Functional & Integrative Genomics

, Volume 11, Issue 4, pp 523–537 | Cite as

Emerging roles of epigenetic mechanisms in Parkinson’s disease



Epigenetic mechanisms have emerged as important components of a variety of human diseases, including cancer and central nervous system disorders. Despite recent studies highlighting the role of epigenetic mechanisms in several neurodegenerative and neuropsychiatric disorders, to date, there has been a paucity of studies exploring the role of epigenetic factors in Parkinson’s disease (PD). PD is a progressive neurological disorder with characteristic motor and non-motor symptoms, including a range of neuropsychiatric features, for which neither preventative nor effective long-term treatment strategies are available. It is one of the most common neurodegenerative disorders and the second most prevalent after Alzheimer’s disease. In this review, we present several lines of evidence suggesting that epigenetic factors may play an important role in the pathogenesis of PD and propose on this basis a framework to guide future investigations into epigenetic mechanisms and systems biology of PD. These notions, together with technical advances in the ability to perform genome-wide analysis of epigenomic states, and newly available small-molecule probes targeting chromatin-modifying enzymes, may help design new treatment strategies for PD and other human diseases involving epigenetic dysregulation.


Parkinson’s disease Epigenetics Neurodegenerative disorders Neurodevelopmental disorders Psychiatric disorders Systems biology 



Part of this project has been funded by Iran National Science Foundation ( S.J.H. is supported by Award Number R01DA028301 from the National Institute On Drug Abuse. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute On Drug Abuse or the National Institutes of Health.


  1. Abdolmaleky HM, Zhou JR, Thiagalingam S, Smith CL (2008) Epigenetic and pharmacoepigenomic studies of major psychoses and potentials for therapeutics. Pharmacogenomics 9(12):1809–1823. doi: 10.2217/14622416.9.12.1809 PubMedCrossRefGoogle Scholar
  2. Abel T, Zukin RS (2008) Epigenetic targets of HDAC inhibition in neurodegenerative and psychiatric disorders. Curr Opin Pharmacol 8(1):57–64. doi: 10.1016/j.coph.2007.12.002 PubMedCrossRefGoogle Scholar
  3. Adamczyk A, Kazmierczak A (2009) Alpha-synuclein inhibits poly (ADP-ribose) polymerase-1 (PARP-1) activity via NO-dependent pathway. Folia Neuropathol 47(3):247–251PubMedGoogle Scholar
  4. Alarcon JM, Malleret G, Touzani K, Vronskaya S, Ishii S, Kandel ER, Barco A (2004) Chromatin acetylation, memory, and LTP are impaired in CBP+/− mice: a model for the cognitive deficit in Rubinstein–Taybi syndrome and its amelioration. Neuron 42(6):947–959. doi: 10.1016/j.neuron.2004.05.021 PubMedCrossRefGoogle Scholar
  5. Allis CD, Jenuwein T, Reinberg D (2007) Epigenetics, 1st edn. Cold Spring Harbor Laboratory Press, New YorkGoogle Scholar
  6. Alvarez-Gonzalez R (2007) Genomic maintenance: the p53 poly(ADP-ribosyl)ation connection. Sci STKE 2007(415):pe68. doi: 10.1126/stke.4152007pe68 PubMedCrossRefGoogle Scholar
  7. Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY (1999) Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet 23(2):185–188. doi: 10.1038/13810 PubMedCrossRefGoogle Scholar
  8. Arguelles S, Herrera AJ, Carreno-Muller E, de Pablos RM, Villaran RF, Espinosa-Oliva AM, Machado A, Cano J (2010) Degeneration of dopaminergic neurons induced by thrombin injection in the substantia nigra of the rat is enhanced by dexamethasone: role of monoamine oxidase enzyme. Neurotoxicology 31(1):55–66. doi: 10.1016/j.neuro.2009.12.001 PubMedCrossRefGoogle Scholar
  9. Bannon MJ, Michelhaugh SK, Wang J, Sacchetti P (2001) The human dopamine transporter gene: gene organization, transcriptional regulation, and potential involvement in neuropsychiatric disorders. Eur Neuropsychopharmacol 11(6):449–455PubMedCrossRefGoogle Scholar
  10. Bannon MJ, Pruetz B, Manning-Bog AB, Whitty CJ, Michelhaugh SK, Sacchetti P, Granneman JG, Mash DC, Schmidt CJ (2002) Decreased expression of the transcription factor NURR1 in dopamine neurons of cocaine abusers. Proc Natl Acad Sci USA 99(9):6382–6385. doi: 10.1073/pnas.092654299 PubMedCrossRefGoogle Scholar
  11. Barrachina M, Ferrer I (2009) DNA methylation of Alzheimer disease and tauopathy-related genes in postmortem brain. J Neuropathol Exp Neurol 68(8):880–891. doi: 10.1097/NEN.0b013e3181af2e46 PubMedCrossRefGoogle Scholar
  12. Bartholdi D, Roelfsema JH, Papadia F, Breuning MH, Niedrist D, Hennekam RC, Schinzel A, Peters DJ (2007) Genetic heterogeneity in Rubinstein-Taybi syndrome: delineation of the phenotype of the first patients carrying mutations in EP300. J Med Genet 44(5):327–333. doi: 10.1136/jmg.2006.046698 PubMedCrossRefGoogle Scholar
  13. Belyaev ND, Nalivaeva NN, Makova NZ, Turner AJ (2009) Neprilysin gene expression requires binding of the amyloid precursor protein intracellular domain to its promoter: implications for Alzheimer disease. EMBO Rep 10(1):94–100. doi: 10.1038/embor.2008.222 PubMedCrossRefGoogle Scholar
  14. Berger SL (2002) Histone modifications in transcriptional regulation. Curr Opin Genet Dev 12(2):142–148PubMedCrossRefGoogle Scholar
  15. Bird A (2007) Perceptions of epigenetics. Nature 447(7143):396–398. doi: 10.1038/nature05913 PubMedCrossRefGoogle Scholar
  16. Bossy-Wetzel E, Schwarzenbacher R, Lipton SA (2004) Molecular pathways to neurodegeneration. Nat Med 10(Suppl):S2–S9. doi: 10.1038/nm1067 PubMedCrossRefGoogle Scholar
  17. Brandabur MM (2007) Recognizing and treating nonmotor aspects of Parkinson’s disease. Ann Long Term Care 15(8)Google Scholar
  18. Camins A, Verdaguer E, Folch J, Canudas AM, Pallas M (2006) The role of CDK5/P25 formation/inhibition in neurodegeneration. Drug News Perspect 19(8):453–460. doi: 10.1358/dnp.2006.19.8.1043961 PubMedCrossRefGoogle Scholar
  19. Cao X, Sudhof TC (2001) A transcriptionally [correction of transcriptively] active complex of APP with Fe65 and histone acetyltransferase Tip60. Science 293(5527):115–120. doi: 10.1126/science.1058783293/5527/115 PubMedCrossRefGoogle Scholar
  20. Chen RZ, Akbarian S, Tudor M, Jaenisch R (2001) Deficiency of methyl-CpG binding protein-2 in CNS neurons results in a Rett-like phenotype in mice. Nat Genet 27(3):327–331. doi: 10.1038/85906 PubMedCrossRefGoogle Scholar
  21. Chen Y, Sharma RP, Costa RH, Costa E, Grayson DR (2002) On the epigenetic regulation of the human reelin promoter. Nucleic Acids Res 30(13):2930–2939PubMedCrossRefGoogle Scholar
  22. Chen KL, Wang SS, Yang YY, Yuan RY, Chen RM, Hu CJ (2009) The epigenetic effects of amyloid-beta(1–40) on global DNA and neprilysin genes in murine cerebral endothelial cells. Biochem Biophys Res Commun 378(1):57–61. doi: 10.1016/j.bbrc.2008.10.173 PubMedCrossRefGoogle Scholar
  23. Cheung WL, Turner FB, Krishnamoorthy T, Wolner B, Ahn SH, Foley M, Dorsey JA, Peterson CL, Berger SL, Allis CD (2005) Phosphorylation of histone H4 serine 1 during DNA damage requires casein kinase II in S. cerevisiae. Curr Biol 15(7):656–660. doi: 10.1016/j.cub.2005.02.049 PubMedCrossRefGoogle Scholar
  24. Chia N, Wang L, Lu X, Senut MC, Brenner C, Ruden DM (2011) Hypothesis: environmental regulation of 5-hydroxymethylcytosine by oxidative stress. Epigenetics 6(7):853–856PubMedCrossRefGoogle Scholar
  25. Chiurazzi P, Pomponi MG, Willemsen R, Oostra BA, Neri G (1998) In vitro reactivation of the FMR1 gene involved in fragile X syndrome. Hum Mol Genet 7(1):109–113PubMedCrossRefGoogle Scholar
  26. Chiurazzi P, Pomponi MG, Pietrobono R, Bakker CE, Neri G, Oostra BA (1999) Synergistic effect of histone hyperacetylation and DNA demethylation in the reactivation of the FMR1 gene. Hum Mol Genet 8(12):2317–2323PubMedCrossRefGoogle Scholar
  27. Cloos PA, Christensen J, Agger K, Helin K (2008) Erasing the methyl mark: histone demethylases at the center of cellular differentiation and disease. Genes Dev 22(9):1115–1140. doi: 10.1101/gad.1652908 PubMedCrossRefGoogle Scholar
  28. Conway KA, Lee SJ, Rochet JC, Ding TT, Williamson RE, Lansbury PT Jr (2000) Acceleration of oligomerization, not fibrillization, is a shared property of both alpha-synuclein mutations linked to early-onset Parkinson’s disease: implications for pathogenesis and therapy. Proc Natl Acad Sci USA 97(2):571–576PubMedCrossRefGoogle Scholar
  29. Costa E, Chen Y, Davis J, Dong E, Noh JS, Tremolizzo L, Veldic M, Grayson DR, Guidotti A (2002) REELIN and schizophrenia: a disease at the interface of the genome and the epigenome. Mol Interv 2(1):47–57. doi: 10.1124/mi.2.1.47 PubMedCrossRefGoogle Scholar
  30. Dai Y, Faller DV (2008) Transcription regulation by class III histone deacetylases (HDACs)—sirtuins. Transl Oncogenomics 3:53–65PubMedGoogle Scholar
  31. Ferrante RJ, Ryu H, Kubilus JK, D’Mello S, Sugars KL, Lee J, Lu P, Smith K, Browne S, Beal MF, Kristal BS, Stavrovskaya IG, Hewett S, Rubinsztein DC, Langley B, Ratan RR (2004) Chemotherapy for the brain: the antitumor antibiotic mithramycin prolongs survival in a mouse model of Huntington’s disease. J Neurosci 24(46):10335–10342. doi: 10.1523/JNEUROSCI.2599-04.2004 PubMedCrossRefGoogle Scholar
  32. Fischer A, Sananbenesi F, Wang X, Dobbin M, Tsai LH (2007) Recovery of learning and memory is associated with chromatin remodelling. Nature 447(7141):178–182. doi: 10.1038/nature05772 PubMedCrossRefGoogle Scholar
  33. Fishman-Jacob T, Reznichenko L, Youdim MB, Mandel SA (2009) A sporadic Parkinson disease model via silencing of the ubiquitin-proteasome/E3 ligase component SKP1A. J Biol Chem 284(47):32835–32845. doi: 10.1074/jbc.M109.034223 PubMedCrossRefGoogle Scholar
  34. Forneris F, Binda C, Vanoni MA, Battaglioli E, Mattevi A (2005) Human histone demethylase LSD1 reads the histone code. J Biol Chem 280(50):41360–41365. doi: 10.1074/jbc.M509549200 PubMedCrossRefGoogle Scholar
  35. Franco R, Li S, Rodriguez-Rocha H, Burns M, Panayiotidis MI (2010) Molecular mechanisms of pesticide-induced neurotoxicity: relevance to Parkinson’s disease. Chem Biol Interact 188(2):289–300. doi: 10.1016/j.cbi.2010.06.003 PubMedCrossRefGoogle Scholar
  36. Gao Z, Ye J (2008) Inhibition of transcriptional activity of c-JUN by SIRT1. Biochem Biophys Res Commun 376(4):793–796. doi: 10.1016/j.bbrc.2008.09.079 PubMedCrossRefGoogle Scholar
  37. Gardian G, Yang L, Cleren C, Calingasan NY, Klivenyi P, Beal MF (2004) Neuroprotective effects of phenylbutyrate against MPTP neurotoxicity. Neuromolecular Med 5(3):235–241. doi: 10.1385/NMM:5:3:235 PubMedCrossRefGoogle Scholar
  38. Gardian G, Browne SE, Choi DK, Klivenyi P, Gregorio J, Kubilus JK, Ryu H, Langley B, Ratan RR, Ferrante RJ, Beal MF (2005) Neuroprotective effects of phenylbutyrate in the N171-82Q transgenic mouse model of Huntington’s disease. J Biol Chem 280(1):556–563. doi: 10.1074/jbc.M410210200 PubMedGoogle Scholar
  39. Gasser T (2009a) Genomic and proteomic biomarkers for Parkinson disease. Neurology 72(7 Suppl):S27–S31. doi: 10.1212/WNL.0b013e318198e054 PubMedCrossRefGoogle Scholar
  40. Gasser T (2009b) Molecular pathogenesis of Parkinson disease: insights from genetic studies. Expert Rev Mol Med 11:e22. doi: 10.1017/S1462399409001148 PubMedCrossRefGoogle Scholar
  41. Gearhart MD, Corcoran CM, Wamstad JA, Bardwell VJ (2006) Polycomb group and SCF ubiquitin ligases are found in a novel BCOR complex that is recruited to BCL6 targets. Mol Cell Biol 26(18):6880–6889. doi: 10.1128/MCB.00630-06 PubMedCrossRefGoogle Scholar
  42. Geiss-Friedlander R, Melchior F (2007) Concepts in sumoylation: a decade on. Nat Rev Mol Cell Biol 8(12):947–956. doi: 10.1038/nrm2293 PubMedCrossRefGoogle Scholar
  43. Gooden DM, Schmidt DM, Pollock JA, Kabadi AM, McCafferty DG (2008) Facile synthesis of substituted trans-2-arylcyclopropylamine inhibitors of the human histone demethylase LSD1 and monoamine oxidases A and B. Bioorg Med Chem Lett 18(10):3047–3051. doi: 10.1016/j.bmcl.2008.01.003 PubMedCrossRefGoogle Scholar
  44. Grant PA (2001) A tale of histone modifications. Genome Biol 2(4):REVIEWS0003PubMedCrossRefGoogle Scholar
  45. Gregoire S, Tremblay AM, Xiao L, Yang Q, Ma K, Nie J, Mao Z, Wu Z, Giguere V, Yang XJ (2006) Control of MEF2 transcriptional activity by coordinated phosphorylation and sumoylation. J Biol Chem 281(7):4423–4433. doi: 10.1074/jbc.M509471200 PubMedCrossRefGoogle Scholar
  46. Guan JS, Haggarty SJ, Giacometti E, Dannenberg JH, Joseph N, Gao J, Nieland TJ, Zhou Y, Wang X, Mazitschek R, Bradner JE, DePinho RA, Jaenisch R, Tsai LH (2009) HDAC2 negatively regulates memory formation and synaptic plasticity. Nature 459(7243):55–60. doi: 10.1038/nature07925 PubMedCrossRefGoogle Scholar
  47. Guy J, Hendrich B, Holmes M, Martin JE, Bird A (2001) A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome. Nat Genet 27(3):322–326. doi: 10.1038/85899 PubMedCrossRefGoogle Scholar
  48. Haberland M, Montgomery RL, Olson EN (2009) The many roles of histone deacetylases in development and physiology: implications for disease and therapy. Nat Rev Genet 10(1):32–42. doi: 10.1038/nrg2485 PubMedCrossRefGoogle Scholar
  49. Hague SM, Klaffke S, Bandmann O (2005) Neurodegenerative disorders: Parkinson’s disease and Huntington's disease. J Neurol Neurosurg Psychiatry 76(8):1058–1063. doi: 10.1136/jnnp.2004.060186 PubMedCrossRefGoogle Scholar
  50. Hakimi MA, Bochar DA, Chenoweth J, Lane WS, Mandel G, Shiekhattar R (2002) A core-BRAF35 complex containing histone deacetylase mediates repression of neuronal-specific genes. Proc Natl Acad Sci USA 99(11):7420–7425. doi: 10.1073/pnas.112008599 PubMedCrossRefGoogle Scholar
  51. Hockly E, Richon VM, Woodman B, Smith DL, Zhou X, Rosa E, Sathasivam K, Ghazi-Noori S, Mahal A, Lowden PA, Steffan JS, Marsh JL, Thompson LM, Lewis CM, Marks PA, Bates GP (2003) Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, ameliorates motor deficits in a mouse model of Huntington’s disease. Proc Natl Acad Sci USA 100(4):2041–2046. doi: 10.1073/pnas.0437870100 PubMedCrossRefGoogle Scholar
  52. Huang HS, Akbarian S (2007) GAD1 mRNA expression and DNA methylation in prefrontal cortex of subjects with schizophrenia. PLoS One 2(8):e809. doi: 10.1371/journal.pone.0000809 PubMedCrossRefGoogle Scholar
  53. Huang HS, Matevossian A, Whittle C, Kim SY, Schumacher A, Baker SP, Akbarian S (2007a) Prefrontal dysfunction in schizophrenia involves mixed-lineage leukemia 1-regulated histone methylation at GABAergic gene promoters. J Neurosci 27(42):11254–11262. doi: 10.1523/JNEUROSCI.3272-07.2007 PubMedCrossRefGoogle Scholar
  54. Huang J, Sengupta R, Espejo AB, Lee MG, Dorsey JA, Richter M, Opravil S, Shiekhattar R, Bedford MT, Jenuwein T, Berger SL (2007b) p53 is regulated by the lysine demethylase LSD1. Nature 449(7158):105–108. doi: 10.1038/nature06092 PubMedCrossRefGoogle Scholar
  55. Hubble JP, Cao T, Hassanein RE, Neuberger JS, Koller WC (1993) Risk factors for Parkinson’s disease. Neurology 43(9):1693–1697PubMedGoogle Scholar
  56. Inzelberg R, Jankovic J (2007) Are Parkinson disease patients protected from some but not all cancers? Neurology 69(15):1542–1550. doi: 10.1212/01.wnl.0000277638.63767.b8 PubMedCrossRefGoogle Scholar
  57. Ishii A, Nonaka T, Taniguchi S, Saito T, Araic T, Mann D, Iwatsubo T, Hisanaga S, Goedert M, Hasegawa M (2007) Casein kinase 2 is the major enzyme in brain that phosphorylates Ser129 of human alpha-synuclein: Implication for alpha-synucleinopathies. FEBS Lett 581(24):4711–4717PubMedCrossRefGoogle Scholar
  58. Iwata A, Miura S, Kanazawa I, Sawada M, Nukina N (2001) Alpha-synuclein forms a complex with transcription factor Elk-1. J Neurochem 77(1):239–252PubMedCrossRefGoogle Scholar
  59. Jacobs FM, van Erp S, van der Linden AJ, von Oerthel L, Burbach JP, Smidt MP (2009) Pitx3 potentiates Nurr1 in dopamine neuron terminal differentiation through release of SMRT-mediated repression. Development 136(4):531–540. doi: 10.1242/dev.029769 PubMedCrossRefGoogle Scholar
  60. Jankovic J (2008) Parkinson’s disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry 79(4):368–376. doi: 10.1136/jnnp.2007.131045 PubMedCrossRefGoogle Scholar
  61. Jankovic J, Chen S, Le WD (2005) The role of Nurr1 in the development of dopaminergic neurons and Parkinson’s disease. Prog Neurobiol 77(1–2):128–138. doi: 10.1016/j.pneurobio.2005.09.001 PubMedCrossRefGoogle Scholar
  62. Jellinger KA (2000) Cell death mechanisms in Parkinson’s disease. J Neural Transm 107(1):1–29PubMedCrossRefGoogle Scholar
  63. Jenner P (2003) Oxidative stress in Parkinson’s disease. Ann Neurol 53(Suppl 3):S26–S36. doi: 10.1002/ana.10483 PubMedCrossRefGoogle Scholar
  64. Jenuwein T, Allis CD (2001) Translating the histone code. Science 293(5532):1074–1080PubMedCrossRefGoogle Scholar
  65. Jie Z, Li T, Jia-Yun H, Qiu J, Ping-Yao Z, Houyan S (2009) Trans-2-phenylcyclopropylamine induces nerve cells apoptosis in zebrafish mediated by depression of LSD1 activity. Brain Res Bull 80(1–2):79–84. doi: 10.1016/j.brainresbull.2009.04.013 PubMedCrossRefGoogle Scholar
  66. Jiricny J, Menigatti M (2008) DNA cytosine demethylation: are we getting close? Cell 135(7):1167–1169. doi: 10.1016/j.cell.2008.12.008 PubMedCrossRefGoogle Scholar
  67. Johnson KA, Conn PJ, Niswender CM (2009) Glutamate receptors as therapeutic targets for Parkinson’s disease. CNS Neurol Disord Drug Targets 8(6):475–491PubMedGoogle Scholar
  68. Joo HY, Zhai L, Yang C, Nie S, Erdjument-Bromage H, Tempst P, Chang C, Wang H (2007) Regulation of cell cycle progression and gene expression by H2A deubiquitination. Nature 449(7165):1068–1072. doi: 10.1038/nature06256 PubMedCrossRefGoogle Scholar
  69. Joseph B, Wallen-Mackenzie A, Benoit G, Murata T, Joodmardi E, Okret S, Perlmann T (2003) p57(Kip2) cooperates with Nurr1 in developing dopamine cells. Proc Natl Acad Sci USA 100(26):15619–15624. doi: 10.1073/pnas.2635658100 PubMedCrossRefGoogle Scholar
  70. Jowaed A, Schmitt I, Kaut O, Wullner U (2010) Methylation regulates alpha-synuclein expression and is decreased in Parkinson’s disease patients’ brains. J Neurosci 30(18):6355–6359. doi: 10.1523/JNEUROSCI.6119-09.2010 PubMedCrossRefGoogle Scholar
  71. Khochbin S, Kao HY (2001) Histone deacetylase complexes: functional entities or molecular reservoirs. FEBS Lett 494(3):141–144PubMedCrossRefGoogle Scholar
  72. Kim D, Nguyen MD, Dobbin MM, Fischer A, Sananbenesi F, Rodgers JT, Delalle I, Baur JA, Sui G, Armour SM, Puigserver P, Sinclair DA, Tsai LH (2007) SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer’s disease and amyotrophic lateral sclerosis. EMBO J 26(13):3169–3179. doi: 10.1038/sj.emboj.7601758 PubMedCrossRefGoogle Scholar
  73. Klose RJ, Zhang Y (2007) Regulation of histone methylation by demethylimination and demethylation. Nat Rev Mol Cell Biol 8(4):307–318. doi: 10.1038/nrm2143 PubMedCrossRefGoogle Scholar
  74. Kohno R, Sawada H, Kawamoto Y, Uemura K, Shibasaki H, Shimohama S (2004) BDNF is induced by wild-type alpha-synuclein but not by the two mutants, A30P or A53T, in glioma cell line. Biochem Biophys Res Commun 318(1):113–118. doi: 10.1016/j.bbrc.2004.04.012 PubMedCrossRefGoogle Scholar
  75. Konradi C, Westin JE, Carta M, Eaton ME, Kuter K, Dekundy A, Lundblad M, Cenci MA (2004) Transcriptome analysis in a rat model of L-DOPA-induced dyskinesia. Neurobiol Dis 17(2):219–236. doi: 10.1016/j.nbd.2004.07.005 PubMedCrossRefGoogle Scholar
  76. Kontopoulos E, Parvin JD, Feany MB (2006) Alpha-synuclein acts in the nucleus to inhibit histone acetylation and promote neurotoxicity. Hum Mol Genet 15(20):3012–3023. doi: 10.1093/hmg/ddl243 PubMedCrossRefGoogle Scholar
  77. Korzus E, Rosenfeld MG, Mayford M (2004) CBP histone acetyltransferase activity is a critical component of memory consolidation. Neuron 42(6):961–972. doi: 10.1016/j.neuron.2004.06.002 PubMedCrossRefGoogle Scholar
  78. Kouzarides T (2007) Chromatin modifications and their function. Cell 128(4):693–705. doi: 10.1016/j.cell.2007.02.005 PubMedCrossRefGoogle Scholar
  79. Koyama-Nasu R, David G, Tanese N (2007) The F-box protein Fbl10 is a novel transcriptional repressor of c-Jun. Nat Cell Biol 9(9):1074–1080. doi: 10.1038/ncb1628 PubMedCrossRefGoogle Scholar
  80. Kriaucionis S, Heintz N (2009) The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain. Science 324(5929):929–930. doi: 10.1126/science.1169786 PubMedCrossRefGoogle Scholar
  81. Latham JA, Dent SY (2007) Cross-regulation of histone modifications. Nat Struct Mol Biol 14(11):1017–1024. doi: 10.1038/nsmb1307 PubMedCrossRefGoogle Scholar
  82. Le W, Pan T, Huang M, Xu P, Xie W, Zhu W, Zhang X, Deng H, Jankovic J (2008) Decreased NURR1 gene expression in patients with Parkinson’s disease. J Neurol Sci 273(1–2):29–33. doi: 10.1016/j.jns.2008.06.007 PubMedCrossRefGoogle Scholar
  83. Leng Y, Chuang DM (2006) Endogenous alpha-synuclein is induced by valproic acid through histone deacetylase inhibition and participates in neuroprotection against glutamate-induced excitotoxicity. J Neurosci 26(28):7502–7512. doi: 10.1523/JNEUROSCI.0096-06.2006 PubMedCrossRefGoogle Scholar
  84. Lesage S, Brice A (2009) Parkinson’s disease: from monogenic forms to genetic susceptibility factors. Hum Mol Genet 18(R1):R48–R59. doi: 10.1093/hmg/ddp012 PubMedCrossRefGoogle Scholar
  85. Levy OA, Malagelada C, Greene LA (2009) Cell death pathways in Parkinson’s disease: proximal triggers, distal effectors, and final steps. Apoptosis 14(4):478–500. doi: 10.1007/s10495-008-0309-3 PubMedCrossRefGoogle Scholar
  86. Li W, Liu M (2011) Distribution of 5-hydroxymethylcytosine in different human tissues. J Nucleic Acids 2011:870726. doi: 10.4061/2011/870726 PubMedGoogle Scholar
  87. Li YJ, Fu XH, Liu DP, Liang CC (2004) Opening the chromatin for transcription. Int J Biochem Cell Biol 36(8):1411–1423. doi: 10.1016/j.biocel.2003.11.003 PubMedCrossRefGoogle Scholar
  88. Li J, Dani JA, Le W (2009) The role of transcription factor Pitx3 in dopamine neuron development and Parkinson’s disease. Curr Top Med Chem 9(10):855–859PubMedGoogle Scholar
  89. Lim ACB, Hou ZB, Goh CP, Qi RZ (2004) Protein kinase CK2 is an inhibitor of the neuronal Cdk5 kinase. J Biol Chem 279(45):46668–46673PubMedCrossRefGoogle Scholar
  90. Liu M, Aneja R, Sun X, Xie S, Wang H, Wu X, Dong JT, Li M, Joshi HC, Zhou J (2008) Parkin regulates Eg5 expression by Hsp70 ubiquitination-dependent inactivation of c-Jun NH2-terminal kinase. J Biol Chem 283(51):35783–35788. doi: 10.1074/jbc.M806860200 PubMedCrossRefGoogle Scholar
  91. Luthi-Carter R, Taylor DM, Pallos J, Lambert E, Amore A, Parker A, Moffitt H, Smith DL, Runne H, Gokce O, Kuhn A, Xiang Z, Maxwell MM, Reeves SA, Bates GP, Neri C, Thompson LM, Marsh JL, Kazantsev AG (2010) SIRT2 inhibition achieves neuroprotection by decreasing sterol biosynthesis. Proc Natl Acad Sci USA 107(17):7927–7932. doi: 10.1073/pnas.1002924107 PubMedCrossRefGoogle Scholar
  92. MacDonald JL, Roskams AJ (2008) Histone deacetylases 1 and 2 are expressed at distinct stages of neuro-glial development. Dev Dyn 237(8):2256–2267. doi: 10.1002/dvdy.21626 PubMedCrossRefGoogle Scholar
  93. Mandel SA, Fishman T, Youdim MB (2007) Gene and protein signatures in sporadic Parkinson’s disease and a novel genetic model of PD. Parkinsonism Relat Disord 13(Suppl 3):S242–S247. doi: 10.1016/S1353-8020(08)70009-9 PubMedCrossRefGoogle Scholar
  94. Marambaud P, Wen PH, Dutt A, Shioi J, Takashima A, Siman R, Robakis NK (2003) A CBP binding transcriptional repressor produced by the PS1/epsilon-cleavage of N-cadherin is inhibited by PS1 FAD mutations. Cell 114(5):635–645PubMedCrossRefGoogle Scholar
  95. Martinowich K, Hattori D, Wu H, Fouse S, He F, Hu Y, Fan G, Sun YE (2003) DNA methylation-related chromatin remodeling in activity-dependent BDNF gene regulation. Science 302(5646):890–893. doi: 10.1126/science.1090842 PubMedCrossRefGoogle Scholar
  96. Matsumoto L, Takuma H, Tamaoka A, Kurisaki H, Date H, Tsuji S, Iwata A (2010) CpG demethylation enhances alpha-synuclein expression and affects the pathogenesis of Parkinson’s disease. PLoS One 5(11):e15522. doi: 10.1371/journal.pone.0015522 PubMedCrossRefGoogle Scholar
  97. Maze I, Covington HE 3rd, Dietz DM, LaPlant Q, Renthal W, Russo SJ, Mechanic M, Mouzon E, Neve RL, Haggarty SJ, Ren Y, Sampath SC, Hurd YL, Greengard P, Tarakhovsky A, Schaefer A, Nestler EJ (2010) Essential role of the histone methyltransferase G9a in cocaine-induced plasticity. Science 327(5962):213–216. doi: 10.1126/science.1179438 PubMedCrossRefGoogle Scholar
  98. Mena MA, Rodriguez-Navarro JA, Ros R, de Yebenes JG (2008) On the pathogenesis and neuroprotective treatment of Parkinson disease: what have we learned from the genetic forms of this disease? Curr Med Chem 15(23):2305–2320PubMedCrossRefGoogle Scholar
  99. Michishita E, Park JY, Burneskis JM, Barrett JC, Horikawa I (2005) Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins. Mol Biol Cell 16(10):4623–4635PubMedCrossRefGoogle Scholar
  100. Migliore L, Coppede F (2009) Genetics, environmental factors and the emerging role of epigenetics in neurodegenerative diseases. Mutat Res 667(1–2):82–97. doi: 10.1016/j.mrfmmm.2008.10.011 PubMedGoogle Scholar
  101. Mimasu S, Sengoku T, Fukuzawa S, Umehara T, Yokoyama S (2008) Crystal structure of histone demethylase LSD1 and tranylcypromine at 2.25 A. Biochem Biophys Res Commun 366(1):15–22. doi: 10.1016/j.bbrc.2007.11.066 PubMedCrossRefGoogle Scholar
  102. Miranda TB, Jones PA (2007) DNA methylation: the nuts and bolts of repression. J Cell Physiol 213(2):384–390. doi: 10.1002/jcp.21224 PubMedCrossRefGoogle Scholar
  103. Mogi M, Kondo T, Mizuno Y, Nagatsu T (2007) p53 protein, interferon-gamma, and NF-kappaB levels are elevated in the parkinsonian brain. Neurosci Lett 414(1):94–97. doi: 10.1016/j.neulet.2006.12.003 PubMedCrossRefGoogle Scholar
  104. Monaco L, Kolthur-Seetharam U, Loury R, Murcia JM, de Murcia G, Sassone-Corsi P (2005) Inhibition of Aurora-B kinase activity by poly(ADP-ribosyl)ation in response to DNA damage. Proc Natl Acad Sci USA 102(40):14244–14248. doi: 10.1073/pnas.0506252102 PubMedCrossRefGoogle Scholar
  105. Monier K, Mouradian S, Sullivan KF (2007) DNA methylation promotes Aurora-B-driven phosphorylation of histone H3 in chromosomal subdomains. J Cell Sci 120(Pt 1):101–114. doi: 10.1242/jcs.03326 PubMedGoogle Scholar
  106. Nair VD, McNaught KS, Gonzalez-Maeso J, Sealfon SC, Olanow CW (2006) p53 mediates nontranscriptional cell death in dopaminergic cells in response to proteasome inhibition. J Biol Chem 281(51):39550–39560. doi: 10.1074/jbc.M603950200 PubMedCrossRefGoogle Scholar
  107. Narlikar GJ, Fan HY, Kingston RE (2002) Cooperation between complexes that regulate chromatin structure and transcription. Cell 108(4):475–487PubMedCrossRefGoogle Scholar
  108. Nicholas AP, Lubin FD, Hallett PJ, Vattem P, Ravenscroft P, Bezard E, Zhou S, Fox SH, Brotchie JM, Sweatt JD, Standaert DG (2008) Striatal histone modifications in models of levodopa-induced dyskinesia. J Neurochem 106(1):486–494. doi: 10.1111/j.1471-4159.2008.05417.x PubMedCrossRefGoogle Scholar
  109. Nicholson TB, Chen T (2009) LSD1 demethylates histone and non-histone proteins. Epigenetics 4(3):129–132PubMedCrossRefGoogle Scholar
  110. Oei SL, Griesenbeck J, Schweiger M, Ziegler M (1998) Regulation of RNA polymerase II-dependent transcription by poly(ADP-ribosyl)ation of transcription factors. J Biol Chem 273(48):31644–31647PubMedCrossRefGoogle Scholar
  111. Outeiro TF, Grammatopoulos TN, Altmann S, Amore A, Standaert DG, Hyman BT, Kazantsev AG (2007a) Pharmacological inhibition of PARP-1 reduces alpha-synuclein- and MPP+-induced cytotoxicity in Parkinson’s disease in vitro models. Biochem Biophys Res Commun 357(3):596–602. doi: 10.1016/j.bbrc.2007.03.163 PubMedCrossRefGoogle Scholar
  112. Outeiro TF, Kontopoulos E, Altmann SM, Kufareva I, Strathearn KE, Amore AM, Volk CB, Maxwell MM, Rochet JC, McLean PJ, Young AB, Abagyan R, Feany MB, Hyman BT, Kazantsev AG (2007b) Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson’s disease. Science 317(5837):516–519. doi: 10.1126/science.1143780 PubMedCrossRefGoogle Scholar
  113. Pieper HC, Evert BO, Kaut O, Riederer PF, Waha A, Wullner U (2008) Different methylation of the TNF-alpha promoter in cortex and substantia nigra: Implications for selective neuronal vulnerability. Neurobiol Dis 32(3):521–527. doi: 10.1016/j.nbd.2008.09.010 PubMedCrossRefGoogle Scholar
  114. Renthal W, Nestler EJ (2008) Epigenetic mechanisms in drug addiction. Trends Mol Med 14(8):341–350. doi: 10.1016/j.molmed.2008.06.004 PubMedCrossRefGoogle Scholar
  115. Roelfsema JH, White SJ, Ariyurek Y, Bartholdi D, Niedrist D, Papadia F, Bacino CA, den Dunnen JT, van Ommen GJ, Breuning MH, Hennekam RC, Peters DJ (2005) Genetic heterogeneity in Rubinstein–Taybi syndrome: mutations in both the CBP and EP300 genes cause disease. Am J Hum Genet 76(4):572–580. doi: 10.1086/429130 PubMedCrossRefGoogle Scholar
  116. Roth SY, Denu JM, Allis CD (2001) Histone acetyltransferases. Annu Rev Biochem 70:81–120. doi: 10.1146/annurev.biochem.70.1.81 PubMedCrossRefGoogle Scholar
  117. Rouaux C, Jokic N, Mbebi C, Boutillier S, Loeffler JP, Boutillier AL (2003) Critical loss of CBP/p300 histone acetylase activity by caspase-6 during neurodegeneration. EMBO J 22(24):6537–6549. doi: 10.1093/emboj/cdg615 PubMedCrossRefGoogle Scholar
  118. Saijo K, Winner B, Carson CT, Collier JG, Boyer L, Rosenfeld MG, Gage FH, Glass CK (2009) A Nurr1/CoREST pathway in microglia and astrocytes protects dopaminergic neurons from inflammation-induced death. Cell 137(1):47–59. doi: 10.1016/j.cell.2009.01.038 PubMedCrossRefGoogle Scholar
  119. Santpere G, Nieto M, Puig B, Ferrer I (2006) Abnormal Sp1 transcription factor expression in Alzheimer disease and tauopathies. Neurosci Lett 397(1–2):30–34. doi: 10.1016/j.neulet.2005.11.062 PubMedCrossRefGoogle Scholar
  120. Saura CA, Choi SY, Beglopoulos V, Malkani S, Zhang D, Shankaranarayana Rao BS, Chattarji S, Kelleher RJ 3rd, Kandel ER, Duff K, Kirkwood A, Shen J (2004) Loss of presenilin function causes impairments of memory and synaptic plasticity followed by age-dependent neurodegeneration. Neuron 42(1):23–36PubMedCrossRefGoogle Scholar
  121. Scarpa S, Fuso A, D’Anselmi F, Cavallaro RA (2003) Presenilin 1 gene silencing by S-adenosylmethionine: a treatment for Alzheimer disease? FEBS Lett 541(1–3):145–148PubMedCrossRefGoogle Scholar
  122. Scoumanne A, Chen X (2007) The lysine-specific demethylase 1 is required for cell proliferation in both p53-dependent and -independent manners. J Biol Chem 282(21):15471–15475. doi: 10.1074/jbc.M701023200 PubMedCrossRefGoogle Scholar
  123. Scoumanne A, Chen X (2008) Protein methylation: a new mechanism of p53 tumor suppressor regulation. Histol Histopathol 23(9):1143–1149PubMedGoogle Scholar
  124. Shahbazian M, Young J, Yuva-Paylor L, Spencer C, Antalffy B, Noebels J, Armstrong D, Paylor R, Zoghbi H (2002) Mice with truncated MeCP2 recapitulate many Rett syndrome features and display hyperacetylation of histone H3. Neuron 35(2):243–254PubMedCrossRefGoogle Scholar
  125. Shi Y, Whetstine JR (2007) Dynamic regulation of histone lysine methylation by demethylases. Mol Cell 25(1):1–14. doi: 10.1016/j.molcel.2006.12.010 PubMedCrossRefGoogle Scholar
  126. Shi Y, Lan F, Matson C, Mulligan P, Whetstine JR, Cole PA, Casero RA (2004) Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell 119(7):941–953. doi: 10.1016/j.cell.2004.12.012 PubMedCrossRefGoogle Scholar
  127. Shi YJ, Matson C, Lan F, Iwase S, Baba T, Shi Y (2005) Regulation of LSD1 histone demethylase activity by its associated factors. Mol Cell 19(6):857–864. doi: 10.1016/j.molcel.2005.08.027 PubMedCrossRefGoogle Scholar
  128. Siegmund KD, Connor CM, Campan M, Long TI, Weisenberger DJ, Biniszkiewicz D, Jaenisch R, Laird PW, Akbarian S (2007) DNA methylation in the human cerebral cortex is dynamically regulated throughout the life span and involves differentiated neurons. PLoS One 2(9):e895. doi: 10.1371/journal.pone.0000895 PubMedCrossRefGoogle Scholar
  129. Smith PD, Mount MP, Shree R, Callaghan S, Slack RS, Anisman H, Vincent I, Wang X, Mao Z, Park DS (2006) Calpain-regulated p35/cdk5 plays a central role in dopaminergic neuron death through modulation of the transcription factor myocyte enhancer factor 2. J Neurosci 26(2):440–447. doi: 10.1523/JNEUROSCI.2875-05.2006 PubMedCrossRefGoogle Scholar
  130. Spencer VA, Davie JR (1999) Role of covalent modifications of histones in regulating gene expression. Gene 240(1):1–12PubMedCrossRefGoogle Scholar
  131. Stack EC, Del Signore SJ, Luthi-Carter R, Soh BY, Goldstein DR, Matson S, Goodrich S, Markey AL, Cormier K, Hagerty SW, Smith K, Ryu H, Ferrante RJ (2007) Modulation of nucleosome dynamics in Huntington’s disease. Hum Mol Genet 16(10):1164–1175. doi: 10.1093/hmg/ddm064 PubMedCrossRefGoogle Scholar
  132. Steffan JS, Bodai L, Pallos J, Poelman M, McCampbell A, Apostol BL, Kazantsev A, Schmidt E, Zhu YZ, Greenwald M, Kurokawa R, Housman DE, Jackson GR, Marsh JL, Thompson LM (2001) Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila. Nature 413(6857):739–743. doi: 10.1038/35099568 PubMedCrossRefGoogle Scholar
  133. Sterner DE, Berger SL (2000) Acetylation of histones and transcription-related factors. Microbiol Mol Biol Rev 64(2):435–459PubMedCrossRefGoogle Scholar
  134. Strahl BD, Allis CD (2000) The language of covalent histone modifications. Nature 403(6765):41–45PubMedCrossRefGoogle Scholar
  135. Sugars KL, Brown R, Cook LJ, Swartz J, Rubinsztein DC (2004) Decreased cAMP response element-mediated transcription: an early event in exon 1 and full-length cell models of Huntington’s disease that contributes to polyglutamine pathogenesis. J Biol Chem 279(6):4988–4999. doi: 10.1074/jbc.M310226200 PubMedCrossRefGoogle Scholar
  136. Szargel R, Rott R, Engelender S (2008) Synphilin-1 isoforms in Parkinson’s disease: regulation by phosphorylation and ubiquitylation. Cell Mol Life Sci 65(1):80–88. doi: 10.1007/s00018-007-7343-0 PubMedCrossRefGoogle Scholar
  137. Tabolacci E, Pietrobono R, Moscato U, Oostra BA, Chiurazzi P, Neri G (2005) Differential epigenetic modifications in the FMR1 gene of the fragile X syndrome after reactivating pharmacological treatments. Eur J Hum Genet 13(5):641–648. doi: 10.1038/sj.ejhg.5201393 PubMedCrossRefGoogle Scholar
  138. Tabolacci E, Moscato U, Zalfa F, Bagni C, Chiurazzi P, Neri G (2008) Epigenetic analysis reveals a euchromatic configuration in the FMR1 unmethylated full mutations. Eur J Hum Genet 16(12):1487–1498. doi: 10.1038/ejhg.2008.130 PubMedCrossRefGoogle Scholar
  139. Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H, Brudno Y, Agarwal S, Iyer LM, Liu DR, Aravind L, Rao A (2009) Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324(5929):930–935. doi: 10.1126/science.1170116 PubMedCrossRefGoogle Scholar
  140. Takai D, Jones PA (2002) Comprehensive analysis of CpG islands in human chromosomes 21 and 22. Proc Natl Acad Sci USA 99(6):3740–3745. doi: 10.1073/pnas.052410099 PubMedCrossRefGoogle Scholar
  141. Tang BL, Chua CE (2008) SIRT1 and neuronal diseases. Mol Aspects Med 29(3):187–200. doi: 10.1016/j.mam.2007.02.001 PubMedCrossRefGoogle Scholar
  142. Tang X, Wang X, Gong X, Tong M, Park D, Xia Z, Mao Z (2005) Cyclin-dependent kinase 5 mediates neurotoxin-induced degradation of the transcription factor myocyte enhancer factor 2. J Neurosci 25(19):4823–4834. doi: 10.1523/JNEUROSCI.1331-05.2005 PubMedCrossRefGoogle Scholar
  143. Tanner CM, Ottman R, Goldman SM, Ellenberg J, Chan P, Mayeux R, Langston JW (1999) Parkinson disease in twins: an etiologic study. JAMA 281(4):341–346PubMedCrossRefGoogle Scholar
  144. Taverna SD, Li H, Ruthenburg AJ, Allis CD, Patel DJ (2007) How chromatin-binding modules interpret histone modifications: lessons from professional pocket pickers. Nat Struct Mol Biol 14(11):1025–1040PubMedCrossRefGoogle Scholar
  145. Thalhammer A, Hansen AS, El-Sagheer AH, Brown T, Schofield CJ (2011) Hydroxylation of methylated CpG dinucleotides reverses stabilisation of DNA duplexes by cytosine 5-methylation. Chem Commun (Camb) 47(18):5325–5327. doi: 10.1039/c0cc05671e CrossRefGoogle Scholar
  146. Topark-Ngarm A, Golonzhka O, Peterson VJ, Barrett B Jr, Martinez B, Crofoot K, Filtz TM, Leid M (2006) CTIP2 associates with the NuRD complex on the promoter of p57KIP2, a newly identified CTIP2 target gene. J Biol Chem 281(43):32272–32283. doi: 10.1074/jbc.M602776200 PubMedCrossRefGoogle Scholar
  147. Tsai WW, Nguyen TT, Shi Y, Barton MC (2008) p53-targeted LSD1 functions in repression of chromatin structure and transcription in vivo. Mol Cell Biol 28(17):5139–5146. doi: 10.1128/MCB.00287-08 PubMedCrossRefGoogle Scholar
  148. Turner BM (2002) Cellular memory and the histone code. Cell 111(3):285–291PubMedCrossRefGoogle Scholar
  149. Verdin E, Dequiedt F, Kasler HG (2003) Class II histone deacetylases: versatile regulators. Trends Genet 19(5):286–293PubMedCrossRefGoogle Scholar
  150. Wang SC, Oelze B, Schumacher A (2008) Age-specific epigenetic drift in late-onset Alzheimer’s disease. PLoS One 3(7):e2698. doi: 10.1371/journal.pone.0002698 PubMedCrossRefGoogle Scholar
  151. Wang Y, Zhang H, Chen Y, Sun Y, Yang F, Yu W, Liang J, Sun L, Yang X, Shi L, Li R, Li Y, Zhang Y, Li Q, Yi X, Shang Y (2009) LSD1 is a subunit of the NuRD complex and targets the metastasis programs in breast cancer. Cell 138(4):660–672. doi: 10.1016/j.cell.2009.05.050 PubMedCrossRefGoogle Scholar
  152. Wu J, Basha MR, Brock B, Cox DP, Cardozo-Pelaez F, McPherson CA, Harry J, Rice DC, Maloney B, Chen D, Lahiri DK, Zawia NH (2008) Alzheimer’s disease (AD)-like pathology in aged monkeys after infantile exposure to environmental metal lead (Pb): evidence for a developmental origin and environmental link for AD. J Neurosci 28(1):3–9. doi: 10.1523/JNEUROSCI.4405-07.2008 PubMedCrossRefGoogle Scholar
  153. Yang JO, Kim WY, Jeong SY, Oh JH, Jho S, Bhak J, Kim NS (2009a) PDbase: a database of Parkinson’s disease-related genes and genetic variation using substantia nigra ESTs. BMC Genomics 10(Suppl 3):S32. doi: 10.1186/1471-2164-10-S3-S32 PubMedCrossRefGoogle Scholar
  154. Yang Q, She H, Gearing M, Colla E, Lee M, Shacka JJ, Mao Z (2009b) Regulation of neuronal survival factor MEF2D by chaperone-mediated autophagy. Science 323(5910):124–127. doi: 10.1126/science.1166088 PubMedCrossRefGoogle Scholar
  155. Yeung F, Hoberg JE, Ramsey CS, Keller MD, Jones DR, Frye RA, Mayo MW (2004) Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J 23(12):2369–2380. doi: 10.1038/sj.emboj.7600244 PubMedCrossRefGoogle Scholar
  156. Zhao X, Sternsdorf T, Bolger TA, Evans RM, Yao TP (2005) Regulation of MEF2 by histone deacetylase 4- and SIRT1 deacetylase-mediated lysine modifications. Mol Cell Biol 25(19):8456–8464. doi: 10.1128/MCB.25.19.8456-8464.2005 PubMedCrossRefGoogle Scholar
  157. Zhou W, Wang X, Rosenfeld MG (2009) Histone H2A ubiquitination in transcriptional regulation and DNA damage repair. Int J Biochem Cell Biol 41(1):12–15. doi: 10.1016/j.biocel.2008.09.016 PubMedCrossRefGoogle Scholar
  158. Zuccato C, Cattaneo E (2009) Brain-derived neurotrophic factor in neurodegenerative diseases. Nat Rev Neurol 5(6):311–322. doi: 10.1038/nrneurol.2009.54 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  1. 1.Laboratory of Systems Biology and Bioinformatics (LBB), Institute of Biochemistry and Biophysics and Center of Excellence in BiomathematicsUniversity of TehranTehranIran
  2. 2.Genetics ProgramBoston University School of MedicineBostonUSA
  3. 3.Center for Human Genetic Research, Massachusetts General HospitalHarvard Medical SchoolBostonUSA

Personalised recommendations