Modulating alzheimer's disease through caffeine: A putative link to epigenetics

Journal of Alzheimer's Disease

Volumn 24, Issue SUPPL. 2, 2011, Pages 161-171

  Marques, Sueli ^a,b,c   Lopes, Luísa Vaqueiro ^b  

^a INSTITUTO DE MEDICINA MOLECULAR   (Portugal)

^b INSTITUTO DE MEDICINA MOLECULAR   (Portugal)

^c UNIVERSITY MEDICAL CENTER GÖTTINGEN   (Germany)

Author keywords

Adenosine A2A receptors; aging; Alzheimer's disease; caffeine; epigenetics

Indexed keywords

5,10 METHYLENETETRAHYDROFOLATE REDUCTASE (FADH2); ADENOSINE A1 RECEPTOR; ADENOSINE A2A RECEPTOR; ADENOSINE A2A RECEPTOR ANTAGONIST; ALPHA 2 MACROGLOBULIN; AMYLOID PRECURSOR PROTEIN; APOLIPOPROTEIN E; CAFFEINE; DIPEPTIDYL CARBOXYPEPTIDASE; DNA METHYLTRANSFERASE 1; INSULINASE; PRESENILIN 1; PRESENILIN 2;

AGING; ALZHEIMER DISEASE; DIETARY INTAKE; DISEASE COURSE; DRUG EFFICACY; DRUG MECHANISM; DRUG TARGETING; ENVIRONMENTAL FACTOR; EPIGENETICS; GENE EXPRESSION; GENETIC VARIABILITY; HUMAN; NONHUMAN; PARKINSON DISEASE; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW;

EID: 79955649058     PISSN: 13872877     EISSN: None     Source Type: Journal    
DOI: 10.3233/JAD-2011-110032     Document Type: Review

References (102)

1. Alzheimer's Association (2010) 2010 Alzheimer's disease facts and figures. Alzheimers Dement 6, 158-194.
2. LaFerla FM, Oddo S (2005) Alzheimer's disease: Abeta, tau and synaptic dysfunction. Trends Mol Med 11, 170-176.
3. Selkoe DJ (2001) Alzheimer's disease: genes, proteins, and therapy. Physiol Rev 81, 741-766. (Pubitemid 32267077)
4. Mudher A, Lovestone S (2002) Alzheimer's disease-do tauists and baptists finally shake hands? Trends Neurosci 25, 22-26. (Pubitemid 34093781)
5. Shastry BS (2003) Neurodegenerative disorders of protein aggregation. Neurochem Int 43, 1-7. (Pubitemid 36246521)
6. Goedert M, Spillantini MG (2006) A century of Alzheimer's disease. Science 314, 777-781. (Pubitemid 44706636)
7. Price JL, Morris JC (1999) Tangles and plaques in nondemented aging and "preclinical" Alzheimer's disease. Ann Neurol 45, 358-368. (Pubitemid 29120041)
8. Oddo S, Caccamo A, Kitazawa M, Tseng BP, LaFerla FM (2003) Amyloid deposition precedes tangle formation in a triple transgenic model of Alzheimer's disease. Neurobiol Aging24, 1063-1070. (Pubitemid 37487883)
9. St George-Hyslop PH, Petit A (2005) Molecular biology and genetics of Alzheimer's disease. C R Biol 328, 119-130. (Pubitemid 40247057)
10. Sorbi S, Forleo P, Tedde A, Cellini E, Ciantelli M, Bagnoli S, Nacmias B (2001) Genetic risk factors in familial Alzheimer's disease. Mech Ageing Dev 122, 1951-1960. (Pubitemid 32925105)
11. Seripa D, Panza F, Franceschi M, D'Onofrio G, Solfrizzi V, Dallapiccola B, Pilotto A (2009) Non-apolipoprotein E and apolipoprotein E genetics of sporadic Alzheimer's disease. Ageing Res Rev 8, 214-236.
12. Tanzi RE, Bertram L (2001) New frontiers in Alzheimer's disease genetics. Neuron 32, 181-184. (Pubitemid 33030187)
13. Rocchi A, Pellegrini S, Siciliano G, Murri L (2003) Causative and susceptibility genes for Alzheimer's disease: a review. Brain Res Bull 61, 1-24. (Pubitemid 36682979)
14. Stozicka Z, Zilka N, Novak M (2007) Risk and protective factors for sporadic Alzheimer's disease. Acta Virol 51, 205222.
15. Feinberg AP (2007) Phenotypic plasticity and the epigenetics of human disease. Nature 447, 433-440. (Pubitemid 46816750)
16. Serrano F, Klann E (2004) Reactive oxygen species and synaptic plasticity in the aging hippocampus. Ageing Res Rev 3, 431-443. (Pubitemid 39487899)
17. Ames BN (2004) Mitochondrial decay, a major cause of aging, canbe delayed. J Alzheimers Dis 6, 117-121. (Pubitemid 38560246)
18. Lu T, Pan Y, Kao SY, Li C, Kohane I, Chan J, Yankner BA (2004) Gene regulation and DNA damage in the ageing human brain. Nature 429, 883-891. (Pubitemid 38843301)
19. Mattson MP, Magnus T (2006) Ageing and neuronal vulnerability. Nat Rev Neurosci 7, 278-294.
20. Petot GJ, Friedland RP (2004) Lipids, diet and Alzheimer disease: an extended summary. J Neurol Sci 226, 31-33. (Pubitemid 39505401)
21. Luchsinger JA, Noble JM, Scarmeas N (2007) Diet and Alzheimer's disease. Curr Neurol Neurosci Rep 7, 366-372. (Pubitemid 47422777)
22. Luchsinger JA, Tang MX, Siddiqui M, Shea S, Mayeux R (2004) Alcohol intake and risk of dementia. J Am Geriatr Soc 52, 540-546. (Pubitemid 38480630)
23. Harwood DG, Kalechstein A, Barker WW, Strauman S, St George-Hyslop P, Iglesias C, Loewenstein D, Duara R (2010) The effect of alcohol and tobacco consumption, and apolipoprotein E genotype, on the age of onset in Alzheimer's disease. Int J Geriatr Psychiatry 25, 511-518.
24. de Mendonca A, Cunha RA (2010) Therapeutic oppor-tunities for caffeine in Alzheimer's disease and other neurodegenerative disorders. J Alzheimers Dis 20 (Suppl 1), S1-S2.
25. Carter AJ, O'Connor WT, Carter MJ, Ungerstedt U (1995) Caffeine enhances acetylcholine release in the hippocam-pus in vivo by a selective interaction with adenosine A1 receptors. J Pharmacol Exp Ther 273, 637-642.
26. Arendash GW, Schleif W, Rezai-Zadeh K, Jackson EK, Zacharia LC, Cracchiolo JR, Shippy D, Tan J (2006) Caffeine protects Alzheimer's mice against cognitive impairment and reduces brain beta-amyloid production. Neuroscience 142, 941-952. (Pubitemid 44740473)
27. Dall'Igna OP, Fett P, Gomes MW, Souza DO, Cunha RA, Lara DR (2007) Caffeine and adenosine A(2a) receptor antagonists prevent beta-amyloid (25-35)-induced cogni-tive deficits in mice. Exp Neurol 203, 241-245. (Pubitemid 44821181)
28. Maia L, de Mendonca A (2002) Does caffeine intake protect from Alzheimer's disease? Eur JNeurol 9, 377-382. (Pubitemid 35013893)
29. Lindsay J, Laurin D, Verreault R, Hebert R, Helliwell B, Hill GB, McDowell I (2002) Risk factors for Alzheimer's disease: a prospective analysis from the Canadian Study of Health and Aging. Am J Epidemiol 156, 445-453. (Pubitemid 34976983)
30. Tyas SL, Manfreda J, Strain LA, Montgomery PR (2001) Risk factors for Alzheimer's disease: a population-based, longitudinal study in Manitoba, Canada. Int J Epidemiol 30, 590-597. (Pubitemid 32600256)
31. van Boxtel MP, Schmitt JA, Bosma H, Jolles J (2003) The effects of habitual caffeine use on cognitive change: a longitudinal perspective. Pharmacol Biochem Behav 75, 921-927. (Pubitemid 37289479)
32. Johnson-Kozlow M, Kritz-Silverstein D, Barrett-Connor E, Morton D (2002) Coffee consumption and cognitive func-tion among older adults. Am J Epidemiol 156, 842-850. (Pubitemid 35215765)
33. Rosso A, Mossey J, Lippa CF (2008) Caffeine: neuropro-tective functions in cognition and Alzheimer's disease. Am JAlzheimers Dis Other Demen 23, 417-422.
34. Fredholm BB, Battig K, Holmen J, Nehlig A, Zvartau EE (1999) Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacol Rev 51, 83-133. (Pubitemid 29113867)
35. Linden J (2001) Molecular approach to adenosine receptors: receptor-mediated mechanisms of tissue protection. Annu Rev Pharmacol Toxicol 41, 775-787. (Pubitemid 32385906)
36. Ribeiro JA, Sebastiao AM (2010) Modulation and meta-modulation of synapses by adenosine. Acta Physiol (Oxf) 199, 161-169.
37. Sebastiao AM, Ribeiro JA (2009) Tuning and fine-tuning of synapses with adenosine. Curr Neuropharmacol 7, 180-194.
38. Gomes CV, Kaster MP, Tome AR, Agostinho PM, Cunha RA (2010) Adenosine receptors and brain diseases: neuro-protection and neurodegeneration. Biochim Biophys Acta, doi:10.1016/j.bbamem.2010.12.001
39. Sawyer DA, Julia HL, Turin AC (1982) Caffeine and human behavior: arousal, anxiety, and performance effects. JBehav Med5, 415-439. (Pubitemid 13192393)
40. Costenla AR, Cunha RA, de Mendonca A (2010) Caffeine, adenosine receptors, and synaptic plasticity. J Alzheimers Dis 20 (Suppl 1), S25-S34.
41. Rahman A (2009) The role of adenosine in Alzheimer's disease. Curr Neuropharmacol 7, 207-216.
42. Ritchie K, Carriere I, de Mendonca A, Portet F, Dartigues JF, Rouaud O, Barberger-Gateau P, Ancelin ML (2007) The neuroprotective effects of caffeine: a prospective pop-ulation study (the Three City Study). Neurology 69, 536-545. (Pubitemid 47357260)
43. Corley J, Jia X, Kyle JA, Gow AJ, Brett CE, Starr JM, McNeill G, Deary IJ (2010) Caffeine consumption and cog-nitive function at age 70: the Lothian Birth Cohort 1936 study. Psychosom Med 72, 206-214.
44. Santos C, Lunet N, Azevedo A, de Mendonca A, Ritchie K, Barros H (2010) Caffeine intake is associated with a lower risk of cognitive decline: a cohort study from Portugal. J Alzheimers Dis 20 (Suppl 1), S175-S185.
45. Santos C, Costa J, Santos J, Vaz-Carneiro A, Lunet N (2010) Caffeine intake and dementia: systematic review and meta-analysis. J Alzheimers Dis 20 (Suppl 1), S187-S204.
46. Eskelinen MH, Kivipelto M (2010) Caffeine as a protective factor in dementia and Alzheimer's disease. J Alzheimers Dis 20 (Suppl 1), S167-174.
47. Cao C, Cirrito JR, Lin X, Wang L, Verges DK, Dickson A, Mamcarz M, Zhang C, Mori T, Arendash GW, Holtzman DM, Potter H (2009) Caffeine suppresses amyloid-beta lev-els in plasma and brain of Alzheimer's disease transgenic mice. J Alzheimers Dis 17, 681-697.
48. Prediger RD, Batista LC, Takahashi RN (2005) Caffeine reverses age-related deficits in olfactory discrimination and social recognition memory in rats. Involvement of adeno-sine A1 and A2A receptors. Neurobiol Aging 26, 957-964. (Pubitemid 40249499)
49. Costa MS, Botton PH, Mioranzza S, Souza DO, Porciuncula LO (2008) Caffeine prevents age-associated recognition memory decline and changes brain-derived neurotrophic factor and tirosine kinase receptor (TrkB) content in mice. Neuroscience 153, 1071-1078.
50. Riksen NP, Rongen GA, Smits P (2009) Acute and long-term cardiovascular effects of coffee: implications for coronary heart disease. Pharmacol Ther 121, 185-191.
51. Daly JW (2007) Caffeine analogs: biomedical impact. Cell Mol Life Sci 64, 2153-2169. (Pubitemid 350092417)
52. Canas PM, Porciuncula LO, Cunha GM, Silva CG, Machado NJ, Oliveira JM, Oliveira CR, Cunha RA (2009) Adenosine A2A receptor blockade prevents synaptotoxicity and mem-ory dysfunction caused by beta-amyloid peptides via p38 mitogen-activated protein kinase pathway. J Neurosci 29, 14741-14751.
53. Cunha GM, Canas PM, Oliveira CR, Cunha RA (2006) Increased density and synapto-protective effect of adenosine A2A receptors upon sub-chronic restraint stress. Neuro-science 141, 1775-1781. (Pubitemid 44233132)
54. Cunha RA (2005) Neuroprotection by adenosine in the brain: from A(1) receptor activation to A(2A) receptor blockade. Purinergic Signal 1, 111-134. (Pubitemid 40466898)
55. Bruns RF, Lu GH, Pugsley TA (1986) Characterization ofthe A2 adenosine receptor labeled by [3H]NECA in rat striatal membranes. Mol Pharmacol 29, 331-346. (Pubitemid 16078480)
56. Brown SJ, James S, Reddington M, Richardson PJ (1990) Both A1 and A2a purine receptors regulate striatal acetyl-choline release. J Neurochem 55, 31-38.
57. Schwarzschild MA, Agnati L, Fuxe K, Chen JF, Morelli M (2006) Targeting adenosine A2A receptors in Parkinson's disease. Trends Neurosci 29, 647-654. (Pubitemid 44602262)
58. Kalda A, Yu L, Oztas E, Chen JF (2006) Novel neuroprotec-tion by caffeine and adenosine A(2A) receptor antagonists in animal models of Parkinson's disease. J Neurol Sci 248, 9-15. (Pubitemid 44647288)
59. Xu K, Bastia E, Schwarzschild M (2005) Therapeutic poten-tial of adenosine A(2A) receptor antagonists in Parkinson's disease. Pharmacol Ther 105, 267-310. (Pubitemid 40297894)
60. Morelli M, Di Paolo T, Wardas J, Calon F, Xiao D, Schwarzschild MA (2007) Role of adenosine A2A recep-tors in parkinsonian motor impairment and l-DOPA-induced motor complications. Prog Neurobiol 83, 293-309. (Pubitemid 350102747)
61. Pinna A (2009) Novel investigational adenosine A2A recep-tor antagonists for Parkinson's disease. Expert Opin Investig Drugs 18, 1619-1631.
62. Sebastiao AM, Ribeiro JA (1992) Evidence for the presence of excitatory A2 adenosine receptors in the rat hippocampus. Neurosci Lett 138, 41-44.
63. Rodrigues RJ, Canas PM, Lopes LV, Oliveira CR, Cunha RA (2008) Modification of adenosine modulation of acetyl-choline release in the hippocampus of aged rats. Neurobiol Aging29, 1597-1601.
64. Cunha RA, Johansson B, van der Ploeg I, Sebastiao AM, Ribeiro JA, Fredholm BB (1994) Evidence for functionally important adenosine A2 a receptors in the rat hippocampus. Brain Res 649, 208-216. (Pubitemid 24197214)
65. Cunha RA, Constantino MC, Sebastiao AM, Ribeiro JA (1995) Modification ofA1 and A2aadenosinereceptorbind-ing in aged striatum, hippocampus and cortex of the rat. Neuroreport 6, 1583-1588.
66. Lopes LV, Cunha RA, Kull B, Fredholm BB, Ribeiro JA (2002) Adenosine A(2A) receptor facilitation of hippocam-pal synaptic transmission is dependent on tonic A(1) receptor inhibition. Neuroscience 112, 319-329. (Pubitemid 34607016)
67. Lopes LV, Cunha RA, Ribeiro JA (1999) Cross talk between A(1) and A(2A) adenosine receptors in the hippocampus and cortex of young adult and old rats. J Neurophysiol 82, 3196-3203. (Pubitemid 30017446)
68. Rebola N, Sebastiao AM, de Mendonca A, Oliveira CR, Ribeiro JA, Cunha RA (2003) Enhanced adenosine A2A receptor facilitation of synaptic transmission in the hip-pocampus of agedrats. J Neurophysiol 90, 1295-1303. (Pubitemid 37092606)
69. Angulo E, Casado V, Mallol J, Canela EI, Vinals F, Fer-rer I, Lluis C, Franco R (2003) A1 adenosine receptors accumulate in neurodegenerative structures in Alzheimer disease and mediate both amyloid precursor protein pro-cessing and tau phosphorylation and translocation. Brain Pathol 13, 440-451. (Pubitemid 37420689)
70. Albasanz JL, Perez S, Barrachina M, Ferrer I, Martin M (2008) Up-regulation of adenosine receptors in the frontal cortex in Alzheimer's disease. Brain Pathol 18, 211-219. (Pubitemid 351430397)
71. Cognato GP, Agostinho PM, Hockemeyer J, Muller CE, Souza DO, Cunha RA (2010) Caffeine and an adeno-sine A(2A) receptor antagonist prevent memory impairment and synaptotoxicity in adult rats triggered by a convulsive episode in early life. J Neurochem 112, 453-462.
72. Cornelis MC, El-Sohemy A, Campos H (2007) Genetic polymorphism of the adenosine A2A receptor is associ-ated with habitual caffeine consumption. Am J Clin Nutr 86, 240-244. (Pubitemid 47041616)
73. Childs E, Hohoff C, Deckert J, Xu K, Badner J, de Wit H (2008) Association between ADORA2A and DRD2 polymorphisms and caffeine-induced anxiety. Neuropsy-chopharmacology 33, 2791-2800.
74. Hamilton SP, Slager SL, De Leon AB, Heiman GA, Klein DF, Hodge SE, Weissman MM, Fyer AJ, Knowles JA (2004) Evidence for genetic linkage between a polymorphism in the adenosine 2A receptor and panic disorder. Neuropsy-chopharmacology 29, 558-565. (Pubitemid 38365933)
75. Dhaenens CM, Burnouf S, Simonin C, Van Brussel E, Duhamel A, Defebvre L, Duru C, Vuillaume I, Cazeneuve C, Charles P, Maison P, Debruxelles S, Verny C, Gervais H, Azulay JP, Tranchant C, Bachoud-Levi AC, Durr A, Buee L, Krystkowiak P, Sablonniere B, Blum D (2009) A genetic variation in the ADORA2A gene modifies age at onset in Huntington's disease. Neurobiol Dis 35, 474-476.
76. Hohoff C, Mullings EL, Heatherley SV, Freitag CM, Neu-mann LC, Domschke K, Krakowitzky P, Rothermundt M, Keck ME, Erhardt A, Unschuld PG, Jacob C, Fritze J, Ban-delow B, Maier W, Holsboer F, Rogers PJ, Deckert J (2010) Adenosine A(2A) receptor gene: evidence for association of risk variants with panic disorder and anxious personality. J Psychiatr Res 44, 930-937.
77. Taherzadeh-Fard E, Saft C, Wieczorek S, Epplen JT, Arning L (2010) Age at onset in Huntington's disease: replication studyontheassociations of ADORA2A, HAP1 andOGG1. Neurogenetics 11, 435-439.
78. Lopes LV, Sebastião AM, Ribeiro JA (2010) Adenosine and related drugs in brain diseases: present and future in clinical trials. Curr Top Med Chem, in press.
79. Jiang YH, Bressler J, Beaudet AL (2004) Epigenetics and human disease. Annu Rev Genomics Hum Genet 5, 479-510. (Pubitemid 39362754)
80. Dolinoy DC, Jirtle RL (2008) Environmental epigenomics in human health and disease. Environ Mol Mutagen 49, 4-8. (Pubitemid 351293007)
81. Fraga MF, Esteller M (2007) Epigenetics and aging: the targets and the marks. Trends Genet 23, 413-418. (Pubitemid 47088010)
82. Richardson B (2003) Impact of aging on DNA methylation. Ageing Res Rev 2, 245-261. (Pubitemid 38340315)
83. Tohgi H, Utsugisawa K, Nagane Y, Yoshimura M, Genda Y, Ukitsu M (1999) Reduction with age in methylcytosine in the promoter region\224 approximately\101 of the amyloid precursor protein gene in autopsy human cortex. Brain Res Mol Brain Res 70, 288-292. (Pubitemid 29317643)
84. Mastroeni D, McKee A, Grover A, Rogers J, Coleman PD (2009) Epigenetic differences in cortical neurons from a pair of monozygotic twins discordant for Alzheimer's disease. PLoS One 4, e 6617.
85. Wang SC, Oelze B, Schumacher A (2008) Age-specific epi-genetic drift in late-onset Alzheimer's disease. PLoS One 3, e 2698.
86. Ishii T, Hashimoto E, Ukai W, Tateno M, Yoshinaga T, Ono T, Watanabe K, Saito S, Saito T (2008) Epigenetic regulation in alcohol-related brain damage. Nihon Arukoru Yakubutsu Igakkai Zasshi 43, 705-713.
87. Shukla SD, Velazquez J, French SW, Lu SC, Ticku MK, Zakhari S (2008) Emerging role of epigenetics in the actions of alcohol. Alcohol Clin Exp Res 32, 1525-1534.
88. Slattery ML, Wolff RK, Herrick JS, Curtin K, Caan BJ, Samowitz W (2010) Alcohol consumption and rectal tumor mutations and epigenetic changes. Dis Colon Rectum 53, 1182-1189.
89. Ordovas JM, Smith CE (2010) Epigenetics and cardiovas-cular disease. Nat Rev Cardiol 7, 510-519.
90. Turunen MP, Aavik E, Yla-Herttuala S (2009) Epigenetics and atherosclerosis. Biochim Biophys Acta 1790, 886-891.
91. Fabiani E, Mitro N, Ilardi F, Almozzi A, Caruso D, Crestani M (2010) When food meets man: the contribution of epige-netics to health. Nutrients 2, 551-571.
92. Tollefsbol TO, Li Y (2010) Dietary effect on epigenetics during the aging process: In Epigenetics of Aging, Tollefsbol TO, ed. Springer, New York, pp. 407-416.
93. Mastroeni D, Grover A, Delvaux E, Whiteside C, Coleman PD, Rogers J (2010) Epigenetic changes in Alzheimer's disease: decrements in DNA methylation. Neurobiol Aging 31, 2025-2037.
94. Mattson MP, Shea TB (2003) Folate and homocysteine metabolism in neural plasticity and neurodegenerative dis-orders. Trends Neurosci 26, 137-146. (Pubitemid 36183675)
95. Quadri P, Fragiacomo C, Pezzati R, Zanda E, Forloni G, Tettamanti M, Lucca U (2004) Homocysteine, folate, and vitamin B-12 in mild cognitive impairment, Alzheimer dis-ease, and vascular dementia. Am J Clin Nutr 80, 114-122. (Pubitemid 41115564)
96. Bottiglieri T, Godfrey P, Flynn T, Carney MW, Toone BK, Reynolds EH (1990) Cerebrospinal fluid S-adenosy-lmethionine in depression and dementia: effects of treat-ment with parenteral and oral S-adenosylmethionine. J Neurol Neurosurg Psychiatry 53, 1096-1098.
97. Kennedy BP, Bottiglieri T, Arning E, Ziegler MG, Hansen LA, Masliah E (2004) Elevated S-adenosylhomocysteine in Alzheimer brain: influence on methyltransferases and cog-nitive function. J Neural Transm 111, 547-567. (Pubitemid 38478922)
98. Fuso A, Seminara L, Cavallaro RA, D'Anselmi F, Scarpa S (2005) S-adenosylmethionine/homocysteine cycle alterations modify DNA methylation status with consequent deregulation of PS1 and BACE and beta-amyloid produc-tion. Mol Cell Neurosci 28, 195-204. (Pubitemid 39656023)
99. Fuso A, Cavallaro RA, Zampelli A, D'Anselmi F, Piscopo P, Confaloni A, Scarpa S (2007) gamma-Secretase is differ-entially modulated by alterations of homocysteine cycle in neuroblastoma and glioblastoma cells. J Alzheimers Dis 11, 275-290. (Pubitemid 47094027)
100. Buira SP, Albasanz JL, Dentesano G, Moreno J, Martin M, Ferrer I, Barrachina M (2010) DNA methylation regulates adenosine A(2A) receptor cell surface expression levels. J Neurochem 112, 1273-1285.
101. Buira SP, Dentesano G, Albasanz JL, Moreno J, Martin M, Ferrer I, Barrachina M (2010) DNA methylation and Yin Yang-1 repress adenosine A2A receptor levels in human brain. J Neurochem 115, 283-295.
102. Marques SC, Oliveira CR, Pereira CM, Outeiro TF (2010) Epigenetics in neurodegeneration: A new layer of complexity. Prog Neuropsychopharmacol Biol Psychiatry, doi:10.1016/j.pnpbp.2010.08.008