Neurotherapeutics

, Volume 10, Issue 4, pp 709–721 | Cite as

Epigenetics of Alzheimer’s Disease and Frontotemporal Dementia

  • Chendhore S. Veerappan
  • Sama Sleiman
  • Giovanni Coppola
Review

Abstract

This article will review the recent advances in the understanding of the role of epigenetic modifications and the promise of future epigenetic therapy in neurodegenerative dementias, including Alzheimer’s disease and frontotemporal dementia.

Keywords

Neurodegeneration Epigenetics Alzheimer’s disease Frontotemporal dementia Epigenetic drugs Therapy 

Supplementary material

13311_2013_219_MOESM1_ESM.pdf (1.2 mb)
ESM 1(PDF 1.19 MB)

References

  1. 1.
    McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 2011;7:263–269.PubMedGoogle Scholar
  2. 2.
    Ratnavalli E, Brayne C, Dawson K, Hodges JR. The prevalence of frontotemporal dementia. Neurology 2002;58:1615–1621.PubMedGoogle Scholar
  3. 3.
    Rocca WA, Petersen RC, Knopman DS, et al. Trends in the incidence and prevalence of Alzheimer’s disease, dementia, and cognitive impairment in the United States. Alzheimers Dement 2011;7:80–93.PubMedGoogle Scholar
  4. 4.
    Mangialasche F, Solomon A, Winblad B, Mecocci P, Kivipelto M. Alzheimer’s disease: clinical trials and drug development. Lancet Neurol 2010;9:702–716.PubMedGoogle Scholar
  5. 5.
    Boxer AL, Gold M, Huey E, et al. Frontotemporal degeneration, the next therapeutic frontier: Molecules and animal models for frontotemporal degeneration drug development. Alzheimers Dement 2012;9:188–176.Google Scholar
  6. 6.
    Klucken J, McLean PJ, Gomez-Tortosa E, Ingelsson M, Hyman BT. Neuritic alterations and neural system dysfunction in Alzheimer’s disease and dementia with Lewy bodies. Neurochem Res 2003;28:1683–1691.PubMedGoogle Scholar
  7. 7.
    Vassar R. BACE1: the beta-secretase enzyme in Alzheimer’s disease. J Mol Neurosci 2004;23:105–114.PubMedGoogle Scholar
  8. 8.
    Xia W. Role of presenilin in gamma-secretase cleavage of amyloid precursor protein. Exp Gerontol 2000;35:453–460.PubMedGoogle Scholar
  9. 9.
    Bentahir M, Nyabi O, Verhamme J, et al. Presenilin clinical mutations can affect gamma-secretase activity by different mechanisms. J Neurochem 2006;96:732–742.PubMedGoogle Scholar
  10. 10.
    Findeis MA. The role of amyloid beta peptide 42 in Alzheimer’s disease. Pharmacol Ther 2007;116:266–286.PubMedGoogle Scholar
  11. 11.
    Niemitz E. TREM2 and Alzheimer’s disease. Nat Genet 2012;45:11–11.Google Scholar
  12. 12.
    Van Der Flier WM, Pijnenburg YA, Fox NC, Scheltens P. Early-onset versus late-onset Alzheimer’s disease: the case of the missing APOE epsilon 4 allele. Lancet 2011;10:280–288Google Scholar
  13. 13.
    Campion D, Dumanchin C, Hannequin D, et al. Early-onset autosomal dominant Alzheimer disease: prevalence, genetic heterogeneity, and mutation spectrum. Am J Hum Genet 1999;65:664–670.PubMedGoogle Scholar
  14. 14.
    Lambert J-C, Amouyel P. Genetic heterogeneity of Alzheimer’s disease: complexity and advances. Psychoneuroendocrinology 2007;32(Suppl. 1):S62-70.PubMedGoogle Scholar
  15. 15.
    Mayeux R, Stern Y, Spanton S. Heterogeneity in dementia of the Alzheimer type: Evidence of subgroups. Neurology 1985;35:453–453.PubMedGoogle Scholar
  16. 16.
    Gold G, Blouin J-L, Herrmann FR, et al. Specific BACE1 genotypes provide additional risk for late-onset Alzheimer disease in APOE epsilon 4 carriers. Am J Med Genet B Neuropsychiatr Genet 2003;119B:44–47.PubMedGoogle Scholar
  17. 17.
    Gorno-Tempini ML, Hillis AE, Weintraub S, et al. Classification of primary progressive aphasia and its variants. Neurology 2011;76:1006–1014.PubMedGoogle Scholar
  18. 18.
    Seelaar H, Rohrer JD, Pijnenburg YAL, Fox NC, Van Swieten JC. Clinical, genetic and pathological heterogeneity of frontotemporal dementia: a review. J Neurol Neurosurg Psychiatry 2011;82:476–486.PubMedGoogle Scholar
  19. 19.
    Majounie E, Renton AE, Mok K, et al. Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study. Lancet Neurol 2012;11:323–330.PubMedGoogle Scholar
  20. 20.
    Urwin H, Ghazi-Noori S, Collinge J, Isaacs A. The role of CHMP2B in frontotemporal dementia. Biochem Soc Trans 2009;37:208–212.PubMedGoogle Scholar
  21. 21.
    Isaacs AM, Johannsen P, Holm I, Nielsen JE. Frontotemporal dementia caused by CHMP2B mutations. Curr Alzheimer Res 2011;8:246–251.PubMedGoogle Scholar
  22. 22.
    Bettens K, Sleegers K, Van Broeckhoven C. Genetic insights in Alzheimer’s disease. Lancet Neurol 2013;12:92–104.PubMedGoogle Scholar
  23. 23.
    Rademakers R, Mackenzie IRA. Recent advances in the molecular basis of frontotemporal dementia. Nat Rev Neurol 2013;8:423–434.Google Scholar
  24. 24.
    Ambegaokar SS, Jackson GR. Functional genomic screen and network analysis reveal novel modifiers of tauopathy dissociated from tau phosphorylation. Hum Mol Genet 2011;20:4947–4977.PubMedGoogle Scholar
  25. 25.
    Dupont C, Armant DR, Brenner CA. Epigenetics: definition, mechanisms and clinical perspective. Semin Reprod Med 2009;27:351–357.PubMedGoogle Scholar
  26. 26.
    Griffith JS, Mahler HR. DNA Ticketing theory of memory. Nature 1969;223:580–582.PubMedGoogle Scholar
  27. 27.
    Kouzarides T. Chromatin modifications and their function. Cell 2007;128:693–705.PubMedGoogle Scholar
  28. 28.
    Strahl BD, Allis CD. The language of covalent histone modifications. Nature 2000;403:41–45.PubMedGoogle Scholar
  29. 29.
    Rando OJ. Combinatorial complexity in chromatin structure and function: revisiting the histone code. Curr Opin Genet Develop 2012;22:148–155.Google Scholar
  30. 30.
    Tweedie-Cullen RY, Brunner AM, Grossmann J, et al. Identification of combinatorial patterns of post-translational modifications on individual histones in the mouse brain. PloS One 2012;7:e36980.PubMedGoogle Scholar
  31. 31.
    Costa FF. Non-coding RNAs, epigenetics and complexity. Gene 2008;410:9–17.PubMedGoogle Scholar
  32. 32.
    Champagne FA. Epigenetics and developmental plasticity across species. Develop Psychobiol 2013;55:33–41.Google Scholar
  33. 33.
    Jones PA, Laird PW. Cancer epigenetics comes of age. Nat Genet 1999;21:163–167.PubMedGoogle Scholar
  34. 34.
    Rodenhiser D, Mann M. Epigenetics and human disease: translating basic biology into clinical applications. CMAJ 2006;174:341–348.PubMedGoogle Scholar
  35. 35.
    Liu L, Van Groen T, Kadish I, Tollefsbol TO. DNA methylation impacts on learning and memory in aging. Neurobiol Aging 2009;30:549–560.PubMedGoogle Scholar
  36. 36.
    Peleg S, Sananbenesi F, Zovoilis A, et al. (2010). Altered histone acetylation is associated with age-dependent memory impairment in mice. Science 328:753–756.PubMedGoogle Scholar
  37. 37.
    Rando TA. Epigenetics and aging. Exp Gerontol 2010;45:253–254.PubMedGoogle Scholar
  38. 38.
    Alarcón JM, Malleret G, Touzani K, et al. Chromatin acetylation, memory, and LTP are impaired in CBP+/− mice: a model for the cognitive deficit in Rubinstein-Taybi syndrome and its amelioration. Neuron 2004;42:947–959.PubMedGoogle Scholar
  39. 39.
    Jiang Y, Langley B, Lubin FD, et al. Epigenetics in the nervous system. J Neurosci 2008;28:11753–11759.PubMedGoogle Scholar
  40. 40.
    Levenson JM, Sweatt JD. Epigenetic mechanisms in memory formation. Nat Rev Neurosci 2005;6:108–118.PubMedGoogle Scholar
  41. 41.
    Hsieh J, Gage FH. Chromatin remodeling in neural development and plasticity. Curr Opin Cell Biol 2005;17:664–671.PubMedGoogle Scholar
  42. 42.
    Hirabayashi Y, Gotoh Y. Epigenetic control of neural precursor cell fate during development. Nat Rev Neurosci 2010;11:377–388.PubMedGoogle Scholar
  43. 43.
    Numata S, Ye T, Hyde TM, et al. DNA methylation signatures in development and aging of the human prefrontal cortex. Am J Hum Genet 2012;90:260–272.PubMedGoogle Scholar
  44. 44.
    Siegmund KD, Connor CM, Campan M, et al. DNA methylation in the human cerebral cortex is dynamically regulated throughout the life span and involves differentiated neurons. PloS One 2007;2:e895.PubMedGoogle Scholar
  45. 45.
    Szulwach KE, Li X, Li Y, et al. 5-hmC-mediated epigenetic dynamics during postnatal neurodevelopment and aging. Nat Neurosci 2011;14:1607–1616.PubMedGoogle Scholar
  46. 46.
    Peter CJ, Akbarian S. Balancing histone methylation activities in psychiatric disorders. Trends Mol Med 2011;17:372–379.PubMedGoogle Scholar
  47. 47.
    Tsankova N, Renthal W, Kumar A, Nestler EJ. Epigenetic regulation in psychiatric disorders. Nat Rev Neurosci 2007;8:355–367.PubMedGoogle Scholar
  48. 48.
    Clayton-Smith J, Watson P, Ramsden S, Black G. Somatic mutation in MECP2 as a non-fatal neurodevelopmental disorder in males. Lancet 2000;356:830–832.PubMedGoogle Scholar
  49. 49.
    Meloni I, Bruttini M, Longo I, et al. A mutation in the rett syndrome gene, MECP2, causes X-linked mental retardation and progressive spasticity in males. Am J Hum Genet 2000;67:982–985.PubMedGoogle Scholar
  50. 50.
    Klein CJ, Botuyan M-V, Wu Y, et al. Mutations in DNMT1 cause hereditary sensory neuropathy with dementia and hearing loss. Nat Genet 2011;43: 595–600.PubMedGoogle Scholar
  51. 51.
    De Greef JC, Wang J, Balog J, et al. Mutations in ZBTB24 are associated with immunodeficiency, centromeric instability, and facial anomalies syndrome type 2. Am J Hum Genet 2011;88:796–804.PubMedGoogle Scholar
  52. 52.
    Xu GL, Bestor TH, Bourc’his D, et al. Chromosome instability and immunodeficiency syndrome caused by mutations in a DNA methyltransferase gene. Nature 1999;402:187–191.PubMedGoogle Scholar
  53. 53.
    Covington HE, Maze I, Sun H, et al. A role for repressive histone methylation in cocaine-induced vulnerability to stress. Neuron 2011;71:656–670.PubMedGoogle Scholar
  54. 54.
    Lim DA, Huang Y-C, Swigut T, et al. Chromatin remodelling factor Mll1 is essential for neurogenesis from postnatal neural stem cells. Nature 2009;458:529–533.PubMedGoogle Scholar
  55. 55.
    Pereira JD, Sansom SN, Smith J, Dobenecker M-W, Tarakhovsky A, Livesey FJ. Ezh2, the histone methyltransferase of PRC2, regulates the balance between self-renewal and differentiation in the cerebral cortex. Proc Natl Acad Sci U S A 2010;107:15957–15962.PubMedGoogle Scholar
  56. 56.
    Adegbola A, Gao H, Sommer S, Browning M. A novel mutation in JARID1C/SMCX in a patient with autism spectrum disorder (ASD). Am J Med Genet A 2008;146A:505–511.PubMedGoogle Scholar
  57. 57.
    Burgold T, Spreafico F, De Santa F, et al. The histone H3 lysine 27-specific demethylase Jmjd3 is required for neural commitment. PloS One 2008;3:e3034.PubMedGoogle Scholar
  58. 58.
    Tahiliani M, Mei P, Fang R, et al. The histone H3K4 demethylase SMCX links REST target genes to X-linked mental retardation. Nature 2007;447:601–605.PubMedGoogle Scholar
  59. 59.
    Gräff J, Tsai L-H. Histone acetylation: molecular mnemonics on the chromatin. Nat Rev Neurosci 2013;14:97–111.PubMedGoogle Scholar
  60. 60.
    Qureshi IA, Mehler MF. Emerging roles of non-coding RNAs in brain evolution, development, plasticity and disease. Nat Rev Neurosci 2012;13:528–541.PubMedGoogle Scholar
  61. 61.
    Niland CN, Merry CR, Khalil AM. Emerging roles forlong non-coding RNAs in cancer and neurological disorders. Front Genet 2012;3:25.PubMedGoogle Scholar
  62. 62.
    Mercer TR, Dinger ME, Sunkin SM, Mehler MF, Mattick JS. Specific expression of long noncoding RNAs in the mouse brain. Proc Natl Acad Sci U S A 2008;105:716–721.PubMedGoogle Scholar
  63. 63.
    Spadaro PA, Bredy TW. Emerging role of non-coding RNA in neural plasticity, cognitive function, and neuropsychiatric disorders. Front Genet 2012;3:132.PubMedGoogle Scholar
  64. 64.
    Ng S-Y, Lin L, Soh BS, Stanton LW. Long noncoding RNAs in development and disease of the central nervous system. Trends Genet 2013;29:461–468.PubMedGoogle Scholar
  65. 65.
    Telese F, Gamliel A, Skowronska-Krawczyk D, Garcia-Bassets I, Rosenfeld MG. “Seq-ing” insights into the epigenetics of neuronal gene regulation. Neuron 2013;77:606–623.PubMedGoogle Scholar
  66. 66.
    Tushir JS, Akbarian S. Chromatin-bound RNA and the neurobiology of psychiatric disease. Neuroscience 2013 Jul 3 [Epub ahead of print].Google Scholar
  67. 67.
    Chan TA. Epigenetic therapy: use of agents targeting deacetylation and methylation in cancer management. Onco Targets Ther 2013;6:223–232.PubMedGoogle Scholar
  68. 68.
    Mack GS. To selectivity and beyond. Nat Biotechnol 2010;28:1259–1266.PubMedGoogle Scholar
  69. 69.
    Barrachina M, Ferrer I. DNA methylation of Alzheimer disease and tauopathy-related genes in postmortem brain. J Neuropathol Exp Neurol 2009;68:880–891.PubMedGoogle Scholar
  70. 70.
    Brohede J, Rinde M, Winblad B, Graff C. A DNA methylation study of the amyloid precursor protein gene in several brain regions from patients with familial Alzheimer disease. J Neurogenet 2010;24:179–181.PubMedGoogle Scholar
  71. 71.
    Bakulski KM, Dolinoy DC, Sartor MA, et al. Genome-wide DNA methylation differences between late-onset Alzheimer’s disease and cognitively normal controls in human frontal cortex. J Alzheimers Dis 2012;29:571–588.PubMedGoogle Scholar
  72. 72.
    Bollati V, Galimberti D, Pergoli L, et al. DNA methylation in repetitive elements and Alzheimer disease. Brain Behav Immun 2011;25:1078–1083.PubMedGoogle Scholar
  73. 73.
    Iwata N, Tsubuki S, Takaki Y, et al. Metabolic regulation of brain Abeta by neprilysin. Science 2001;292:1550–1552.PubMedGoogle Scholar
  74. 74.
    Chen K-L, Wang SS-S, Yang Y-Y, Yuan R-Y, Chen R-M, Hu C-J. The epigenetic effects of amyloid-beta(1–40) on global DNA and neprilysin genes in murine cerebral endothelial cells. Biochem Biophys Res Commun 2009;378:57–61.PubMedGoogle Scholar
  75. 75.
    Galimberti D, D’Addario C, Dell’osso B, et al. Progranulin gene (GRN) promoter methylation is increased in patients with sporadic frontotemporal lobar degeneration. Neurol Sci 2013;34:899–903.PubMedGoogle Scholar
  76. 76.
    Xi Z, Zinman L, Moreno D, Schymick J, et al. Hypermethylation of the CpG Island Near the G4C2 Repeat in ALS with a C9orf72 Expansion. Am J Hum Genet 2013 May 22 [Epub ahead of print].Google Scholar
  77. 77.
    Chan A, Shea TB. Folate deprivation increases presenilin expression, gamma-secretase activity, and Abeta levels in murine brain: potentiation by ApoE deficiency and alleviation by dietary S-adenosyl methionine. J Neurochem 2007;102:753–760.PubMedGoogle Scholar
  78. 78.
    Fuso A, Seminara L, Cavallaro RA, D’Anselmi F, Scarpa S. S-adenosylmethionine/homocysteine cycle alterations modify DNA methylation status with consequent deregulation of PS1 and BACE and beta-amyloid production. Mol Cell Neurosci 2005;28:195–204.PubMedGoogle Scholar
  79. 79.
    Fuso A, Nicolia V, Cavallaro RA, et al. B-vitamin deprivation induces hyperhomocysteinemia and brain S-adenosylhomocysteine, depletes brain S-adenosylmethionine, and enhances PS1 and BACE expression and amyloid-beta deposition in mice. Mol Cell Neurosci 2008;37:731–746.PubMedGoogle Scholar
  80. 80.
    Lin H-C, Hsieh H-M, Chen Y-H, Hu M-L. S-Adenosylhomocysteine increases beta-amyloid formation in BV-2 microglial cells by increased expressions of beta-amyloid precursor protein and presenilin 1 and by hypomethylation of these gene promoters. Neurotoxicology 2009;30:622–627.PubMedGoogle Scholar
  81. 81.
    Scarpa S, Fuso A, D’Anselmi F, Cavallaro RA. Presenilin 1 gene silencing by S-adenosylmethionine: a treatment for Alzheimer disease? FEBS Lett 2003;541:145–148.PubMedGoogle Scholar
  82. 82.
    Bihaqi SW, Zawia NH. Alzheimer’s disease biomarkers and epigenetic intermediates following exposure to Pb in vitro. Curr Alzheimer Res 2012;9:555–562.PubMedGoogle Scholar
  83. 83.
    Li Y-Y, Chen T, Wan Y, Xu S. Lead exposure in pheochromocytoma cells induces persistent changes in amyloid precursor protein gene methylation patterns. Environ Toxicol 2012;27:495–502.PubMedGoogle Scholar
  84. 84.
    Guo X, Wu X, Ren L, Liu G, Li L. Epigenetic mechanisms of amyloid-β production in anisomycin-treated SH-SY5Y cells. Neuroscience 2011;194:272–281.PubMedGoogle Scholar
  85. 85.
    Rao JS, Keleshian VL, Klein S, Rapoport SI. Epigenetic modifications in frontal cortex from Alzheimer ’ s disease and bipolar disorder patients. Transl Psychiatry 2012;2:1–7.Google Scholar
  86. 86.
    Tahiliani M, Koh KP, Shen Y, et al. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 2009;324:930–935.PubMedGoogle Scholar
  87. 87.
    Mastroeni D, McKee A, Grover A, Rogers J, Coleman PD. Epigenetic differences in cortical neurons from a pair of monozygotic twins discordant for Alzheimer’s disease. PloS One 2009;4:e6617.PubMedGoogle Scholar
  88. 88.
    Sandi C, Al-Mahdawi S, Pook MA. Epigenetics in Friedreich’s ataxia: challenges and opportunities for therapy. Genet Res Int 2013;852080.Google Scholar
  89. 89.
    Chiurazzi P, Pomponi MG, Willemsen R, Oostra BA, Neri G. In vitro reactivation of the FMR1 gene involved in fragile X syndrome. Hum Mol Genet 1998;7:109–113.PubMedGoogle Scholar
  90. 90.
    Chiurazzi P, Grazia Pomponi M, Pietrobono R, Bakker CE, Neri G, Oostra BA. Synergistic effect of histone hyperacetylation and DNA demethylation in the reactivation of the FMR1 gene. Hum Mol Genet 1999;8:2317–2323.PubMedGoogle Scholar
  91. 91.
    Rice JC, Briggs SD, Ueberheide B, et al. Histone methyltransferases direct different degrees of methylation to define distinct chromatin domains. Mol Cell 2003;12:1591–1598.PubMedGoogle Scholar
  92. 92.
    Gräff J, Tsai L-H. The potential of HDAC inhibitors as cognitive enhancers. Annu Rev Pharmacol Toxicol 2013;53:311–330.PubMedGoogle Scholar
  93. 93.
    Haberland M, Montgomery RL, Olson EN. The many roles of histone deacetylases in development and physiology: implications for disease and therapy. Nat Rev Genet 2009;10:32–42.PubMedGoogle Scholar
  94. 94.
    Struhl K. Histone acetylation and transcriptional regulatory mechanisms. Genes Develop 1998;12:599–606.PubMedGoogle Scholar
  95. 95.
    Kubicek S, Gilbert JC, Fomina-Yadlin D, et al. Chromatin-targeting small molecules cause class-specific transcriptional changes in pancreatic endocrine cells. Proce Natl Acad Sci U S A 2012;109:5364–5369.Google Scholar
  96. 96.
    Koolen DA, Kramer JM, Neveling K, et al. Mutations in the chromatin modifier gene KANSL1 cause the 17q21.31 microdeletion syndrome. Nat Genet 2012;44:639–641.PubMedGoogle Scholar
  97. 97.
    Kerimoglu C, Agis-Balboa RC, Kranz A, et al. Histone-methyltransferase MLL2 (KMT2B) is required for memory formation in mice. J Neurosci  2013;33:3452–3464.PubMedGoogle Scholar
  98. 98.
    Korzus E, Rosenfeld MG, Mayford M. CBP histone acetyltransferase activity is a critical component of memory consolidation. Neuron 2004;42:961–972.PubMedGoogle Scholar
  99. 99.
    Broide RS, Redwine JM, Aftahi N, Young W, Bloom FE, Winrow CJ. Distribution of histone deacetylases 1–11 in the rat brain. J Mol Neurosci 2007;31:47–58.PubMedGoogle Scholar
  100. 100.
    McQuown SC, Barrett RM, Matheos DP, et al. HDAC3 is a critical negative regulator of long-term memory formation. J Neurosci 2011;31:764–774.PubMedGoogle Scholar
  101. 101.
    Nelson ED, Bal M, Kavalali ET, Monteggia LM. Selective impact of MeCP2 and associated histone deacetylases on the dynamics of evoked excitatory neurotransmission. J Neurophysiol 2011;106:193–201.PubMedGoogle Scholar
  102. 102.
    Guan J-S, Haggarty SJ, Giacometti E, et al. HDAC2 negatively regulates memory formation and synaptic plasticity. Nature 2009;459:55–60.PubMedGoogle Scholar
  103. 103.
    Levenson JM, O’Riordan KJ, Brown KD, Trinh MA, Molfese DL, Sweatt JD. Regulation of histone acetylation during memory formation in the hippocampus. J Biol Chem 2004;279:40545–40559.PubMedGoogle Scholar
  104. 104.
    Gräff J, Rei D, Guan J-S, et al. An epigenetic blockade of cognitive functions in the neurodegenerating brain. Nature 2012;483:222–226.PubMedGoogle Scholar
  105. 105.
    Haggarty SJ, Tsai L-H. Probing the role of HDACs and mechanisms of chromatin-mediated neuroplasticity. Neurobiol Learn Mem 2011;96:41–52.PubMedGoogle Scholar
  106. 106.
    Ding H, Dolan PJ, Johnson GVW. Histone deacetylase 6 interacts with the microtubule-associated protein tau. J Neurochem 2008;106:2119–2130.PubMedGoogle Scholar
  107. 107.
    Govindarajan N, Rao P, Burkhardt S, et al. Reducing HDAC6 ameliorates cognitive deficits in a mouse model for Alzheimer’s disease. EMBO Mol Med 2013;5:52–63.PubMedGoogle Scholar
  108. 108.
    Kim M-S, Akhtar MW, Adachi M, et al. An essential role for histone deacetylase 4 in synaptic plasticity and memory formation. J Neurosci 2012;32: 10879–10886.PubMedGoogle Scholar
  109. 109.
    Harrison IF, Dexter DT. Epigenetic targeting of histone deacetylase: Therapeutic potential in Parkinson’s disease? Pharmacol Ther 2013 May 24 [Epub ahead of print].Google Scholar
  110. 110.
    Bradner JE, West N, Grachan ML, et al. Chemical phylogenetics of histone deacetylases. Nat Chem Biol 2010;6:238–243.PubMedGoogle Scholar
  111. 111.
    Fischer A, Sananbenesi F, Wang X, Dobbin M, Tsai L-H. Recovery of learning and memory is associated with chromatin remodelling. Nature 2007;447:178–182.PubMedGoogle Scholar
  112. 112.
    Morris MJ, Mahgoub M, Na ES, Pranav H, Monteggia LM. Loss of histone deacetylase 2 improves working memory and accelerates extinction learning. J Neurosci 2013;33:6401–6411.PubMedGoogle Scholar
  113. 113.
    Kim D, Frank CL, Dobbin MM, et al. Deregulation of HDAC1 by p25/Cdk5 in neurotoxicity. Neuron 2008;60:803–817.PubMedGoogle Scholar
  114. 114.
    Cenik B, Sephton CF, Dewey CM, et al. Suberoylanilide hydroxamic acid (vorinostat) up-regulates progranulin transcription: rational therapeutic approach to frontotemporal dementia. J Biol Chem 2011;286:16101–16108.PubMedGoogle Scholar
  115. 115.
    Min S-W, Cho S-H, Zhou Y, et al. Acetylation of tau inhibits its degradation and contributes to tauopathy. Neuron 2010;67:953–966.PubMedGoogle Scholar
  116. 116.
    Krichevsky AM, Sonntag K-C, Isacson O, Kosik KS. Specific microRNAs modulate embryonic stem cell-derived neurogenesis. Stem Cells 2006;24:857–864.PubMedGoogle Scholar
  117. 117.
    De Pietri Tonelli D, Pulvers JN, Haffner C, Murchison EP, Hannon GJ, Huttner WB. miRNAs are essential for survival and differentiation of newborn neurons but not for expansion of neural progenitors during early neurogenesis in the mouse embryonic neocortex. Development 2008;135:3911–3921PubMedGoogle Scholar
  118. 118.
    Coppedè F. Advances in the Genetics and Epigenetics of Neurodegenerative Diseases. Epigenet Neurodegener Dis 2013;1:2–30.Google Scholar
  119. 119.
    Hébert SS, Papadopoulou AS, Smith P, et al. Genetic ablation of Dicer in adult forebrain neurons results in abnormal tau hyperphosphorylation and neurodegeneration. Hum Mol Genet 2010;19:3959–3969.PubMedGoogle Scholar
  120. 120.
    Cogswell JP, Ward J, Taylor IA, et al. Identification of miRNA changes in Alzheimer’s disease brain and CSF yields putative biomarkers and insights into disease pathways. J Alzheimers Dis 2008;14:27–41.PubMedGoogle Scholar
  121. 121.
    Julien C, Tremblay C, Emond V, et al. Sirtuin 1 reduction parallels the accumulation of tau in Alzheimer disease. J Neuropathol Exp Neurol 2009;68:48–58.PubMedGoogle Scholar
  122. 122.
    Renoux AJ, Todd PK. Neurodegeneration the RNA way. Prog Neurobiol 2012;97:173–189.PubMedGoogle Scholar
  123. 123.
    Tan L, Yu J-T, Hu N, Tan L. Non-coding RNAs in Alzheimer’s disease. Mol Neurobiol 2013;47:382–393.PubMedGoogle Scholar
  124. 124.
    Hébert SS, Horré K, Nicolaï L, et al. Loss of microRNA cluster miR-29a/b-1 in sporadic Alzheimer’s disease correlates with increased BACE1/beta-secretase expression. Proc Natl Acad Sci U S A 2008;105:6415–6420.PubMedGoogle Scholar
  125. 125.
    Yao J, Hennessey T, Flynt A, Lai E, Beal MF, Lin MT. MicroRNA-related cofilin abnormality in Alzheimer’s disease. PloS One 2010;5:e15546.PubMedGoogle Scholar
  126. 126.
    Boissonneault V, Plante I, Rivest S, Provost P. MicroRNA-298 and microRNA-328 regulate expression of mouse beta-amyloid precursor protein-converting enzyme 1. J Biol Chem 2009;284:1971–1981.PubMedGoogle Scholar
  127. 127.
    Wang W-X, Rajeev BW, Stromberg AJ, et al. The expression of microRNA miR-107 decreases early in Alzheimer’s disease and may accelerate disease progression through regulation of beta-site amyloid precursor protein-cleaving enzyme 1. J Neurosci 2008;28:1213–1223.PubMedGoogle Scholar
  128. 128.
    Hébert SS, Horré K, Nicolaï L, et al. MicroRNA regulation of Alzheimer’s Amyloid precursor protein expression. Neurobiol Dis 2009;33:422–428.PubMedGoogle Scholar
  129. 129.
    Long JM, Lahiri DK. MicroRNA-101 downregulates Alzheimer’s amyloid-β precursor protein levels in human cell cultures and is differentially expressed. Biochem Biophys Res Commun 2011;404:889–895.PubMedGoogle Scholar
  130. 130.
    Faghihi MA, Modarresi F, Khalil AM, et al. Expression of a noncoding RNA is elevated in Alzheimer’s disease and drives rapid feed-forward regulation of beta-secretase. Nat Med 2008;14:723–730.PubMedGoogle Scholar
  131. 131.
    Saxena A, Carninci P. Long non-coding RNA modifies chromatin: epigenetic silencing by long non-coding RNAs. Bioessays  2011;33:830–839.PubMedGoogle Scholar
  132. 132.
    Fang M, Wang J, Zhang X, et al. The miR-124 regulates the expression of BACE1/β-secretase correlated with cell death in Alzheimer’s disease. Toxicol Lett 2012;209:94–105.PubMedGoogle Scholar
  133. 133.
    Perry MM, Williams AE, Tsitsiou E, Larner-Svensson HM, Lindsay MA. Divergent intracellular pathways regulate interleukin-1beta-induced miR-146a and miR-146b expression and chemokine release in human alveolar epithelial cells. FEBS Lett 2009;583:3349–3355.PubMedGoogle Scholar
  134. 134.
    Taganov KD, Boldin MP, Chang K-J, Baltimore D. NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci U S A 2006;103:12481–12486.PubMedGoogle Scholar
  135. 135.
    Tollervey JR, Curk T, Rogelj B, et al. Characterizing the RNA targets and position-dependent splicing regulation by TDP-43. Nat Neurosci 2011;14:452–458.PubMedGoogle Scholar
  136. 136.
    Kawahara Y, Mieda-Sato A. TDP-43 promotes microRNA biogenesis as a component of the Drosha and Dicer complexes. Proc Natl Acad Sci U S A 2012;109:3347–3352.PubMedGoogle Scholar
  137. 137.
    Lai CP-K, Breakefield XO. Role of exosomes/microvesicles in the nervous system and use in emerging therapies. Front Physiol 2012;3:228.PubMedGoogle Scholar
  138. 138.
    Modarresi F, Faghihi MA, Lopez-Toledano MA, et al. Inhibition of natural antisense transcripts in vivo results in gene-specific transcriptional upregulation. Nat Biotechnol 2012;30:453–459.PubMedGoogle Scholar
  139. 139.
    Pardridge WM. The blood–brain barrier: bottleneck in brain drug development. NeuroRx 2005;2:3–14.PubMedGoogle Scholar
  140. 140.
    Hockly E, Richon VM, Woodman B, et al. Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, ameliorates motor deficits in a mouse model of Huntington’s disease. Proc Natl Acad Sci U S A 2003;100:2041–2046.PubMedGoogle Scholar
  141. 141.
    Kwa FAA, Balcerczyk A, Licciardi P, El-Osta A, Karagiannis TC. Chromatin modifying agents - the cutting edge of anticancer therapy. Drug Discov Today 2011;16:543–547.PubMedGoogle Scholar
  142. 142.
    Rai M, Soragni E, Jenssen K, et al. HDAC inhibitors correct frataxin deficiency in a Friedreich ataxia mouse model. PloS One 2008;3:e1958.PubMedGoogle Scholar
  143. 143.
    Cuadrado-Tejedor M, Oyarzabal J, Lucas MP, Franco R, García-Osta A. Epigenetic drugs in Alzheimer’s disease. BioMolecular Concepts 2013 Jul 27 [Epub ahead of print].Google Scholar
  144. 144.
    Martinet N, Michel BY, Bertrand P, Benhida R. Small molecules DNA methyltransferases inhibitors. Med Chem Comm 2011;3:263.Google Scholar
  145. 145.
    Subramanian S, Bates SE, Wright JJ, Espinoza-Delgado I, Piekarz RL. Clinical toxicities of histone deacetylase inhibitors. Pharmaceuticals 2010;3:2751–2767.Google Scholar
  146. 146.
    Petruccelli LA, Dupéré-Richer D, Pettersson F, Retrouvey H, Skoulikas S, Miller WH. Vorinostat induces reactive oxygen species and DNA damage in acute myeloid leukemia cells. PloS One 2011;6:e20987.PubMedGoogle Scholar
  147. 147.
    Alzoubi KH, Khabour OF, Jaber AG, Al-Azzam SI, Mhaidat NM, Masadeh MM. Tempol prevents genotoxicity induced by vorinostat: role of oxidative DNA damage. Cytotechnology 2013 Jun 13 [Epub ahead of print].Google Scholar
  148. 148.
    Kreuter J. Nanoparticulate systems for brain delivery of drugs. Adv Drug Deliv Rev 2001;47:65–81.PubMedGoogle Scholar
  149. 149.
    Kumar P, Wu H, McBride JL, et al. Transvascular delivery of small interfering RNA to the central nervous system. Nature 2007;448:39–43.PubMedGoogle Scholar
  150. 150.
    Pardridge WM. Intravenous, non-viral RNAi gene therapy of brain cancer. Exp Opin Biol Ther 2004;4:1103–1113.Google Scholar
  151. 151.
    Masserini M. Nanoparticles for brain drug delivery. ISRN Biochemistry 2013; 1–18.Google Scholar
  152. 152.
    Pastori C, Wahlestedt C. Involvement of long noncoding RNAs in diseases affecting the central nervous system. RNA Biology 2012;9:860–870.PubMedGoogle Scholar
  153. 153.
    Miller CP, Singh MM, Rivera-Del Valle N, Manton CA, Chandra J. Therapeutic strategies to enhance the anticancer efficacy of histone deacetylase inhibitors. J Biomed Biotechnol 2011;514261.Google Scholar
  154. 154.
    Bohacek J, Mansuy IM. Epigenetic inheritance of disease and disease risk. Neuropsychopharmacology 2013;38:220–236.PubMedGoogle Scholar
  155. 155.
    Hackett JA, Sengupta R, Zylicz JJ, et al. Germline DNA demethylation dynamics and imprint erasure through 5-hydroxymethylcytosine. Science 2013;339:448–452.PubMedGoogle Scholar

Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc. 2013

Authors and Affiliations

  • Chendhore S. Veerappan
    • 1
  • Sama Sleiman
    • 2
  • Giovanni Coppola
    • 1
    • 3
  1. 1.Semel Institute for Neuroscience and Human BehaviorDavid Geffen School of Medicine at UCLALos AngelesUSA
  2. 2.Burke Research CenterWeill Medical College of Cornell UniversityWhite PlainsUSA
  3. 3.Program in Neurogenetics, Department of NeurologyDavid Geffen School of Medicine at UCLALos AngelesUSA

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