Impaired DNA damage repair as a common feature of neurodegenerative diseases and psychiatric disorders

Current Molecular Medicine

Volumn 15, Issue 2, 2015, Pages 119-128

  Shiwaku, H ^a   Okazawa, H ^a,b  

^a TOKYO MEDICAL AND DENTAL UNIVERSITY   (Japan)

^b JAPAN SCIENCE AND TECHNOLOGY AGENCY   (Japan)

Author keywords

Alzheimer s disease; DNA damage; Huntington s disease; Microcephaly; Schizophrenia

Indexed keywords

REACTIVE OXYGEN METABOLITE; SIRTUIN 1; DNA; NEUROLEPTIC AGENT;

ALZHEIMER DISEASE; APOPTOSIS; ARTICLE; COGNITIVE DEFECT; DEGENERATIVE DISEASE; DNA DAMAGE; DNA METHYLATION; DNA REPAIR; DOUBLE STRANDED DNA BREAK REPAIR; DOWN REGULATION; ENDOPHENOTYPE; EXCISION REPAIR; GENE EXPRESSION; IMMUNOHISTOCHEMISTRY; MENTAL DISEASE; MICROCEPHALY; NONHUMAN; OXIDATIVE STRESS; PHENOTYPE; PROTEIN EXPRESSION; SCHIZOPHRENIA; SINGLE STRANDED DNA BREAK; BRAIN; DOUBLE STRANDED DNA BREAK; DRUG EFFECTS; GENETICS; HUMAN; HUNTINGTON CHOREA; INTELLECTUAL IMPAIRMENT; METABOLISM; NERVE CELL; PATHOLOGY; PATHOPHYSIOLOGY; SYNAPSE; SYNAPTIC TRANSMISSION;

ANTIPSYCHOTIC AGENTS; BRAIN; DNA; DNA BREAKS, DOUBLE-STRANDED; DNA REPAIR; HUMANS; HUNTINGTON DISEASE; INTELLECTUAL DISABILITY; MICROCEPHALY; NEURONS; PHENOTYPE; SCHIZOPHRENIA; SYNAPSES; SYNAPTIC TRANSMISSION;

EID: 84930974976     PISSN: 15665240     EISSN: 18755666     Source Type: Journal    
DOI: 10.2174/1566524015666150303002556     Document Type: Article

References (145)

1. Ross CA, Poirier MA. Protein aggregation and neurodegenerative disease. Nat Med 2004; 10 Suppl: S10-7.
2. Geser F, Martinez-Lage M, Kwong LK, et al. Amyotrophic lateral sclerosis, frontotemporal dementia and beyond: the TDP-43 diseases. J Neurol 2009; 256: 1205-14.
3. Mackenzie IR, Rademakers R, Neumann M. TDP-43 and FUS in amyotrophic lateral sclerosis and frontotemporal dementia. Lancet Neurol 2010; 9: 995-1007.
4. Doi H, Okamura K, Bauer PO, et al. RNA-binding protein TLS is a major nuclear aggregate-interacting protein in huntingtin exon 1 with expanded polyglutamine-expressing cells. J Biol Chem 2008; 283: 6489-500.
5. Woulfe J, Gray DA, Mackenzie IR. FUS-immunoreactive intranuclear inclusions in neurodegenerative disease. Brain Pathol 2010; 20: 589-97.
6. Imafuku I, Waragai M, Takeuchi S, et al. Polar amino acidrich sequences bind to polyglutamine tracts. Biochem Biophys Res Commun 1998; 253: 16-20.
7. Okazawa H, Rich T, Chang A, et al. Interaction between mutant ataxin-1 and PQBP-1 affects transcription and cell death. Neuron 2002; 34: 701-13.
8. Kalscheuer VM, Freude K, Musante L, et al. Mutations in the polyglutamine binding protein 1 gene cause X-linked mental retardation. Nat Genet 2003; 35: 313-5.
9. Ito H, Yoshimura N, Kurosawa M, et al. Knock-down of PQBP1 impairs anxiety-related cognition in mouse. Hum Mol Genet 2009; 18: 4239-54.
10. Tamura T, Horiuchi D, Chen YC, et al. Drosophila PQBP1 regulates learning acquisition at projection neurons in aversive olfactory conditioning. J Neurosci 2010; 30: 14091-101.
11. McCampbell A, Taylor JP, Taye AA, et al. CREB-binding protein sequestration by expanded polyglutamine. Hum Mol Genet 2000; 9: 2197-202.
12. Steffan JS, Bodai L, Pallos J, et al. Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila. Nature 2001; 413: 739-43.
13. Giralt A, Puigdellivol M, Carreton O, et al. Long-term memory deficits in Huntington's disease are associated with reduced CBP histone acetylase activity. Hum Mol Genet 2012; 21: 1203-16.
14. Ehrnhoefer DE, Wong BK, Hayden MR. Convergent pathogenic pathways in Alzheimer's and Huntington's diseases: shared targets for drug development. Nat Rev Drug Discov 2011; 10: 853-67.
15. Nagai M, Re DB, Nagata T, et al. Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons. Nat Neurosci 2007; 10: 615-22.
16. Shin JY, Fang ZH, Yu ZX, et al. Expression of mutant huntingtin in glial cells contributes to neuronal excitotoxicity. J Cell Biol 2005; 171(6): 1001-12.
17. Shiwaku H, Yoshimura N, Tamura T, et al. Suppression of the novel ER protein Maxer by mutant ataxin-1 in Bergman glia contributes to non-cell-autonomous toxicity. EMBO J 2010; 29: 2446-60.
18. Custer SK, Garden GA, Gill N, et al. Bergmann glia expression of polyglutamine-expanded ataxin-7 produces neurodegeneration by impairing glutamate transport. Nat Neurosci 2006; 9: 1302-11.
19. Penzes P, Buonanno A, Passafaro M, et al. Developmental vulnerability of synapses and circuits associated with neuropsychiatric disorders. J Neurochem 2013; 126: 165-82.
20. Chattopadhyaya B, Cristo GD. GABAergic circuit dysfunctions in neurodevelopmental disorders. Front Psychiatry 2012; 3: 51.
21. Kazantsev AG, Hersch SM. Drug targeting of dysregulated transcription in Huntington's disease. Prog Neurobiol 2007; 83: 249-59.
22. Fujita K, Nakamura Y, Oka T, et al. A functional deficiency of TERA/VCP/p97 contributes to impaired DNA repair in multiple polyglutamine diseases. Nat Commun 2013; 4: 1816.
23. Rulten SL, Caldecott KW. DNA strand break repair and neurodegeneration. DNA Repair (Amst) 2013; 12: 558-67.
24. Iyama T, Wilson DM III. DNA repair mechanisms in dividing and non-dividing cells. DNA Repair (Amst) 2013; 12: 620-36.
25. Stracker TH, Petrini JH. The MRE11 complex: starting from the ends. Nat Rev Mol Cell Biol 2011; 12: 90-103.
26. Chrzanowska KH, Gregorek H, Dembowska-Bagińska B, et al. Nijmegen breakage syndrome (NBS). Orphanet J Rare Dis 2012; 7: 13.
27. Waltes R, Kalb R, Gatei M, et al. Human RAD50 deficiency in a Nijmegen breakage syndrome-like disorder. Am J Hum Genet 2009; 84: 605-16.
28. Shull ER, Lee Y, Nakane H, et al. Differential DNA damage signaling accounts for distinct neural apoptotic responses in ATLD and NBS. Genes Dev 2009; 23: 171-80.
29. Sugawara M, Wada C, Okawa S, et al. Purkinje cell loss in the cerebellar flocculus in patients with ataxia with ocular motor apraxia type 1/early-onset ataxia with ocular motor apraxia and hypoalbuminemia. Eur Neurol 2008; 59: 18-23
30. Takashima H, Boerkoel CF, John J, et al. Mutation of TDP1, encoding a topoisomerase I-dependent DNA damage repair enzyme, in spinocerebellar ataxia with axonal neuropathy. Nat Genet 2002; 32: 267-72.
31. Reynolds JJ, Stewart GS. A single strand that links multiple neuropathologies in human disease. Brain 2013; 136: 14-27.
32. Mahmood S, Ahmad W, Hassan MJ. Autosomal Recessive Primary Microcephaly (MCPH): clinical manifestations, genetic heterogeneity and mutation continuum. Orphanet J Rare Dis 2011; 6: 39.
33. Singh N, Basnet H, Wiltshire TD, et al. Dual recognition of phosphoserine and phosphotyrosine in histone variant H2A.X by DNA damage response protein MCPH1. Proc Natl Acad Sci USA 2012; 109: 14381-6.
34. Lin SY, Rai R, Li K, Xu ZX, Elledge SJ. BRIT1/MCPH1 is a DNA damage responsive protein that regulates the Brca1-Chk1 pathway, implicating checkpoint dysfunction in microcephaly. Proc Natl Acad Sci USA 2005; 102: 15105-9.
35. Gruber R, Zhou Z, Sukchev M, et al. MCPH1 regulates the neuroprogenitor division mode by coupling the centrosomal cycle with mitotic entry through the Chk1-Cdc25 pathway. Nat Cell Biol 2011; 13: 1325-34.
36. McIntyre RE, Lakshminarasimhan Chavali P, Ismail O, et al. Disruption of mouse Cenpj, a regulator of centriole biogenesis, phenocopies Seckel syndrome. PLoS Genet 2012; 8: e1003022.
37. Lizarraga SB, Margossian SP, Harris MH, et al. Cdk5rap2 regulates centrosome function and chromosome segregation in neuronal progenitors. Development 2010; 137: 1907-17.
38. Sartori AA, Lukas C, Coates J, et al. Human CtIP promotes DNA end resection. Nature 2007; 450: 509-14.
39. McIlwraith MJ, Van Dyck E, Masson JY, et al. Reconstitution of the strand invasion step of double-strand break repair using human Rad51 Rad52 and RPA proteins. J Mol Biol 2000; 304: 151-64.
40. Jensen RB, Carreira A, Kowalczykowski SC. Purified human BRCA2 stimulates RAD51-mediated recombination. Nature 2010; 467: 678-83.
41. Ma Y, Pannicke U, Schwarz K, Lieber MR. Hairpin opening and overhang processing by an Artemis/DNA-dependent protein kinase complex in nonhomologous end joining and V(D)J recombination. Cell 2002; 108: 781-94.
42. Koch CA, Agyei R, Galicia S, et al. Xrcc4 physically links DNA end processing by polynucleotide kinase to DNA ligation by DNA ligase IV. EMBO J 2004; 23: 3874-85.
43. Ahnesorg P, Smith P, Jackson SP. XLF interacts with the XRCC4-DNA ligase IV complex to promote DNA nonhomologous end-joining. Cell 2006; 124: 301-13.
44. Orii KE, Lee Y, Kondo N, McKinnon PJ. Selective utilization of nonhomologous end-joining and homologous recombination DNA repair pathways during nervous system development. Proc Natl Acad Sci U S A. 2006; 103: 10017-22.
45. Gatz SA, Ju L, Gruber R, et al. Requirement for DNA ligase IV during embryonic neuronal development. J Neurosci 2011; 31: 10088-100.
46. Moshous D, Callebaut I, de Chasseval R, et al. Artemis, a novel DNA double-strand break repair/V(D)J recombination protein, is mutated in human severe combined immune deficiency. Cell 2001; 105:177-86.
47. O'Driscoll M, Cerosaletti KM, Girard PM, et al. DNA ligase IV mutations identified in patients exhibiting developmental delay and immunodeficiency. Mol Cell 2001; 8:1175-85.
48. Buck D, Malivert L, de Chasseval R, et al. Cernunnos, a novel nonhomologous end-joining factor, is mutated in human immunodeficiency with microcephaly. Cell 2006; 124:287-99.
49. Diggle CP, Bentley J, Knowles MA, Kiltie AE. Inhibition of double-strand break non-homologous end-joining by cisplatin adducts in human cell extracts. Nucleic Acids Res 2005; 33: 2531-9.
50. Ismail IH, Hendzel MJ. The gamma-H2A.X: is it just a surrogate marker of double-strand breaks or much more? Environ Mol Mutagen 2008; 49: 73-82.
51. Kaneko T, Tahara S, Matsuo M. Non-linear accumulation of 8-hydroxy-2'-deoxyguanosine, a marker of oxidized DNA damage, during aging. Mutat Res 1996; 316: 277-85.
52. Hamilton ML, Van Remmen H, Drake JA, et al. Does oxidative damage to DNA increase with age? Proc Natl Acad Sci USA 2001; 98: 10469-74.
53. Gabbita SP, Lovell MA, Markesbery WR. Increased nuclear DNA oxidation in the brain in Alzheimer's disease. J Neurochem 1998; 71: 2034-40.
54. Polidori MC, Mecocci P, Browne SE, et al. Oxidative damage to mitochondrial DNA in Huntington's disease parietal cortex. Neurosci Lett 1999; 272: 53-6.
55. Karanjawala ZE, Murphy N, Hinton DR, et al. Oxygen metabolism causes chromosome breaks and is associated with the neuronal apoptosis observed in DNA double-strand break repair mutants. Curr Biol 2002; 12: 397-402.
56. Stadelmann C, Bruck W, Bancher C, et al. Alzheimer disease: DNA fragmentation indicates increased neuronal vulnerability, but not apoptosis. J Neuropathol Exp Neurol 1998; 57: 456-64.
57. Lucassen PJ, Chung WC, Kamphorst W, Swaab DF. DNA damage distribution in the human brain as shown by in situ end labeling; area-specific differences in aging and Alzheimer disease in the absence of apoptotic morphology. J Neuropathol Exp Neurol 1997; 56: 887-900.
58. Jacobsen E, Beach T, Shen Y, et al. Deficiency of the Mre11 DNA repair complex in Alzheimer's disease brains. Brain Res Mol Brain Res 2004; 128:1-7.
59. Shackelford DA. DNA end joining activity is reduced in Alzheimer's disease. Neurobiol Aging 2006; 27: 596-605.
60. Suberbielle E, Sanchez PE, Kravitz AV, et al. Physiologic brain activity causes DNA double-strand breaks in neurons, with exacerbation by amyloid-β. Nat Neurosci 2013; 16: 613-21.
61. Ramadori G, Lee CE, Bookout AL, et al. Brain SIRT1: anatomical distribution and regulation by energy availability. J Neurosci 2008; 28: 9989-96.
62. Dobbin MM, Madabhushi R, Pan L, et al. SIRT1 collaborates with ATM and HDAC1 to maintain genomic stability in neurons. Nat Neurosci 2013; 16: 1008-15.
63. 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.
64. Donmez G, Wang D, Cohen DE, Guarente L. SIRT1 suppresses beta-amyloid production by activating the alphasecretase gene ADAM10. Cell 2010; 142: 320-32.
65. Enokido Y, Tamura T, Ito H, et al. Mutant huntingtin impairs Ku70-mediated DNA repair. J Cell Biol 2010; 189: 425-43.
66. Goehler H, Lalowski M, Stelzl U, et al. A protein interaction network links GIT1, an enhancer of huntingtin aggregation, to Huntington's disease. Mol Cell 2004; 15: 853-65.
67. Tamura T, Sone M, Iwatsubo T, et al. Ku70 alleviates neurodegeneration in Drosophila models of Huntington's disease. PLoS One 2011; 6: e27408.
68. Qi ML, Tagawa K, Enokido Y, et al. Proteome analysis of soluble nuclear proteins reveals that HMGB1/2 suppress genotoxic stress in polyglutamine diseases. Nat Cell Biol 2007; 9: 402-14.
69. Prasad R, Liu Y, Deterding LJ, et al. HMGB1 is a cofactor in mammalian base excision repair. Mol Cell 2007; 27: 829-41.
70. Lange SS, Mitchell DL, Vasquez KM. High mobility group protein B1 enhances DNA repair and chromatin modification after DNA damage. Proc Natl Acad Sci USA 2008; 105: 10320-5.
71. Stros M, Cherny D, Jovin TM. HMG1 protein stimulates DNA end joining by promoting association of DNA molecules via their ends. Eur J Biochem 2000; 267: 4088-97.
72. Goula AV, Berquist BR, Wilson DM III, et al. Stoichiometry of base excision repair proteins correlates with increased somatic CAG instability in striatum over cerebellum in Huntington's disease transgenic mice. PLoS Genet 2009; 5: e1000749.
73. Enokido Y, Yoshitake A, Ito H, Okazawa H. Age-dependent change of HMGB1 and DNA double-strand break accumulation in mouse brain. Biochem Biophys Res Commun 2008; 376: 128-33.
74. Vaz B, Halder S, Ramadan K. Role of p97/VCP (Cdc48) in genome stability. Front Genet 2013; 4: 60.
75. Meerang M, Ritz D, Paliwal S, et al. The ubiquitin-selective segregase VCP/p97 orchestrates the response to DNA double-strand breaks. Nat Cell Biol 2011; 13: 1376-82.
76. Watts GD, Wymer J, Kovach MJ, et al. Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosincontaining protein. Nat Genet 2004; 36: 377-81.
77. Jiang M, Wang J, Fu J, et al. Neuroprotective role of Sirt1 in mammalian models of Huntington's disease through activation of multiple Sirt1 targets. Nat Med 2011; 18: 153-8.
78. Jeong H, Cohen DE, Cui L, et al. Sirt1 mediates neuroprotection from mutant huntingtin by activation of the TORC1 and CREB transcriptional pathway. Nat Med 2011; 18: 159-65.
79. Houtsmuller AB, Rademakers S, Nigg AL, et al. Action of DNA repair endonuclease ERCC1/XPF in living cells. Science 1999; 284: 958-61.
80. Zhu XD, Niedernhofer L, Kuster B, et al. ERCC1/XPF removes the 3' overhang from uncapped telomeres and represses formation of telomeric DNA-containing double minute chromosomes. Mol Cell 2003; 12: 1489-98.
81. Borgesius NZ, de Waard MC, van der Pluijm I, et al. Accelerated age-related cognitive decline and neurodegeneration, caused by deficient DNA repair. J Neurosci 2011; 31: 12543-53.
82. Ahles TA, Saykin AJ. Candidate mechanisms for chemotherapy-induced cognitive changes. Nat Rev Cancer 2007; 7: 192-201.
83. Vegh MJ, de Waard MC, van der Pluijm I, et al. Synaptic proteome changes in a DNA repair deficient ercc1 mouse model of accelerated aging. J Proteome Res 2012; 11: 1855-67.
84. Lu T, Pan Y, Kao SY, et al. Gene regulation and DNA damage in the ageing human brain. Nature 2004; 429: 883-91.
85. Hetman M, Vashishta A, Rempala G. Neurotoxic mechanisms of DNA damage: focus on transcriptional inhibition. J Neurochem 2010; 114: 1537-49.
86. Charlet-Berguerand N, Feuerhahn S, Kong SE, et al. RNA polymerase II bypass of oxidative DNA damage is regulated by transcription elongation factors. EMBO J 2006; 25: 5481-91.
87. Pastoriza-Gallego M, Armier J, Sarasin A. Transcription through 8-oxoguanine in DNA repair-proficient and Csb(-)/Ogg1(-) DNA repair-deficient mouse embryonic fibroblasts is dependent upon promoter strength and sequence context. Mutagenesis 2007; 22: 343-51.
88. Pankotai T, Bonhomme C, Chen D, Soutoglou E. DNAPKcsdependent arrest of RNA polymerase II transcription in the presence of DNA breaks. Nat Struct Mol Biol 2012; 19: 276-82.
89. Shanbhag NM, Rafalska-Metcalf IU, Balane-Bolivar C, et al. ATM-dependent chromatin changes silence transcription in cis to DNA double-strand breaks. Cell 2010; 141: 970-81.
90. O'Hagan HM, Mohammad HP, Baylin SB. Double strand breaks can initiate gene silencing and SIRT1-dependent onset of DNA methylation in an exogenous promoter CpG island. PLoS Genet 2008; 4: e1000155.
91. Hanawalt PC, Spivak G. Transcription-coupled DNA repair: two decades of progress and surprises. Nat Rev Mol Cell Biol 2008; 9: 958-70.
92. Sweder KS, Hanawalt PC. Preferential repair of cyclobutane pyrimidine dimers in the transcribed strand of a gene in yeast chromosomes and plasmids is dependent on transcription. Proc Natl Acad Sci USA 1992; 89: 10696-700.
93. Christians FC, Hanawalt PC. Inhibition of transcription and strand-specific DNA repair by alpha-amanitin in Chinese hamster ovary cells. Mutat Res 1992; 274: 93-101.
94. Moses RE, O'Malley BW. DNA transcription and repair: a confluence. J Biol Chem 2012; 287: 23266-70.
95. Ju BG, Lunyak VV, Perissi V, et al. A topoisomerase IIbetamediated dsDNA break required for regulated transcription. Science 2006; 312: 1798-802.
96. Kamileri I, Karakasilioti I, Sideri A, et al. Defective transcription initiation causes postnatal growth failure in a mouse model of nucleotide excision repair (NER) progeria. Proc Natl Acad Sci USA 2012; 109: 2995-3000.
97. Niehrs C, Schafer A. Active DNA demethylation by Gadd45 and DNA repair. Trends Cell Biol 2012; 22: 220-7.
98. Schmitz KM, Schmitt N, Hoffmann-Rohrer U, et al. TAF12 recruits Gadd45a and the nucleotide excision repair complex to the promoter of rRNA genes leading to active DNA demethylation. Mol Cell 2009; 33: 344-53.
99. Hodges A, Strand AD, Aragaki AK, et al. Regional and cellular gene expression changes in human Huntington's disease brain. Hum Mol Genet 2006; 15: 965-77.
100. Luthi-Carter R, Hanson SA, Strand AD, et al. Dysregulation of gene expression in the R6/2 model of polyglutamine disease: parallel changes in muscle and brain. Hum Mol Genet 2002; 11: 1911-26.
101. Okazawa H. Polyglutamine diseases: a transcription disorder? Cell Mol Life Sci 2003; 60: 1427-39.
102. Waragai M, Lammers CH, Takeuchi S, et al. PQBP-1, a novel polyglutamine tract-binding protein, inhibits transcription activation by Brn-2 and affects cell survival. Hum Mol Genet 1999; 8: 977-87.
103. Ng CW, Yildirim F, Yap YS, et al. Extensive changes in DNA methylation are associated with expression of mutant huntingtin. Proc Natl Acad Sci USA 2013; 110: 2354-9.
104. Liu L, van Groen T, Kadish I, Tollefsbol TO. DNA methylation impacts on learning and memory in aging. Neurobiol Aging 2009; 30: 549-60.
105. Day JJ, Sweatt JD. DNA methylation and memory formation. Nat Neurosci 2010; 13: 1319-23.
106. Hevroni D, Rattner A, Bundman M, et al. Hippocampal plasticity involves extensive gene induction and multiple cellular mechanisms. J Mol Neurosci 1998; 10: 75-98.
107. Ma DK, Jang MH, Guo JU, et al. Neuronal activity-induced Gadd45b promotes epigenetic DNA demethylation and adult neurogenesis. Science 2009; 323: 1074-7.
108. Leach PT, Poplawski SG, Kenney JW, et al. Gadd45b knockout mice exhibit selective deficits in hippocampusdependent long-term memory. Learn Mem 2012; 19: 319-24.
109. Impagnatiello F, Guidotti AR, Pesold C, et al. A decrease of reelin expression as a putative vulnerability factor in schizophrenia. Proc Natl Acad Sci USA 1998; 95: 15718-23.
110. Guidotti A, Auta J, Davis JM, et al. Decrease in reelin and glutamic acid decarboxylase67 (GAD67) expression in schizophrenia and bipolar disorder: a postmortem brain study. Arch Gen Psychiatry 2000; 57: 1061-9.
111. Fatemi SH, Earle JA, McMenomy T. Reduction in Reelin immunoreactivity in hippocampus of subjects with schizophrenia, bipolar disorder and major depression. Mol Psychiatry 2000; 5: 654-63.
112. Belforte JE, Zsiros V, Sklar ER, et al. Postnatal NMDA receptor ablation in corticolimbic interneurons confers schizophrenia-like phenotypes. Nat Neurosci 2010; 13: 76-83.
113. Nakazawa K, Zsiros V, Jiang Z, et al. GABAergic interneuron origin of schizophrenia pathophysiology. Neuropharmacology 2012; 62: 1574-83.
114. Veldic M, Caruncho HJ, Liu WS, et al. DNAmethyltransferase 1 mRNA is selectively overexpressed in telencephalic GABAergic interneurons of schizophrenia brains. Proc Natl Acad Sci USA 2004; 101: 348-53.
115. Veldic M, Guidotti A, Maloku E, et al. In psychosis, cortical interneurons overexpress DNA-methyltransferase 1. Proc Natl Acad Sci U S A. 2005; 102: 2152-7.
116. Grayson DR, Guidotti A. The dynamics of DNA methylation in schizophrenia and related psychiatric disorders. Neuropsychopharmacology 2013; 38: 138-66.
117. Ha K, Lee GE, Palii SS, et al. Rapid and transient recruitment of DNMT1 to DNA double-strand breaks is mediated by its interaction with multiple components of the DNA damage response machinery. Hum Mol Genet 2011; 20: 126-40.
118. Nishioka N, Arnold SE. Evidence for oxidative DNA damage in the hippocampus of elderly patients with chronic schizophrenia. Am J Geriatr Psychiatry 2004; 12: 167-75.
119. Wang JF, Shao L, Sun X, Young LT. Increased oxidative stress in the anterior cingulate cortex of subjects with bipolar disorder and schizophrenia. Bipolar Disord 2009; 11: 523-29.
120. Do KQ, Trabesinger AH, Kirsten-Kruger M, et al. Schizophrenia: glutathione deficit in cerebrospinal fluid and prefrontal cortex in vivo. Eur J Neurosci 2000; 12: 3721-28.
121. Tosic M, Ott J, Barral S, et al. Schizophrenia and oxidative stress: glutamate cysteine ligase modifier as a susceptibility gene. Am J Hum Genet 2006; 79: 586-92.
122. Behrens MM, Sejnowski TJ. Does schizophrenia arise from oxidative dysregulation of parvalbumin-interneurons in the developing cortex? Neuropharmacology 2009; 57: 193-200.
123. Jiang Z, Cowell RM, Nakazawa K. Convergence of genetic and environmental factors on parvalbumin-positive interneurons in schizophrenia. Front Behav Neurosci 2013 3; 7: 116.
124. Behrens MM, Ali SS, Dao DN, et al. Ketamine-induced loss of phenotype of fast-spiking interneurons is mediated by NADPH-oxidase. Science 2007; 318: 1645-47.
125. Behrens MM, Ali SS, Dugan LL. Interleukin-6 mediates the increase in NADPH-oxidase in the ketamine model of schizophrenia. J Neurosci 2008; 28: 13957-66.
126. Steullet P, Cabungcal JH, Kulak A, et al. Redox dysregulation affects the ventral but not dorsal hippocampus: impairment of parvalbumin neurons, gamma oscillations, and related behaviors. J Neurosci 2010; 30: 2547-58.
127. Cabungcal JH, Steullet P, Morishita H, et al. Perineuronal nets protect fast-spiking interneurons against oxidative stress. Proc Natl Acad Sci USA 2013; 110: 9130-35.
128. Jiang Z, Rompala GR, Zhang S, et al. Social isolation exacerbates schizophrenia-like phenotypes via oxidative stress in cortical interneurons. Biol Psychiatry 2013; 73: 1024-34.
129. Malewicz M, Kadkhodaei B, Kee N, et al. Essential role for DNA-PK-mediated phosphorylation of NR4A nuclear orphan receptors in DNA double-strand break repair. Genes Dev 2011; 25: 2031-40.
130. Hawk JD, Bookout AL, Poplawski SG, et al. NR4A nuclear receptors support memory enhancement by histone deacetylase inhibitors. J Clin Invest 2012; 122: 3593-602.
131. Buervenich S, Carmine A, Arvidsson M, et al. NURR1 mutations in cases of schizophrenia and manic-depressive disorder. Am J Med Genet 2000; 96: 808-13.
132. Xing G, Zhang L, Russell S, Post R. Reduction of dopaminerelated transcription factors Nurr1 and NGFI-B in the prefrontal cortex in schizophrenia and bipolar disorders. Schizophr Res 2006; 84: 36-56.
133. Saadat M, Pakyari N, Farrashbandi H. Genetic polymorphism in the DNA repair gene XRCC1 and susceptibility to schizophrenia. Psychiatry Res 2008; 157: 241-5.
134. Psimadas D, Messini-Nikolaki N, Zafiropoulou M, et al. DNA damage and repair efficiency in lymphocytes from schizophrenic patients. Cancer Lett 2004; 204: 33-40.
135. Benes FM, Lim B, Subburaju S. Site-specific regulation of cell cycle and DNA repair in post-mitotic GABA cells in schizophrenic versus bipolars. Proc Natl Acad Sci USA 2009; 106: 11731-6.
136. Adam OR, Jankovic J. Symptomatic treatment of Huntington disease. Neurotherapeutics 2008; 5: 181-97.
137. Bonelli RM, Hofmann P. A systematic review of the treatment studies in Huntington's disease since 1990. Expert Opin Pharmacother 2007; 8: 141-53.
138. Huntington Study Group. Tetrabenazine as antichorea therapy in Huntington disease: a randomized controlled trial. Neurology 2006; 66: 366-72.
139. Ross CA, Tabrizi SJ. Huntington's disease: from molecular pathogenesis to clinical treatment. Lancet Neurol 2011; 10: 83-98.
140. Kazantsev AG, Thompson LM. Therapeutic application of histone deacetylase inhibitors for central nervous system disorders. Nat Rev Drug Discov 2008; 7: 854-68.
141. 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 USA 2003; 100: 2041-6.
142. Arzenani MK, Zade AE, Ming Y, et al. Genomic DNA hypomethylation by histone deacetylase inhibition implicates DNMT1 nuclear dynamics. Mol Cell Biol 2011; 31: 4119-28.
143. Guidotti A, Auta J, Chen Y, et al. Epigenetic GABAergic targets in schizophrenia and bipolar disorder. Neuropharmacology 2011; 60: 1007-16.
144. Kurita M, Holloway T, Garcia-Bea A, et al. HDAC2 regulates atypical antipsychotic responses through the modulation of mGlu2 promoter activity. Nat Neurosci 2012; 15: 1245-54.
145. Lee JH, Choy ML, Ngo L, et al. Histone deacetylase inhibitor induces DNA damage, which normal but not transformed cells can repair. Proc Natl Acad Sci USA 2010; 107: 14639-44.