Epigenetic Changes in Neurodegenerative Diseases

다국어 초록 (Multilingual Abstract)

Afflicted neurons in various neurodegenerative diseases generally display diverse and complex pathological fea-tures before catastrophic occurrence of massive neuronal loss at the late stages of the diseases. This complex nature of neuronal pathophysiology inevitably implicates systemwide changes in basic cellular activities such as transcriptional controls and signal cascades, and so on, as a cause. Recently, as one of these systemwide cellular changes associated with neurodegenerative diseases, epigenetic changes caused by protein toxicity have begun to be highlighted. Notably, recent advances in related techniques including next-generation sequencing (NGS) and mass spectrometry enable us to monitor changes in the post-translational modifications (PTMs) of histone proteins and to link these changes in histone PTMs to the specific transcriptional changes. Indeed, epigenetic alterations and consequent changes in neuronal transcriptome are now begun to be extensively studied in neurodegener-ative diseases including Alzheimer’s disease (AD). In this review, we will discuss details of our current understand-ings on epigenetic changes associated with two repre-sentative neurodegenerative diseases [AD and polygluta-mine (polyQ) diseases] and further discuss possible future development of pharmaceutical treatment of the diseases through modulating these epigenetic changes.

참고문헌 (Reference)

1 Oliveira, A. M., "Transgenic mice expressing an inhibitory truncated form of p300exhibit long-term memory deficits" 14 : 564-572, 2007

2 Wood, M. A., "Transgenic mice expressing a truncated form of CREB-binding protein(CBP)exhibit deficits in hippocampal synaptic plasticity and memory storage" 12 : 111-119, 2005

3 Cha, J. H, "Transcriptional signatures in Huntington’s disease" 83 : 228-248, 2007

4 Sugars, K. L., "Transcriptional abnormalities in Huntington disease" 19 : 233-238, 2003

5 Citron, B. A., "Transcription factor Sp1 dysregulation in Alzheimer's disease" 86 : 2499-2504, 2008

6 Strahl, B. D., "The language of covalent histone modifications" 403 : 41-45, 2000

7 Vaquero, A., "The constantly changing face of chromatin" 2003

8 이성배, "The cellular basis of dendrite pathology in neurodegenerative diseases" 생화학분자생물학회 50 (50): 5-11, 2017

9 Steffan, J. S., "The Huntington’s disease protein interacts with p53 and CREB-binding protein and represses transcription" 97 : 6763-6768, 2000

10 Frost, B., "Tau promotes neurodegeneration through global chromatin relaxation" 17 : 357-366, 2014

11 Vila, M., "Targeting programmed cell death in neurodegenerative diseases" 4 : 365-375, 2003

12 Oliveira, A. M., "Subregion-specific p300 conditional knockout mice exhibit long-term memory impairments" 18 : 161-169, 2011

13 Hockly, E., "Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, ameliorates motor deficits in a mouse model of Huntington’s disease" 100 : 2041-2046, 2003

14 Govindarajan, N., "Sodium butyrate improves memory function in an Alzheimer's disease mouse model when administered at an advanced stage of disease progression" 26 : 187-197, 2011

15 Bobrowska, A., "SIRT2 ablation has no effect on tubulin acetylation in brain, cholesterol biosynthesis or the progression of Huntington’s disease phenotypes in vivo" 7 : 34805-, 2012

16 Bannister, A. J., "Regulation of chromatin by histone modifications" 21 : 381-395, 2011

17 Govindarajan, N., "Reducing HDAC6 ameliorates cognitive deficits in a mouse model for Alzheimer’s disease" 5 : 52-63, 2013

18 Fischer, A., "Recovery of learning and memory after neuronal loss is associated with chromatin remodeling" 447 : 178-182, 2007

19 Klevytska, A. M., "Partial depletion of CREB-binding protein reduces life expectancy in a mouse model of Huntington disease" 69 : 396-404, 2010

20 Zhang, Z. Y., "Oral administration of histone deacetylase inhibitor MS-275 ameliorates neuroinflammation and cerebral amyloidosis and improves behavior in a mouse model" 72 : 178-185, 2013

21 Coppedè, F., "One-carbon metabolism and Alzheimers disease : focus on epigenetics" 11 : 246-260, 2010

22 Bolton, S. J., "Non-nuclear histone H1 is upregulated in neurones and astrocytes in prion and Alzheimer's diseases but not in acute neurodegeneration" 25 : 425-432, 1999

23 Gardian, G., "Neuroprotective effects of phenylbutyrate in the N171-82Q transgenic mouse model of Huntington’s disease" 280 : 556-563, 2005

24 Forman, M. S., "Neurodegenerative diseases : a decade of discoveries paves the way for therapeutic breakthroughs" 10 : 1055-1063, 2004

25 Cong, S. Y., "Mutant huntingtin represses CBP, but not p300, by binding and protein degradation" 30 : 560-571, 2005

26 Stack, E. C., "Modulation of nucleosome dynamics in Huntington’s disease" 16 : 1164-1175, 2007

27 Oliveira, J. M., "Mitochondrial-dependent Ca2+ handling in Huntington’s disease striatal cells : Effect of histone deacetylase inhibitors" 26 : 11174-11186, 2006

28 Schon, E. A., "Mitochondria : the next(neurode)generation" 70 : 1033-1053, 2011

29 Sadri-Vakili, G., "Mechanisms of disease : Histone modifications in Huntington's disease" 2 : 330-338, 2006

30 Agis-Balboa, R. C., "Loss of HDAC5 impairs memory function : implications for Alzheimer’s disease" 33 : 35-44, 2013

31 Giralt, A., "Long-term memory deficits in Huntington’s disease are associated with reduced CBP histone acetylase activity" 21 : 1203-1216, 2012

32 Nucifora, F. C.Jr., "Interference by huntingtin and atrophin-1 with cbp-mediated transcription leading to cellular toxicity" 291 : 2423-2428, 2001

33 Kilgore, M., "Inhibitors of class1histone deacetylases reverse contextual memory deficits in a mouse model of Alzheimers disease" 35 : 870-880, 2010

34 Pallos, J., "Inhibition of specific HDACs and sirtuins suppresses pathogenesis in a Drosophila model of Huntington’s disease" 17 : 3767-3775, 2008

35 Igarashi, S., "Inducible PC12 cell model of Huntington’s disease shows toxicity and decreased histone acetylation" 14 : 565-568, 2003

36 Blalock, E. M., "Incipient Alzheimer's disease : microarray correlation analyses reveal major transcriptional and tumor suppressor responses" 101 : 2173-2178, 2004

37 Zuccato, C., "Huntingtin interacts with REST/NRSF to modulate the transcription of NRSE-controlled neuronal genes" 35 : 76-83, 2003

38 Li, H., "Huntingtin aggregate-associated axonal degeneration is an early pathological event in Huntington’s disease mice" 21 : 8473-8481, 2001

39 Sadri-Vakili, G., "Histones associated with downregulated genes are hypoacetylated in Huntington’s disease models" 16 : 1293-1306, 2007

40 Bahari-Javan, S., "Histoneacetylation : a link between Alzheimer's disease and posttraumatic stress disorder?" 8 : 160-, 2014

41 Ferrante, R. J., "Histone deacetylase inhibition by sodium butyrate chemotherapy ameliorates the neurodegenerative phenotype in Huntington’s disease mice" 23 : 9418-9427, 2003

42 Ding, H., "Histone deacetylase 6 interacts with the microtubule-associated protein tau" 106 : 2119-2130, 2008

43 Barrett, R. M., "Hippocampal focal knockout of CBP affects specific histone modifications, long-term potentiation, and long-term memory" 36 : 1545-1556, 2011

44 Bobrowska, A., "Hdac6 knock-out increases tubulin acetylation but does not modify disease progression in the R6/2 mouse model of Huntington’s disease" 6 : 20696-, 2011

45 Coppieters, N., "Global changes in DNA methylation and hydroxymethylation in Alzheimer's disease human brain" 35 : 1334-1344, 2014

46 Koldamova, R., "Genome-wide approaches reveal EGR1-controlled regulatory networks associated with neurodegeneration" 63 : 107-114, 2014

47 Moumne, L., "Genetic knock-down of HDAC3 does not modify disease related phenotypes in a mouse model of Huntingtons disease" 7 : 31080-, 2012

48 Ng, C. W., "Extensive changes in DNA methylation are associated with expression of mutant huntingtin" 110 : 2354-2359, 2013

49 Egger, G., "Epigenetics in human disease and prospects for epigenetic therapy" 429 : 457-463, 2004

50 Hendrickx, A., "Epigenetic regulations of immediate early genes expression involved in memory formation by the amyloidprecursor protein of Alzheimer disease" 9 : 99467-, 2014

51 Jaenisch, R., "Epigenetic regulation of gene expression : How the genome integrates intrinsic and environmental signals" 33 : 245-254, 2003

52 Glajch, K. E., "Epigenetic mechanisms involved in huntington's disease pathogenesis" 4 : 1-15, 2015

53 Bradley-Whitman, M. A., "Epigenetic changes in the progression of Alzheimer's disease" 134 : 486-495, 2013

54 Ogawa, O., "Ectopic localization of phosphorylated histone H3 in Alzheimer’s disease : a mitotic catastrophe?" 105 : 524-528, 2003

55 Francis, Y. I., "Dysregulation of histone acetylation in the APP/PS1 mouse model of Alzheimer’s disease" 18 : 131-139, 2009

56 Hwang, S., "Drosophila DJ-1 decreases neural sensitivity to stress by negatively regulating Daxx-like protein through dFOXO" 9 : 1003412-, 2013

57 Gunawardena, S., "Disruption of axonal transport by loss of huntingtin or expression of pathogenic polyQ proteins in Drosophila" 40 : 25-40, 2003

58 Gunawardena, S., "Disruption of axonal transport and neuronal viability by amyloid precursor protein mutations in Drosophila" 32 : 389-401, 2001

59 Bates, E. A., "Differential contributions of Caenorhabditis elegans histone deacetylases to huntingtin polyglutamine toxicity" 26 : 2830-2838, 2006

60 Jiang, H., "Depletion of CBP is directly linked with cellular toxicity caused by mutant huntingtin" 23 : 543-551, 2006

61 Lim, S., "D-beta-hydroxybutyrate is protective in mouse models of Huntingtons disease" 6 : 24620-, 2011

62 Condliffe, D., "Cross-region reduction in 5-hydroxymethylcytosine in Alzheimer's disease brain" 35 : 1850-1854, 2014

63 Chouliaras, L., "Consistent decrease in global DNA methylation and hydroxymethylation in the hippocampus of Alzheimer's disease patients" 34 : 2091-2099, 2013

64 Gjoneska, E., "Conserved epigenomic signals in mice and humans reveal immune basis of Alzheimer's disease" 518 : 365-369, 2015

65 Chiu, C. T., "Combined treatment with the mood stabilizers lithium and valproate produces multiple beneficial effects in transgenic mouse models of Huntington’s disease" 36 : 2406-2421, 2011

66 McCampbell, A., "CREB-binding protein sequestration by expanded polyglutamine" 9 : 2197-2202, 2000

67 Chen, G., "CREB binding protein is required for both short-term and long-term memory formation" 30 : 13066-13077, 2010

68 Korzus, E., "CBP histone acetyltransferase activity is a critical component of memory consolidation" 42 : 961-972, 2004

69 Britton, L. M., "Breaking the histone code with quantitative mass spectrometry" 8 : 631-643, 2011

70 Snowdon, D. A., "Brain infarction and the clinical expression of Alzheimer’s disease" 277 : 813-817, 1997

71 Wirths, O., "Axonopathy in an APP/PS1 transgenic mouse model of Alzheimers disease" 111 : 312-319, 2006

72 Stokin, G. B., "Axonopathy and transport deficits early in the pathogenesis of Alzheimer’s diseases" 307 : 1282-1288, 2005

73 Gräff, J., "An epigenetic blockade of cognitive functions in the neurodegenerating brain" 483 : 222-226, 2012

74 Robakis, N. K., "An Alzheimer's disease hypothesis based on transcriptional dysregulation" 10 : 80-85, 2003

75 Fischer, L. R., "Amyotrophic lateral sclerosis is a distal axonopathy : evidence in mice and man" 185 : 232-240, 2004

76 Mangialasche, F., "Alzheimer’s disease : clinical trials and drug development" 9 : 702-716, 2010

77 Maurice, T., "Altered memory capacities and response to stress in p300/CBPassociated factor(PCAF)histone acetylase knockout mice" 33 : 1584-1602, 2008

78 Ho, L., "Altered expression of a-type but not b-type synapsin isoform in the brain of patients at high risk for Alzheimer's disease assessed by DNA microarray technique" 298 : 191-194, 2001

79 Boutell, J. M., "Aberrant interactions of transcriptional repressor proteins with the Huntington’s disease gene product, huntingtin" 8 : 1647-1655, 1999

80 Wood, M. A., "A transcription factor-binding domain of the coactivator CBP is essential for long-term memory and the expression of specific target genes" 13 : 609-617, 2006

81 Thomas, B., "A novel method for detecting 7-methyl guanine reveals aberrant methylation levels in Huntington disease" 436 : 112-120, 2013

82 Felsenfeld, G., "A brief history of epigenetics" 6 : 018200-, 2014