The effect of DNA methylation on β-amyloid accumulation in Alz-heimer’s disease
Received date: 2013-11-01
Revised date: 2012-12-25
Online published: 2014-03-20
DNA methylation is the most intensively studied mechanism for epigenetic gene regulation. The functions of DNA methylation have recently drawn wide attention for investigation into the etiology of neurodegenerative disorders such as Alzheimer’s disease (AD). It has been well established that β-amyloid (Aβ) accumulation leads to the formation of senile plaques, which is a hallmark of AD pathology. Aggregation of Aβ induces neurotoxicities manifested by apoptosis, neuroin-flammation, oxidative stress and mitochondrial dysfunction etc., which consequently provoke the pathological progression of AD. Previous studies have demonstrated that DNA methylation plays an important role in regulating genes associated with the production, clearance and aggregation of Aβ. DNA methylation is a reversible process, making it a promising target for AD therapeutics. Further studies of DNA methylation in the initiation and progression of AD would pave the road to explore improved approaches to treat this disease. In this review, we summarize the involvement of DNA methylation in Aβ accumulation as well as the associated pathological alterations during the initiation and progression of AD, which would help to fully appreciate the molecular basis of AD.
Key words： DNA methylation; beta-amyloid; Alzheimer’s disease (AD)
Yushuang Deng, Gang Yu . The effect of DNA methylation on β-amyloid accumulation in Alz-heimer’s disease[J]. Hereditas(Beijing), 2014 , 36(4) : 295 -300 . DOI: 10.3724/SP.J.1005.2014.0295
[1] Wenk GL. Neuropathologic changes in Alzheimer's dis-ease. J Clin Psychiatry, 2003, 64(Suppl.9): 7–10. <\p>
[2] Irier HA, Jin P. Dynamics of DNA methylation in aging and Alzheimer's disease. DNA Cell Biol, 2012, 31(Suppl. 1): S42–S48. <\p>
[3] Ramser EM, Gan KJ, Decker H, Fan EY, Suzuki MM, Ferreira ST, Silverman MA. Amyloid–beta oligomers in-duce tau–independent disruption of BDNF axonal trans-port via calcineurin activation in cultured hippocampal neurons. Mol Biol Cell, 2013, 24(16): 2494–2505. <\p>
[4] Hardy JA, Higgins GA. Alzheimer's disease: the amyloid cascade hypothesis. Science, 1992, 256(5054): 184–185. <\p>
[5] Resende R, Marques SCF, Ferreiro E, Simöes I, Oliveira CR, Pereira CMF. Effect of alphasynuclein on amy-loid beta–induced toxicity: relevance to Lewy body variant of Alzheimer disease. Neurochem Res, 2013, 38(4): 797–806. <\p>
[6] Caesar I, Jonson M, Nilsson KPR, Thor S, Hammarström P. Curcumin promotes A–beta fibrillation and reduces neurotoxicity in transgenic Drosophila. PLoS ONE, 2012, 7(2): e31424. <\p>
[7] Rutten BP, Hammels C, Geschwind N, Menne–Lothmann C, Pishva E, Schruers K, van den Hove D, Kenis G, van Os J, Wichers M. Resilience in mental health: linking psy-chological and neurobiological perspectives. Acta Psy-chiatr Scand, 2013, 128(1): 13–20. <\p>
[8] Sherrington R, Rogaev EI, Liang Y, Rogaeva EA, Levesque G, Ikeda M, Chi H, Lin C, Li G, Holman K, Tsuda T, Mar L, Foncin JF, Bruni AC, Montesi MP, Sorbi S, Rainero I, Pinessi L, Nee L, Chumakov I, Pollen D, Brookes A, Sanseau P, Polinsky RJ, Wasco W, Da Silva HA, Haines JL, Perkicak–Vance MA, Tanzi RE, Roses AD, Fraser PE, Rommens JM, St George–Hyslop PH. Cloning of a gene bearing missense mutations in early–onset familial Alzheimer's disease. Nature, 1995, 375(6534): 754–760. <\p>
[9] Ringman JM, Coppola G. New genes and new insights from old genes: update on Alzheimer disease. Continuum (Minneap Minn), 2013, 19(2 Dementia): 358–371. <\p>
[10] Goldberg AD, Allis CD, Bernstein E. Epigenetics: a land-scape takes shape. Cell, 2007, 128(4): 635–638. <\p>
[11] Weng YL, An R, Shin J, Song HJ, Ming GL. DNA modi-fications and neurological disorders. Neurotherapeutics, 2013, 10(4): 556–567. <\p>
[12] Mastroeni D, Grover A, Delvaux E, Whiteside C, Coleman PD, Rogers J. Epigenetic changes in Alzheimer's disease: decrements in DNA methylation. Neurobiol Aging, 2010, 31(12): 2025–2037. <\p>
[13] Wang SC, Oelze B, Schumacher A. Age–specific epige-netic drift in late–onset Alzheimer's disease. PLoS ONE, 2008, 3(7): e2698. <\p>
[14] West RL, Lee JM, Maroun LE. Hypomethylation of the amyloid precursor protein gene in the brain of an Alz-heimer's disease patient. J Mol Neurosci, 1995, 6(2): 141–146. <\p>
[15] Tohgi H, Utsugisawa K, Nagane Y, Yoshimura M, Genda Y, Ukitsu M. 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, 1999, 70(2): 288–292. <\p>
[16] Barrachina M, Ferrer I. DNA methylation of Alzheimer disease and tauopathy-related genes in postmortem brain. J Neuropathol Exp Neurol, 2009, 68(8): 880–891. <\p>
[17] Arlt S, Schwedhelm E, Kölsch H, Jahn H, Linnebank M, Smulders Y, Jessen F, Böger RH, Popp J. Dimethylarginines, homocysteine metabolism, and cerebrospinal fluid markers for Alzheimer's disease. J Alzheimers Dis, 2012, 31(4): 751–758. <\p>
[18] Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D'Agostino RB, Wilson PW, Wolf PA. Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. N
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