniline) exposure and smoking. J Occup Health. 2007;49(5):389–98.

    Article  PubMed  CAS  Google Scholar 

  21. Sorolla MA, Reverter-Branchat G, Tamarit J, Ferrer I, Ros J, Cabiscol E. Proteomic and oxidative stress analysis in human brain samples of Huntington disease. Free Radic Biol Med. 2008;45(5):667–78.

    Article  PubMed  CAS  Google Scholar 

  22. Santamaria A, Perez-Severiano F, Rodriguez-Martinez E, Maldonado PD, Pedraza-Chaverri J, Rios C, et al. Comparative analysis of superoxide dismutase activity between acute pharmacological models and a transgenic mouse model of Huntington’s disease. Neurochem Res. 2001;26(4):419–24.

    Article  PubMed  CAS  Google Scholar 

  23. Nisoli E, Tonello C, Cardile A, Cozzi V, Bracale R, Tedesco L, et al. Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS. Science. 2005;310(5746):314–7.

    Article  PubMed  CAS  Google Scholar 

  24. Haigis MC, Guarente LP. Mammalian sirtuins–emerging roles in physiology, aging, and calorie restriction. Genes Dev. 2006;20(21):2913–21.

    Article  PubMed  CAS  Google Scholar 

  25. Chalkiadaki A, Guarente L. Sirtuins mediate mammalian metabolic responses to nutrient availability. Nat Rev Endocrinol. 2012;8(5):287–96.

    Article  PubMed  CAS  Google Scholar 

  26. Shimokawa I, Trindade LS. Dietary restriction and aging in rodents: a current view on its molecular mechanisms. Aging Dis. 2010;1(2):89–107.

    PubMed  Google Scholar 

  27. Canto C, Auwerx J. Caloric restriction, SIRT1 and longevity. Trends Endocrinol Metab. 2009;20(7):325–31.

    Article  PubMed  CAS  Google Scholar 

  28. Wakeling LA, Ions LJ, Ford D. Could Sirt1-mediated epigenetic effects contribute to the longevity response to dietary restriction and be mimicked by other dietary interventions? Age (Dordr). 2009;31(4):327–41.

    Article  CAS  Google Scholar 

  29. Maiese K, Chong ZZ, Shang YC. OutFOXOing disease and disability: the therapeutic potential of targeting FoxO proteins. Trends Mol Med. 2008;14(5):219–27.

    Article  PubMed  CAS  Google Scholar 

  30. Hasegawa K, Wakino S, Yoshioka K, Tatematsu S, Hara Y, Minakuchi H, et al. Sirt1 protects against oxidative stress-induced renal tubular cell apoptosis by the bidirectional regulation of catalase expression. Biochem Biophys Res Commun. 2008;372(1):51–6.

    Article  PubMed  CAS  Google Scholar 

  31. Chong ZZ, Maiese K. Enhanced tolerance against early and late apoptotic oxidative stress in mammalian neurons through nicotinamidase and sirtuin mediated pathways. Curr Neurovasc Res. 2008;5(3):159–70.

    Article  PubMed  CAS  Google Scholar 

  32. Tanno M, Kuno A, Yano T, Miura T, Hisahara S, Ishikawa S, et al. Induction of manganese superoxide dismutase by nuclear translocation and activation of SIRT1 promotes cell survival in chronic heart failure. J Biol Chem. 2010;285(11):8375–82.

    Article  PubMed  CAS  Google Scholar 

  33. Tsunemi T, Ashe TD, Morrison BE, Soriano KR, Au J, Roque RA, et al. PGC-1alpha rescues Huntington’s disease proteotoxicity by preventing oxidative stress and promoting TFEB function. Sci Transl Med. 2012;4(142):142ra97.

    Google Scholar 

  34. La Spada AR. PPARGC1A/PGC-1alpha, TFEB and enhanced proteostasis in Huntington disease: defining regulatory linkages between energy production and protein-organelle quality control. Autophagy. 2012;8(12):1845–7.

    Article  PubMed  Google Scholar 

  35. Ramadori G, Lee CE, Bookout AL, Lee S, Williams KW, Anderson J, et al. Brain SIRT1: anatomical distribution and regulation by energy availability. J Neurosci. 2008;28(40):9989–96.

    Article  PubMed  CAS  Google Scholar 

  36. Rine J, Herskowitz I. Four genes responsible for a position effect on expression from HML and HMR in Saccharomyces cerevisiae. Genetics. 1987;116(1):9–22.

    PubMed  CAS  Google Scholar 

  37. Guarente L. Sirtuins, aging, and metabolism. Cold Spring Harb Symp Quant Biol. 2011;76:81–90.

    Article  PubMed  CAS  Google Scholar 

  38. Guarente L, Franklin H. Epstein lecture: sirtuins, aging, and medicine. N Engl J Med. 2011;364(23):2235–44.

    Article  PubMed  CAS  Google Scholar 

  39. Nakagawa T, Guarente L. Sirtuins at a glance. J Cell Sci. 2011;124(Pt 6):833–8.

    Article  PubMed  CAS  Google Scholar 

  40. Tanno M, Sakamoto J, Miura T, Shimamoto K, Horio Y. Nucleocytoplasmic shuttling of the NAD+-dependent histone deacetylase SIRT1. J Biol Chem. 2007;282(9):6823–32.

    Article  PubMed  CAS  Google Scholar 

  41. Haigis MC, Sinclair DA. Mammalian sirtuins: biological insights and disease relevance. Annu Rev Pathol. 2010;5:253–95.

    Article  PubMed  CAS  Google Scholar 

  42. Araki T, Sasaki Y, Milbrandt J. Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration. Science. 2004;305(5686):1010–3.

    Article  PubMed  CAS  Google Scholar 

  43. Srivastava S, Haigis MC. Role of sirtuins and calorie restriction in neuroprotection: implications in Alzheimer’s and Parkinson’s diseases. Curr Pharm Des. 2011;17(31):3418–33.

    Article  PubMed  CAS  Google Scholar 

  44. Donmez G, Wang D, Cohen DE, Guarente L. SIRT1 suppresses beta-amyloid production by activating the alpha-secretase gene ADAM10. Cell. 2010;142(2):320–32.

    Article  PubMed  CAS  Google Scholar 

  45. Polito L, Kehoe PG, Forloni G, Albani D. The molecular genetics of sirtuins: association with human longevity and age-related diseases. Int J Mol Epidemiol Genet. 2010;1(3):214–25.

    PubMed  CAS  Google Scholar 

  46. Wang J, Fivecoat H, Ho L, Pan Y, Ling E, Pasinetti GM. The role of Sirt1: at the crossroad between promotion of longevity and protection against Alzheimer’s disease neuropathology. Biochim Biophys Acta. 2010;1804(8):1690–4.

    Article  PubMed  CAS  Google Scholar 

  47. Kim D, Nguyen MD, Dobbin MM, Fischer A, Sananbenesi F, Rodgers JT, et al. SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer’s disease and amyotrophic lateral sclerosis. EMBO J. 2007;26(13):3169–79.

    Article  PubMed  CAS  Google Scholar 

  48. Donmez G, Arun A, Chung CY, McLean PJ, Lindquist S, Guarente L. SIRT1 protects against alpha-synuclein aggregation by activating molecular chaperones. J Neurosci. 2012;32(1):124–32.

    Article  PubMed  CAS  Google Scholar 

  49. Jiang M, Wang J, Fu J, Du L, Jeong H, West T, et al. Neuroprotective role of Sirt1 in mammalian models of Huntington’s disease through activation of multiple Sirt1 targets. Nat Med. 2012;18(1):153–8.

    Article  CAS  Google Scholar 

  50. Jeong H, Cohen DE, Cui L, Supinski A, Savas JN, Mazzulli JR, et al. Sirt1 mediates neuroprotection from mutant huntingtin by activation of the TORC1 and CREB transcriptional pathway. Nat Med. 2012;18(1):159–65.

    Article  CAS  Google Scholar 

  51. Parker JA, Arango M, Abderrahmane S, Lambert E, Tourette C, Catoire H, et al. Resveratrol rescues mutant polyglutamine cytotoxicity in nematode and mammalian neurons. Nat Genet. 2005;37(4):349–50.

    Article  PubMed  CAS  Google Scholar 

  52. Pallos J, Bodai L, Lukacsovich T, Purcell JM, Steffan JS, Thompson LM, et al. Inhibition of specific HDACs and sirtuins suppresses pathogenesis in a Drosophila model of Huntington’s disease. Hum Mol Genet. 2008;17(23):3767–75.

    Article  PubMed  CAS  Google Scholar 

  53. Burnett C, Valentini S, Cabreiro F, Goss M, Somogyvari M, Piper MD, et al. Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila. Nature. 2011;477(7365):482–5.

    Article  PubMed  CAS  Google Scholar 

  54. Jiang M, Wang J, Fu J, Du L, Jeong H, West T, et al. Neuroprotective role of Sirt1 in mammalian models of Huntington’s disease through activation of multiple Sirt1 targets. Nat Med. 2012;18(1):153–8.

    Article  CAS  Google Scholar 

  55. Jeong H, Cohen DE, Cui L, Supinski A, Savas JN, Mazzulli JR, et al. Sirt1 mediates neuroprotection from mutant huntingtin by activation of the TORC1 and CREB transcriptional pathway. Nat Med. 2011;18(1):159–65.

    Article  PubMed  Google Scholar 

  56. Zuccato C, Liber D, Ramos C, Tarditi A, Rigamonti D, Tartari M, et al. Progressive loss of BDNF in a mouse model of Huntington’s disease and rescue by BDNF delivery. Pharmacol Res. 2005;52(2):133–9.

    Article  PubMed  CAS  Google Scholar 

  57. Zuccato C, Ciammola A, Rigamonti D, Leavitt BR, Goffredo D, Conti L, et al. Loss of huntingtin-mediated BDNF gene transcription in Huntington’s disease. Science. 2001;293(5529):493–8.

    Article  PubMed  CAS  Google Scholar 

  58. Zuccato C, Cattaneo E. Role of brain-derived neurotrophic factor in Huntington’s disease. Prog Neurobiol. 2007;81(5–6):294–330.

    Article  PubMed  CAS  Google Scholar 

  59. Xie Y, Hayden MR, Xu B. BDNF overexpression in the forebrain rescues Huntington’s disease phenotypes in YAC128 mice. J Neurosci. 2010;30(44):14708–18.

    Article  PubMed  CAS  Google Scholar 

  60. Giralt A, Carreton O, Lao-Peregrin C, Martin ED, Alberch J. Conditional BDNF release under pathological conditions improves Huntington’s disease pathology by delaying neuronal dysfunction. Mol Neurodegener. 2011;6(1):71.

    Article  PubMed  CAS  Google Scholar 

  61. Duan W, Guo Z, Jiang H, Ware M, Li XJ, Mattson MP. Dietary restriction normalizes glucose metabolism and BDNF levels, slows disease progression, and increases survival in huntingtin mutant mice. Proc Natl Acad Sci USA. 2003;100(5):2911–6.

    Article  PubMed  CAS  Google Scholar 

  62. Duan W, Peng Q, Masuda N, Ford E, Tryggestad E, Ladenheim B, et al. Sertraline slows disease progression and increases neurogenesis in N171-82Q mouse model of Huntington’s disease. Neurobiol Dis. 2008;30(3):312–22.

    Article  PubMed  CAS  Google Scholar 

  63. Peng Q, Masuda N, Jiang M, Li Q, Zhao M, Ross CA, et al. The antidepressant sertraline improves the phenotype, promotes neurogenesis and increases BDNF levels in the R6/2 Huntington’s disease mouse model. Exp Neurol. 2008;210(1):154–63.

    Article  PubMed  CAS  Google Scholar 

  64. Duan W, Guo Z, Jiang H, Ware M, Mattson MP. Reversal of behavioral and metabolic abnormalities, and insulin resistance syndrome, by dietary restriction in mice deficient in brain-derived neurotrophic factor. Endocrinology. 2003;144(6):2446–53.

    Article  PubMed  CAS  Google Scholar 

  65. Cohen E, Dillin A. The insulin paradox: aging, proteotoxicity and neurodegeneration. Nat Rev Neurosci. 2008;9(10):759–67.

    Article  PubMed  CAS  Google Scholar 

  66. Wang B, Goode J, Best J, Meltzer J, Schilman PE, Chen J, et al. The insulin-regulated CREB coactivator TORC promotes stress resistance in Drosophila. Cell Metab. 2008;7(5):434–44.

    Article  PubMed  CAS  Google Scholar 

  67. Silverman N, Maniatis T. NF-kappaB signaling pathways in mammalian and insect innate immunity. Genes Dev. 2001;15(18):2321–42.

    Article  PubMed  CAS  Google Scholar 

  68. Ho DJ, Calingasan NY, Wille E, Dumont M, Beal MF. Resveratrol protects against peripheral deficits in a mouse model of Huntington’s disease. Exp Neurol. 2010;225(1):74–84.

    Article  PubMed  CAS  Google Scholar 

  69. Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 2006;444(7117):337–42.

    Article  PubMed  CAS  Google Scholar 

  70. Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov. 2006;5(6):493–506.

    Article  PubMed  CAS  Google Scholar 

  71. Kumar P, Padi SS, Naidu PS, Kumar A. Effect of resveratrol on 3-nitropropionic acid-induced biochemical and behavioural changes: possible neuroprotective mechanisms. Behav Pharmacol. 2006;17(5–6):485–92.

    Article  PubMed  CAS  Google Scholar 

  72. Maher P, Dargusch R, Bodai L, Gerard PE, Purcell JM, Marsh JL. ERK activation by the polyphenols fisetin and resveratrol provides neuroprotection in multiple models of Huntington’s disease. Hum Mol Genet. 2011;20(2):261–70.

    Article  PubMed  CAS  Google Scholar 

  73. Scott E, Steward WP, Gescher AJ, Brown K. Resveratrol in human cancer chemoprevention–choosing the ‘right’ dose. Mol Nutr Food Res. 2012;56(1):7–13.

    Article  PubMed  CAS  Google Scholar 

  74. Stocco B, Toledo K, Salvador M, Paulo M, Koyama N, Torqueti Toloi MR. Dose-dependent effect of resveratrol on bladder cancer cells: chemoprevention and oxidative stress. Maturitas. 2012;72(1):72–8.

    Article  PubMed  CAS  Google Scholar 

  75. Price NL, Gomes AP, Ling AJ, Duarte FV, Martin-Montalvo A, North BJ, et al. SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function. Cell Metab. 2012;15(5):675–90.

    Article  PubMed  CAS  Google Scholar 

  76. Girbovan C, Morin L, Plamondon H. Repeated resveratrol administration confers lasting protection against neuronal damage but induces dose-related alterations of behavioral impairments after global ischemia. Behav Pharmacol. 2012;23(1):1–13.

    Article  PubMed  CAS  Google Scholar 

  77. Milne JC, Lambert PD, Schenk S, Carney DP, Smith JJ, Gagne DJ, et al. Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature. 2007;450(7170):712–6.

    Article  PubMed  CAS  Google Scholar 

  78. Pacholec M, Bleasdale JE, Chrunyk B, Cunningham D, Flynn D, Garofalo RS, et al. SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1. J Biol Chem. 2010;285(11):8340–51.

    Article  PubMed  CAS  Google Scholar 

  79. Hathorn T, Snyder-Keller A, Messer A. Nicotinamide improves motor deficits and upregulates PGC-1alpha and BDNF gene expression in a mouse model of Huntington’s disease. Neurobiol Dis. 2011;41(1):43–50.

    Article  PubMed  CAS  Google Scholar 

  80. Kazantsev AG, Thompson LM. Therapeutic application of histone deacetylase inhibitors for central nervous system disorders. Nat Rev Drug Discov. 2008;7(10):854–68.

    Article  PubMed  CAS  Google Scholar 

  81. Grozinger CM, Chao ED, Blackwell HE, Moazed D, Schreiber SL. Identification of a class of small molecule inhibitors of the sirtuin family of NAD-dependent deacetylases by phenotypic screening. J Biol Chem. 2001;276(42):38837–43.

    Article  PubMed  CAS  Google Scholar 

  82. Mai A, Massa S, Lavu S, Pezzi R, Simeoni S, Ragno R, et al. Design, synthesis, and biological evaluation of sirtinol analogues as class III histone/protein deacetylase (Sirtuin) inhibitors. J Med Chem. 2005;48(24):7789–95.

    Article  PubMed  CAS  Google Scholar 

  83. Napper AD, Hixon J, McDonagh T, Keavey K, Pons JF, Barker J, et al. Discovery of indoles as potent and selective inhibitors of the deacetylase SIRT1. J Med Chem. 2005;48(25):8045–54.

    Article  PubMed  CAS  Google Scholar 

  84. Trapp J, Meier R, Hongwiset D, Kassack MU, Sippl W, Jung M. Structure-activity studies on suramin analogues as inhibitors of NAD+-dependent histone deacetylases (sirtuins). ChemMedChem. 2007;2(10):1419–31.

    Article  PubMed  CAS  Google Scholar 

  85. Chopra V, Quinti L, Kim J, Vollor L, Narayanan KL, Edgerly C, et al. The sirtuin 2 inhibitor AK-7 is neuroprotective in Huntington’s disease mouse models. Cell Rep. 2012;2(6):1492–7.

    Article  PubMed  CAS  Google Scholar 

  86. Zhang F, Wang S, Gan L, Vosler PS, Gao Y, Zigmond MJ, et al. Protective effects and mechanisms of sirtuins in the nervous system. Prog Neurobiol. 2011;95(3):373–95.

    Article  PubMed  CAS  Google Scholar 

  87. Donmez G, Outeiro TF. SIRT1 and SIRT2: emerging targets in neurodegeneration. EMBO Mol Med. 2013;5(3):344–52.

    Google Scholar 

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Acknowledgments

The author acknowledges grants NS074196 and NS072344 from the National Institutes of Health, CHDI A3875, Hereditary Disease Foundation, which supported preparation of this manuscript and some of the research reported herein. The author declares no conflicts of interest in writing this article.

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  1. Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, CMSC 8-121, 600 North Wolfe Street, Baltimore, MD, 21287, USA

    Wenzhen Duan

  2. Department of Neuroscience, Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Wenzhen Duan

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Duan, W. Targeting Sirtuin-1 in Huntington’s Disease: Rationale and Current Status. CNS Drugs 27, 345–352 (2013). https://doi.org/10.1007/s40263-013-0055-0

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