Epigenetic drug discovery for Alzheimer's disease

Expert Opinion on Drug Discovery

Volumn 9, Issue 9, 2014, Pages 1059-1086

  Cacabelos, Ramón ^a,b   Torrellas, Clara ^b  

^a CAMILO JOSÉ CELA UNIVERSITY   (Spain)

^b Centro de Investigacion Biomedica EuroEspes   (Spain)

Author keywords

Alzheimer's disease; DNA methyltransferase inhibitors; Epigenetic drugs; Histone acetyltransferase activators; Histone deacetylase inhibitors; Histone demethylase inhibitors; Histone methyltransferase inhibitors; MicroRNAs; Non coding RNAs; Pharmacogenetics

Indexed keywords

ACYLTRANSFERASE INHIBITOR; CENTRAL NERVOUS SYSTEM AGENTS; CYTOCHROME; DNA METHYLTRANSFERASE INHIBITOR; EPIGENETIC DRUG; FOLIC ACID; HISTONE ACETYLTRANSFERASE INHIBITOR; HISTONE DEACETYLASE INHIBITOR; HISTONE DEMETHYLASE INHIBITOR; HISTONE METHYLTRANSFERASE INHIBITOR; METHYLTRANSFERASE INHIBITOR; MICRORNA; NOOTROPIC AGENT; OXYGENASE INHIBITOR; UNCLASSIFIED DRUG; UNTRANSLATED RNA; VITAMIN B GROUP; XENOBIOTIC AGENT;

ALZHEIMER DISEASE; CONFUSION; DIET; DNA MODIFICATION; DRUG CLASSIFICATION; DRUG DEVELOPMENT; DRUG EFFICACY; DRUG MECHANISM; DRUG SAFETY; DRUG TARGETING; EEG ABNORMALITY; EPIGENETICS; FATIGUE; GENE EXPRESSION; HISTONE MODIFICATION; HUMAN; LIVER TOXICITY; NONHUMAN; PHARMACOEPIGENETICS; PHARMACOGENETICS; PHARMACOGENOMICS; PRIORITY JOURNAL; REVIEW; THROMBOCYTOPENIA; ANIMAL; DRUG DESIGN; GENE EXPRESSION REGULATION; GENETIC EPIGENESIS; GENETICS; PATHOPHYSIOLOGY; PROCEDURES;

ALZHEIMER DISEASE; ANIMALS; DRUG DESIGN; DRUG DISCOVERY; EPIGENESIS, GENETIC; EPIGENOMICS; GENE EXPRESSION REGULATION; HUMANS; PHARMACOGENETICS;

EID: 84906335678     PISSN: 17460441     EISSN: 1746045X     Source Type: Journal    
DOI: 10.1517/17460441.2014.930124     Document Type: Review

References (174)

1. Suehs BT, Davis CD, Alvir J, et al. The clinical and economic burden of newly diagnosed Alzheimers disease in a medicare advantage population. Am J Alzheimers Dis Other Demen 2013;28:384-92
2. Centers for Disease Control and Prevention. National Center for Health Statistics (NCHS). Atlanta, GA, USA Available from: www.cdc.gov/nchs/[Last accessed 10 January 2014]
3. Cacabelos R. Pharmacogenomics in Alzheimers disease. Methods Mol Biol 2008;448:213-357
4. Cacabelos R. Alzheimers disease 2011: where are we heading? Gen-T 2011;8:54-86
5. Cacabelos R. The path to personalized medicine in mental disorders. In: Ritsner MS, editor. The handbook of neuropsychiatric biomarkers, endophenotypes and genes. Volume 4 Springer; Netherlands: 2011. p. 3-63
6. Cacabelos R. Pharmacogenetic basis for therapeutic optimization in Alzheimers disease. Mol Diagn Ther 2007;11:385-405 (Pubitemid 350274406)
7. Cacabelos R. Pharmacogenomics and therapeutic prospects in dementia. Eur Arch Psychiatry Clin Neurosci 2008;258(Suppl 1):28-47 (Pubitemid 351424036)
8. Cacabelos R, Fernández-Novoa L, Lombardi V, et al. Molecular genetics of Alzheimers disease and aging. Methods Find Exp Clin Pharmacol 2005;27(Suppl A):1-573
9. Qureshi IA, Mehler MF. Advances in epigenetics and epigenomics for neurodegenerative diseases. Curr Neurol Neurosci Rep 2011;11:464-73
10. Enciu AM, Popescu BO, Gheorghisan-Galateanu A. MicroRNAs in brain development and degeneration. Mol Biol Rep 2012;39:2243-52
11. Wang J, Yu JT, Tan MS, et al. Epigenetic mechanisms in Alzheimers disease: implications for pathogenesis and therapy. Ageing Res Rev 2013;12(4):1024-41
12. Dambacher S, de Almeida GP, Schotta G. Dynamic changes of the epigenetic landscape during cellular differentiation. Epigenomics 2013;5(6):701-13
13. Cacabelos R, Cacabelos P, Torrellas C, et al. Pharmacogenomics of Alzheimers disease. Novel therapeutic strategies for drug development. Methods Mol Biol 2014;In press
14. Kubota T, Takae H, Miyake K. Epigenetic mechanisms and therapeutic perspectives for neurodevelopmental disorders. Pharmaceuticals (Basel) 2012;5(4):369-83
15. Konsoula Z, Barile FA. Epigenetic histone acetylation and deacetylation mechanisms in experimental models of neurodegenerative disorders. J Pharmacol Toxicol Methods 2012;66(3):215-20
16. Chouliaras L, Rutten BP, Kenis G, et al. Epigenetic regulation in the pathophysiology of Alzheimers disease. Prog Neurobiol 2010;90(4):498-510
17. Xu K, Dai XL, Huang HC, Jiang ZF. Targeting HDACs: a promising therapy for Alzheimers disease. Oxid Med Cell Longev 2011;2011:143269
18. Gräff J, Tsai LH. The potential of HDAC inhibitors as cognitive enhancers. Annu Rev Pharmacol Toxicol 2013;53:311-30
19. Adwan L, Zawia NH. Epigenetics: a novel therapeutic approach for the treatment of Alzheimers disease. Pharmacol Ther 2013;139(1):41-50
20. Helin K, Dhanak D. Chromatin proteins and modifications as drug targets. Nature 2013;502(7472):480-8
21. Peedicayil J. Epigenetic drugs in cognitive disorders. Curr Pharm Des 2014;20(11):1840-6
22. Chuang DM, Leng Y, Marinova Z, et al. Multiple roles of HDAC inhibition in neurodegenerative conditions. Trends Neurosci 2009;32(11):591-601
23. Gapp K, Woldemichael BT, Bohacek J, Mansuy IM. Epigenetic regulation in neurodevelopment and neurodegenerative diseases. Neuroscience 2014;264:99-111
24. Lötsch J, Schneider G, Reker D, et al. Common non-epigenetic drugs as epigenetic modulators. Trends Mol Med 2013;19(12):742-53
25. Kelly TK, De Carvalho DD, Jones PA. Epigenetic modifications as therapeutic targets. Nat Biotechnol 2010;28(10):1069-78
26. Bertram L, McQueen MB, Mullin K, et al. Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database. Nat Genet 2007;39:17-23 (Pubitemid 46026496)
27. Cacabelos R. The application of functional genomics to Alzheimers disease. Pharmacogenomics 2003;4:597-621 (Pubitemid 37120947)
28. Cacabelos R. Pharmacogenomics and therapeutic prospects in Alzheimers disease. Expert Opin Pharmacother 2005;6:1967-87 (Pubitemid 41613329)
29. Cacabelos R. Pharmacogenomics and therapeutic strategies for dementia. Expert Rev Mol Diagn 2009;9:567-611
30. Cacabelos R, Martínez-Bouza R. Genomics and pharmacogenomics of dementia. CNS Neurosci Ther 2011;17:566-76
31. Larner AJ. Presenilin-1 mutations in Alzheimers disease: an update on genotype-phenotype relationships. J Alzheimers Dis 2013;37(4):653-9
32. Hooli BV, Kovacs-Vajna ZM, Mullin K, et al. Rare autosomal copy number variations in early-onset familial Alzheimers disease. Mol Psychiatry 2014;19(6):676-81
33. Zou F, Belbin O, Carrasquillo MM, et al. Linking protective GAB2 variants, increased cortical GAB2 expression and decreased Alzheimers disease pathology. PLoS ONE 2013;8:e64802
34. Wang YL, Tan MS, Yu JT, et al. Toll-like receptor 9 promoter polymorphism is associated with decreased risk of Alzheimers disease in Han Chinese. J Neuroinflammation 2013;10:101
35. Li HL, Lu SJ, Sun YM, et al. The LRRK2 R1628P variant plays a protective role in Han Chinese population with Alzheimers disease. CNS Neurosci Ther 2013;19:207-15
36. Takeda M, Martínez R, Kudo T, et al. Apolipoprotein E and central nervous system disorders: reviews of clinical findings. Psychiatry Clin Neurosci 2010;64:592-607
37. Cacabelos R. Pharmacogenomics of central nervous system (CNS) drugs. Drug Dev Res 2012;73:461-76
38. Cacabelos R, Fernández-Novoa L, Martínez-Bouza R, et al. Future trends in the pharmacogenomics of brain disorders and dementia: influence of APOE and CYP2D6 variants. Pharmaceuticals 2010;3:3040-100
39. Phillips NR, Simpkins JW, Roby RK. Mitochondrial DNA deletions in Alzheimers brains: a review. Alzheimers Dement 2014;10(3):393-400
40. Lagouge M, Larsson NG. The role of mitochondrial DNA mutations and free radicals in disease and ageing. J Intern Med 2013;273:529-43
41. Szulwach KE, Jin P. Integrating DNA methylation dynamics into a framework for understanding epigenetic codes. Bioessays 2014;36(1):107-17
42. Laurent L, Wong E, Li G, et al. Dynamic changes in the human methylome during differentiation. Genome Res 2010;20(3):320-31
43. Nebbioso A, Carafa V, Benedetti R, Altucci L. Trials with epigenetic drugs: an update. Mol Oncol 2012;6:657-82
44. Cuadrado-Tejedor M, Oyarzabal J, Pascual Lucas M, et al. Epigenetic drugs in Alzheimers disease. BioMol Concepts 2013;4(5):433-45
45. Mikaelsson MA, Miller CA. The path to epigenetic treatment of memory disorders. Neurobiol Learn Mem 2011;96(1):13-18
46. Clapier CR, Cairns BR. The biology of chromatin remodeling complexes. Ann Rev Biochem 2009;78:273-304
47. Huynh JL, Casaccia P. Epigenetic mechanisms in multiple sclerosis: implications for pathogenesis and treatment. Lancet Neurol 2013;12:195-206
48. Ernst C, Morton CC. Identification and function of long non-coding RNA. Front Cell Neurosci 2013;7:168
49. Li LC. Chromatin remodeling by the small RNA machinery in mammalian cells. Epigenetics 2014;9(1):45-52
50. Jiao AL, Slack FJ. RNA-mediated gene activation. Epigenetics 2014;9(1):27-36
51. Wu P, Zuo X, Deng H, et al. Roles of long noncoding RNAs in brain development, functional diversification and neurodegenerative diseases. Brain Res Bull 2013;97:69-80
52. Van den Hove DL, Kompotis K, Lardenoije R, et al. Epigenetically regulated microRNAs in Alzheimers disease. Neurobiol Aging 2014;35(4):731-45
53. Brochier C, Langley B. Chromatin modifications associated with DNA double-strand breaks repair as potential targets for neurological diseases. Neurotherapeutics 2013;10(4):817-30
54. Coppedè F, Migliore L. Evidence linking genetics, environment, and epigenetics to impaired DNA repair in Alzheimers disease. J Alzheimers Dis 2010;20(4):953-66
55. Mastroeni D, Grover A, Delvaux E, et al. Epigenetic mechanisms in Alzheimers disease. Neurobiol Aging 2011;32:1161-80
56. Chouliaras L, Mastroeni D, Delvaux E, et al. Consistent decrease in global DNA methylation and hydroxymethylation in the hippocampus of Alzheimers disease patients. Neurobiol Aging 2013;34(9):2091-9
57. Zhang K, Schrag M, Crofton A, et al. Targeted proteomics for quantification of histone acetylation in Alzheimers disease. Proteomics 2012;12:1261-8
58. Ding H, Dolan PJ, Johnson GVW. Histone deacetylase 6 interacts with the microtubule-associated protein tau. Neurochem 2008;106(5):2119-30
59. Govindarajan N, Rao P, Burkhardt S, et al. Reducing HDAC6 ameliorates cognitive deficits in a mouse model for Alzheimers disease. EMBO Mol Med 2013;5:52-63
60. Julien C, Tremblay C, Emond V. SIRT1 decrease parallels the accumulation of tau in alzheimer disease. J Neuropathol Exp Neurol 2009;68(1):48-58
61. Donmez G, Wang D, Cohen DE, Guarente L. SIRT1 suppresses-amyloid production by activating the -secretase gene ADAM10. Cell 2010;142(2):320-32
62. Ryu H, Barrup M, Kowall NW, McKee AC. P3-260: epigenetic modification in a monozygotic twin with Alzheimers disease. Alzheimers Dement 2008;4:T598
63. Ogawa O, Zhu X, Lee HG, et al. Ectopic localization of phosphorylated histone H3 in Alzheimers disease: a mitotic catastrophe? Acta Neuropathol 2003;105(5):524-8 (Pubitemid 36798850)
64. Myung NH, Zhu X, Kruman II. Evidence of DNA damage in Alzheimer disease: phosphorylation of histone H2AX in astrocytes. Age (Dordr) 2008;30(4):209-15
65. Francis YI, Fà M, Ashraf H, et al. Dysregulation of histone acetylation in the APP/PS1 mouse model of Alzheimers disease. J Alzheimers Dis 2009;18(1):131-9
66. Walker MP, LaFerla FM, Oddo SS, Brewer GJ. Reversible epigenetic histone modifications and Bdnf expression in neurons with aging and from a mouse model of Alzheimers disease. Age (Dordr) 2013;35(3):519-31
67. Liu R, Lei JX, Luo C, et al. Increased EID1 nuclear translocation impairs synaptic plasticity and memory function associated with pathogenesis of Alzheimers disease. Neurobiol Dis 2012;45(3):902-12
68. Koshibu K, Gräff J, Beullens M, et al. Protein phosphatase 1 regulates the histone code for long-term memory. J Neurosci 2009;29(41):13079-89
69. Peleg S, Sananbenesi F, Zovoilis A, et al. Altered histone acetylation is associated with age-dependent memory impairment in mice. Science 2010;328(5979):753-6
70. Fischer A, Sananbenesi F, Wang X, et al. Recovery of learning and memory is associated with chromatin remodelling. Nature 2007;447:178-82 (Pubitemid 46763080)
71. Guan JS, Haggarty SJ, Giacometti E, et al. HDAC2 negatively regulates memory formation and synaptic plasticity. Nature 2009;459(7243):55-60
72. Gräff J, Rei D, Guan JS, et al. An epigenetic blockade of cognitive functions in the neurodegenerating brain. Nature 2012;483(7388):222-6
73. Kim MS, Akhtar MW, Adachi M, et al. An essential role for histone deacetylase 4 in synaptic plasticity and memory formation. J Neurosci 2012;32(32):10879-86
74. Ishimaru N, Fukuchi M, Hirai A, et al. Differential epigenetic regulation of BDNF and NT-3 genes by trichostatin A and 5-aza-2-deoxycytidine in Neuro- 2a cells. Biochem Biophys Res Commun 2010;394(1):173-7
75. Tian F, Marini AM, Lipsky RH. Effects of histone deacetylase inhibitor trichostatin A on epigenetic changes and transcriptional activation of Bdnf promoter 1 by rat hippocampal neurons. Ann N Y Acad Sci 2010;1199:186-93
76. Gupta S, Kim SY, Artis S, et al. Histone methylation regulates memory formation. J Neurosci 2010;30(10):3589-99
77. Lithner CU, Hernandez CM, Nordberg A, Sweatt JD. Epigenetic changes related to beta-amyloid-implications for Alzheimers disease. Alzheimers Dement 2009;5:P304
78. Mallick B, Ghosh Z. A complex crosstalk between polymorphic microRNA target sites and AD prognosis. RNA Biol 2011;8:665-73
79. Long JM, Lahiri DK. MicroRNA-101 downregulates Alzheimers amyloid- precursor protein levels in human cell cultures and is differentially expressed. Biochem Biophys Res Commun 2011;404(4):889-95
80. Liu W, Liu C, Zhu J, et al. MicroRNA-16 targets amyloid precursor protein to potentially modulate Alzheimers-associated pathogenesis in SAMP8 mice. Neurobiol Aging 2012;33(3):522-34
81. Smith P, Al Hashimi A, Girard J, et al. In vivo regulation of amyloid precursor protein neuronal splicing by microRNAs. J Neurochem 2011;116(2):240-7
82. Fang M, Wang J, Zhang X. The miR- 124 regulates the expression of BACE1/- secretase correlated with cell death in Alzheimers disease. Toxicol Lett 2012;209(1):94-105
83. Hébert SS, Horré K, Nicolaï L, et al. Loss of microRNA cluster miR-29a/b- 1 in sporadic Alzheimers disease correlates with increased BACE1/- secretase expression. Proc Natl Acad Sci USA 2008;105(17):6415-20 (Pubitemid 351758360)
84. Zong Y, Wang H, Dong W, et al. miR-29c regulates BACE1 protein expression. Brain Res 2011;1395:108-15
85. Wang WX, Rajeev BW, Stromberg AJ, et al. The expression of microRNA miR- 107 decreases early in Alzheimers disease and may accelerate disease progression through regulation of -site amyloid precursor protein-cleaving enzyme 1. J Neurosci 2008;28(5):1213-23 (Pubitemid 351186356)
86. Boissonneault V, Plante I, Rivest S, Provost P. MicroRNA-298 and microRNA-328 regulate expression of mouse beta-amyloid precursor proteinconverting enzyme 1. J Biol Chem 2009;284(4):1971-81
87. Zhu HC, Wang LM, Wang M, et al. MicroRNA-195 downregulates Alzheimers disease amyloid-production by targeting BACE1. Brain Res Bull 2012;88(6):596-601
88. Faghihi MA, Modarresi F, Khalil AM, et al. Expression of a noncoding RNA is elevated in Alzheimers disease and drives rapid feed-forward regulation of beta-secretase. Nat Med 2008;14(7):723-30
89. Faghihi MA, Zhang M, Huang J, et al. Research evidence for natural antisense transcript-mediated inhibition of microRNA function. Genome Biol 2010;11(5):R56
90. Massone S, Ciarlo E, Vella S, et al. NDM29, A RNA polymerase IIIdependent non coding RNA, promotes amyloidogenic processing of amyloid precursor protein (APP) and amyloid secretion. Biochim Biophys Acta 2012;1823(7):1170-7
91. Wang WX, Huang Q, Hu Y, et al. Patterns of microRNA expression in normal and early Alzheimers disease human temporal cortex: white matter versus gray matter. Acta Neuropathol 2011;121(2):193-205
92. Wang WX, Wilfred BR, Madathil SK, et al. miR-107 regulates granulin/progranulin with implications for traumatic brain injury and neurodegenerative disease. Am J Pathol 2010;177(1):334-45
93. Geekiyanage H, Chan C MicroRNA- 137/181c regulates serine palmitoyltransferase and in turn amyloid, novel targets in sporadic Alzheimers Disease. J Neurosci 2011;31(41):14820-30
94. Akram A, Schmeidler J, Katsel P, et al. Increased expression of cholesterol transporter ABCA1 is highly correlated with severity of dementia in AD hippocampus. Brain Res 2010;1318:167-77
95. Massone S, Vassallo I, Fiorino G, et al. 17A, a novel non-coding RNA, regulates GABA B alternative splicing and signaling in response to inflammatory stimuli and in Alzheimer disease. Neurobiol Dis 2011;41(2):308-17
96. Issa JP, Garcia-Manero G, Giles FJ, et al. Phase 1 study of low-dose prolonged exposure schedules of the hypomethylating agent 5-aza-2- deoxycytidine (decitabine) in hematopoietic malignancies. Blood 2004;103(5):1635-40 (Pubitemid 38268953)
97. Momparler RL, Bouffard DY, Momparler LF, et al. Pilot phase I-II study on 5-aza-2-deoxycytidine (Decitabine) in patients with metastatic lung cancer. Anticancer Drugs 1997;8(4):358-68 (Pubitemid 27204954)
98. Venturelli S, Berger A, Weiland T, et al. Differential induction of apoptosis and senescence by the DNA methyltransferase inhibitors 5-azacytidine and 5-aza-2- deoxycytidine in solid tumor cells. Mol Cancer Ther 2013;12(10):2226-36
99. Henning SM, Wang P, Carpenter CL, Heber D. Epigenetic effects of green tea polyphenols in cancer. Epigenomics 2013;5(6):729-41
100. Bieschke J. Natural compounds may open new routes to treatment of amyloid diseases. Neurotherapeutics 2013;10(3):429-39
101. Dragicevic N, Smith A, Lin X, et al. Green tea epigallocatechin-3-gallate (EGCG) and other flavonoids reduce Alzheimers amyloid-induced mitochondrial dysfunction. J Alzheimers Dis 2011;26(3):507-21
102. Zhang X, Wu M, Lu F, et al. Involvement of alpha7 nAChR signaling cascade in epigallocatechin gallate suppression of beta-amyloid-induced apoptotic cortical neuronal insults. Mol Neurobiol 20144;9(1):66-77
103. Mai A. Small-molecule chromatinmodifying agents: therapeutic applications. Epigenomics 2010;2(2):307-24
104. Cacabelos R. World guide for drug use and pharmacogenomics. EuroEspes Publishing; Corunna, Spain: 2012
105. Gagliano H, Delgado-Morales R, Sanz-Garcia A, Armario A. High doses of the histone deacetylase inhibitor sodium butyrate trigger a stress-like response. Neuropharmacology 2013;79C:75-82
106. Levenson JM, ORiordan KJ, Brown KD, et al. Regulation of histone acetylation during memory formation in the hippocampus. J Biol Chem 2004;279(39):40545-59 (Pubitemid 39287646)
107. Levenson JM, Sweatt JD. Epigenetic mechanisms in memory formation. Nat Rev Neurosci 2005;6(2):108-18 (Pubitemid 40188945)
108. Govindarajan N, Agis-Balboa RC, Walter J, et al. Sodium butyrate improves memory function in an Alzheimers disease mouse model when administered at an advanced stage of disease progression. J Alzheimers Dis 2011;26(1):187-97
109. Ricobaraza A, Cuadrado-Tejedor M, Marco S, et al. Phenylbutyrate rescues dendritic spine loss associated with memory deficits in a mouse model of Alzheimer disease. Hippocampus 2012;22(5):1040-50
110. Kilgore M, Miller CA, Fass DM, et al. Inhibitors of class 1 histone deacetylases reverse contextual memory deficits in a mouse model of Alzheimers disease. Neuropsychopharmacology 2010;35(4):870-80
111. Su Y, Ryder J, Li B, et al. Lithium, a common drug for bipolar disorder treatment, regulates amyloid-precursor protein processing. Biochemistry 2004;43(22):6899-908 (Pubitemid 38720508)
112. Qing H, He G, Ly PT, et al. Valproic acid inhibits Abeta production, neuritic plaque formation, and behavioral deficits in Alzheimers disease mouse models. J Exp Med 2008;205(12):2781-9
113. Vecsey CG, Hawk JD, Lattal KM, et al. Histone deacetylase inhibitors enhance memory and synaptic plasticity via CREB: CBP-dependent transcriptional activation. J Neurosci 2007;27(23):6128-40 (Pubitemid 46890024)
114. Nuutinen T, Suuronen T, Kauppinen A, Salminen A. Valproic acid stimulates clusterin expression in human astrocytes: implications for Alzheimers disease. Neurosci Lett 2010;475(2):64-8
115. Hanson JE, La H, Plise E, et al. SAHA enhances synaptic function and plasticity in vitro but has limited brain availability in vivo and does not impact cognition. PLoS One 2013;8(7):e69964
116. Lancelot J, Caby S, Dubois-Abdesselem F, et al. Schistosoma mansoni Sirtuins: characterization and potential as chemotherapeutic targets. PLoS Negl Trop Dis 2013;7(9):e2428
117. Aljada A, Dong L, Mousa SA. Sirtuin-targeting drugs: mechanisms of action and potential therapeutic applications. Curr Opin Investig Drugs 2010;11(10):1158-68
118. Granzotto A, Zatta P. Resveratrol acts not through anti-aggregative pathways but mainly via its scavenging properties against Abeta and Abeta-metal complexes toxicity. PLoS One 2011;6(6):e21565
119. Zhao YQ, Jordan IK, Lunyak VV. Epigenetics components of aging in the central nervous system. Neurotherapeutics 2013;10(4):647-63
120. Feng X, Liang N, Zhu D, et al. Resveratrol inhibits beta-amyloid-induced neuronal apoptosis through regulation of SIRT1-ROCK1 signaling pathway. PLoS One 2013;8(3):e59888
121. Green KN, Steffan JS, Martinez-Coria H, et al. Nicotinamide restores cognition in Alzheimers disease transgenic mice via a mechanism involving sirtuin inhibition and selective reduction of Thr231-phosphotau. J Neurosci 2008;28(45):11500-10
122. Trapp J, Meier R, Hongwiset D, et al. Structure-activity studies on suramin analogues as inhibitors of NAD+- dependent histone deacetylases (sirtuins). ChemMedChem 2007;2(10):1419-31
123. Haggarty SJ, Koeller KM, Wong JC, et al. Domain-selective small-molecule inhibitor of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation. Proc Natl Acad Sci USA 2003;100(8):4389-94 (Pubitemid 36457739)
124. Arrowsmith CH, Bountra C, Fish PV, et al. Epigenetic protein families: a new frontier for drug discovery. Nat Rev Drug Discov 2012;11(5):384-400
125. Yu CW, Chang PT, Hsin LW, et al. Quinazolin-4-one derivatives as selective histone deacetylase-6 inhibitors for the treatment of Alzheimers disease. J Med Chem 2013;56(17):6775-91
126. Hung SW, Mody H, Marrache S, et al. Pharmacological reversal of histone methylation presensitizes pancreatic cancer cells to nucleoside drugs: in vitro optimization and novel nanoparticle delivery studies. PLoS One 2013;8(8):e71196
127. Witkin JM, Li X. Curcumin, an active constiuent of the ancient medicinal herb Curcuma longa L.: some uses and the establishment and biological basis of medical efficacy. CNS Neurol Disord Drug Targets 2013;12(4):487-97
128. Sood PK, Nahar U, Nehru B. Curcumin attenuates aluminum-induced oxidative stress and mitochondrial dysfunction in rat brain. Neurotox Res 2011;20(4):351-61
129. Hoppe JB, Coradini K, Frozza RL, et al. Free and nanoencapsulated curcumin suppress beta-amyloid-induced cognitive impairments in rats: Involvement of BDNF and Akt/GSK-3beta signaling pathway. Neurobiol Learn Mem 2013;106:134-44
130. Ahmed T, Gilani AH. Therapeutic potential of turmeric in Alzheimers disease: curcumin or curcuminoids? Phytother Res 2013;28(4):517-25
131. Hishikawa N, Takahashi Y, Amakusa Y, et al. Effects of turmeric on Alzheimers disease with behavioral and psychological symptoms of dementia. Ayu 2012;33(4):499-504
132. Højfeldt JW, Agger K, Helin K. Histone lysine demethylases as targets for anticancer therapy. Nat Rev Drug Discov 2013;12(12):917-30
133. Zhang L, Zhang Y, Chou CJ, et al. Histone deacetylase inhibitors with enhanced enzymatic inhibition effects and potent in vitro and in vivo antitumor activities. ChemMedChem 2014;9(3):638-48
134. Cohen JE, Lee PR, Chen S, et al. MicroRNA regulation of homeostatic synaptic plasticity. Proc Natl Acad Sci USA 2011;108(28):11650-5
135. Chen S, Ge X, Chen Y, et al. Advances with RNA interference in Alzheimers disease research. Drug Des Devel Ther 2013;7:117-25
136. Li B, Sun H. MiR-26a promotes neurite outgrowth by repressing PTEN expression. Mol Med Rep 2013;8(2):676-80
137. Zhang Y, Yu Q, Lai TB, et al. Effects of small interfering RNA targeting sphingosine kinase-1 gene on the animal model of Alzheimers disease. J Huazhong Univ Sci Technolog Med Sci 2013;33(3):427-32
138. Ni J, Wang P, Zhang J, et al. Silencing of the P2X(7) receptor enhances amyloid-beta phagocytosis by microglia. Biochem Biophys Res Commun 2013;434(2):363-9
139. Varela MA, Roberts TC, Wood MJ. Epigenetics and ncRNAs in brain function and disease: mechanisms and prospects for therapy. Neurotherapeutics 2013;10(4):621-31
140. Picaud S, Wells C, Felletar I, et al. RVX- 208, an inhibitor of BET transcriptional regulators with selectivity for the second bromodomain. Proc Natl Acad Sci USA 2013;110(49):19754-9
141. Martin SL, Hardy TM, Tollefsbol TO. Medicinal chemistry of the epigenetic diet and caloric restriction. Curr Med Chem 2013;20(32):4050-9
142. Fuso A, Nicolia V, Cavallaro RA, Scarpa S. DNA methylase and demethylase activities are modulated by one-carbon metabolism in Alzheimers disease models. J Nutr Biochem 2011;22(3):242-51
143. Trasler J, Deng L, Melnyk S, et al. Impact of Dnmt1 deficiency, with and without low folate diets, on tumor numbers and DNA methylation in Min mice. Carcinogenesis 2003;24(1):39-45 (Pubitemid 36196727)
144. Coppedè F. Advances in the genetics and epigenetics of neurodegenerative diseases. EPINEUD 2013;1:2-30
145. Wang SC, Oelze B, Schumacher A. Age-specific epigenetic drift in late-onset Alzheimers disease. PLoS One 2008;3(7):e2698
146. Cacabelos R, Takeda M. Pharmacogenomics, nutrigenomics and future therapeutics in Alzheimers disease. Drugs Future 2006;31(Suppl B):5-146
147. Cacabelos R. Role of nutrition in the prevention of Alzheimers disease. Aging Health 2005;1(3):359-62
148. Bordone L, Guarente L. Calorie restriction, SIRT1 and metabolism: understanding longevity. Nat Rev Mol Cell Biol 2005;6(4):298-305 (Pubitemid 40516896)
149. Dauncey MJ. Genomic and epigenomic insights into nutrition and brain disorders. Nutrients 2013;5(3):887-914
150. Kim IW, Han N, Burckart GJ, Oh JM. Epigenetic changes in gene expression for drug-metabolizing enzymes and transporters. Pharmacotherapy 2014;34(2):140-50
151. Cacabelos R. The metabolomics paradigm of pharmacogenomics in complex disorders. Metabolomics 2012;2:e119
152. Oda S, Fukami T, Yokoi T, Nakajima M. Epigenetic regulation of the tissue-specific expression of human UDP-glucuronosyltransferase (UGT) 1A10. Biochem Pharmacol 2014;87(4):660-7
153. Kang H, Kim C, Lee H, et al. Post-transcriptional controls by ribonucleoprotein complexes in the acquisition of drug resistance. Int J Mol Sci 2013;14(8):17204-20
154. Williams KE, Anderton DL, Lee MP, et al. High-density array analysis of DNA methylation in tamoxifen-resistant breast cancer cell lines. Epigenetics 2014;9(2):297-307
155. Grimminger T, Pernhorst K, Surges R, et al. Levetiracetam resistance: synaptic signatures & corresponding promoter SNPs in epileptic hippocampi. Neurobiol Dis 2013;60:115-25
156. Réus GZ, Abelaira HM, Dos Santos MA, et al. Ketamine and imipramine in the nucleus accumbens regulate histone deacetylation induced by maternal deprivation and are critical for associated behaviors. Behav Brain Res 2013;256:451-6
157. Powell TR, Smith RG, Hackinger S, et al. DNA methylation in interleukin-11 predicts clinical response to antidepressants in GENDEP. Transl Psychiatry 2013;3:e300
158. Schroeder FA, Lewis MC, Fass DM, et al. A selective HDAC 1/2 inhibitor modulates chromatin and gene expression in brain and alters mouse behavior in two mood-related tests. PLoS One 2013;8(8):e71323
159. Cacabelos R, Torrellas C, López-Muñoz F. Epigenomics of Alzheimers disease. J Exper Clin Med 2014.DOI: 10.1016/j.jecm.2014.03.010
160. Cacabelos R. Donepezil in Alzheimers disease: from conventional trials to pharmacogenetics. Neuropsychiatr Dis Treat 2007;3(3):303-33 (Pubitemid 47215008)
161. Brahe C, Vitali T, Tiziano FD, et al. Phenylbutyrate increases SMN gene expression in spinal muscular atrophy patients. Eur J Hum Genet 2005;13(2):256-9 (Pubitemid 40220572)
162. Marks PA, Xu WS. Histone deacetylase inhibitors: potential in cancer therapy. J Cell Biochem 2009;107(4):600-8
163. Marks PA. The clinical development of histone deacetylase inhibitors as targeted anticancer drugs. Expert Opin Investig Drugs 2010;19(9):1049-66
164. Salminen A, Tapiola T, Korhonen P, Suuronen T. Neuronal apoptosis induced by histone deacetylase inhibitors. Mol Brain Res 1998;61(1-2):203-6 (Pubitemid 28511364)
165. Kelly-Sell MJ, Kim YH, Straus S, et al. The histone deacetylase inhibitor, romidepsin, suppresses cellular immune functions of cutaneous T-cell lymphoma patients. Am J Hematol 2012;87(4):354-60
166. Rossi LE, Avila DE, Spallanzani RG, et al. Histone deacetylase inhibitors impair NK cell viability and effector functions through inhibition of activation and receptor expression. J Leukoc Biol 2012;91(2):321-31
167. Alvarez-Erviti L, Seow Y, Yin H, et al. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol 2011;29(4):341-5
168. Lakhal S, Andaloussi SE, OLoughlin AJ, et al. RNAi therapeutic delivery by exosomes. In: Howard KN, editor. RNA interference from biology to therapeutics. Spriger; London, UK: 2013. p. 185-207
169. Kuhn DE, Nuovo GJ, Terry AV Jr, et al. Chromosome 21-derived microRNAs provide an etiological basis for aberrant protein expression in human Down syndrome brains. J Biol Chem 2013;288(6):4228
170. Junn E, Mouradian MM. MicroRNAs in neurodegenerative diseases and their therapeutic potential. Pharmacol Ther 2012;133(2):142-50
171. Gonzales-Roybal G, Lim DA. Chromatin-based epigenetics of adult subventricular zone neural stem cells. Front Genet 2013;4:194
172. Kar S, Parbin S, Deb M, et al. Epigenetic choreography of stem cells: the DNA demethylation episode of development. Cell Mol Life Sci 2014;71(6):1017-32
173. Yang H, Xie Z, Wei L, et al. Human umbilical cord mesenchymal stem cellderived neuron-like cells rescue memory deficits and reduce amyloid-beta deposition in an AbetaPP/PS1 transgenic mouse model. Stem Cell Res Ther 2013;4(4):76
174. Szyf M, Bick J. DNA methylation: a mechanism for embedding early life experiences in the genome. Child Dev 2013;84(1):49-57