Epigenomics of Alzheimer's Disease

Cacabelos, Ramón; Torrellas, Clara; López-Muñoz, Francisco

doi:10.1016/j.jecm.2014.03.010

Cited by 20 publications

(30 citation statements)

References 181 publications

(115 reference statements)

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“…Both hypermethylation and hypomethylation of DNA, chomatin changes and miRNA dysregulation are common in age-related disorders and in multiple modalities of brain disorders [9,[15][16][17]. Altered DNA methylation patterns may account for phenotypic changes associated with human aging.…”

Section: Brain Disordersmentioning

confidence: 99%

“…A growing body of information suggests that diverse epigenetic phenomena may be involved in the pathogenesis of AD; however, this field is still in a very primitive stage [9,15,16,[34][35][36][37][38].…”

Section: Pathogenesismentioning

confidence: 99%

“…Histone modifications are present in AD [9,15,16,63,73] ; (ix) nuclear translocation of EP300 interacting inhibitor of differentiation 1 (EID1), a CBP/p300 inhibitory protein, is increased in the cortical neurons of AD patients, and overexpression of EID1 is reported to reduce hippocampal LTP and to impair cognitive function via inhibiting CBP/p300 acetyl trasferase activity and disrupting neuronal structure [83]; (x) memory formation leads to a transient increase in acetylation on lysine residues within H2B, H3, H4 [84,85]; (xi) inhibition of HDAC induces dendritic sprouting, increases synaptic number, and improves long-term memory [86]; (xii) overexpression of neuronal HDAC2 decreases dendritic spine density, synapse number, synaptic plasticity and memory formation, and HDAC2 deficiency increases synapse number and memory facilitation [87,88]; (xiii) HDAC4 is involved in learning and synaptic plasticity, and selective inhibition of HDAC4 activity may deteriorate learning and memory [89]; (xiv) treatment of hippocampal neurons with HDAC inhibitors facilitates Bdnf expression via hyper acetylation of histones at the Bdnf promoters [90,91]; (xv) histone(H3K4) methylation participates in the regulation of Bdnf expression and memory formation [92]; (xvi) histone methylation also facilitates memory consolidation coupled with histone acetylation; inhibition of HDACs with sodium butyrate (NaB) causes an increase in H3K4 trimethylation and a decrease in H3K9 dimethylation in the hippocampus after fear conditioning [92]; (xvii) histone H3 acetylation, methylation and phosphorylation is increased in the prefrontal cortex of Tg2576 mice, and histone H4 acetylation is increased in the hippocampal CA1 neurons of these transgenic mice [15,16,93].…”

Section: Histone Modificationsmentioning

confidence: 99%

“…Epigenetic changes are also determinant in several neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease or Huntington's disease [9,15,16,31,32]. …”

Section: 2mentioning

confidence: 99%

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Epigenetics of Brain Disorders: The Paradigm of Alzheimer ’s Disease

Cacabelos¹

2016

J Alzheimers Dis Parkinsonism

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Over 80% of brain disorders are associated with multiple genomic defects in conjunction with environmental factors and epigenetic phenomena. Classical epigenetic mechanisms, including DNA methylation, histone modifications, and microRNAs (miRNAs) regulation, are among the major regulatory elements that control metabolic pathways at the molecular level, with epigenetic modifications controlling gene expression transcriptionally and miRNAs suppressing gene expression post-transcriptionally. Epigenetic modifications are related to disease development, environmental exposure, drug treatment and aging. Epigenetic changes are reversible and can be potentially targeted by pharmacological intervention. Both hypermethylation and hypomethylation of DNA, chomatin changes and miRNA dysregulation are common in age-related disorders and in many neuropsychiatric, neurodevelopmental and neurodegenerative disorders. Major epigenetic mechanisms may contribute to Alzheimer's disease (AD) pathology. Several pathogenic genes and many other AD-related susceptibility genes contain methylated CpG sites. AD brains exhibit a genome-wide decrease in DNA methylation. Pathogenic histone modifications are present in AD. Alterations in epigentically regulated miRNAs may contribute to the abnormal expression of pathogenic genes in AD. Epigenetic drugs can reverse epigenetic changes in gene expression and might open future avenues in AD therapeutics. Individual differences in drug response are associated with genetic and epigenetic variability and disease determinants. Pharmacoepigenomics deals with the influence that epigenetic alterations may exert on genes involved in the pharmacogenomic network (pathogenic, mechanistic, metabolic, transporter, and pleiotropic genes) responsible for the pharmacokinetics and pharmacodynamics of drugs (efficacy and safety), as well as the effects that drugs may have on the epigenetic machinery. family), AID/APOBEC family, and the VER glycosylase family [9]. Histone acetylation is achieved by histone acetyltransferase (HAT); and histone deacetylation is produced by histone deacetylases (HDACs) (class I: HDAC1, 2, 3, and 8; class IIa: HDAC4, 5,7, and 9; class IIb: HDAC6 and 10; class III: SIRT1, 2, 6, 7; class IV: HDAC11) [9].Long non-coding (lnc) RNAs are non-protein-coding RNAs, distinct from housekeeping RNAs (tRNAs, rRNAs, and snRNAs) and independent from small RNAs with specific molecular processing machinery. Over 95% of the eukaryotic genome is transcribed into non-coding RNAs and less than 5% is translated. LncRNA-mediated epigenetic regulation depends on lcnRNA interactions with proteins or genomic DNA via RNA secondary structures [10].Epigenomic modifications are involved in a great variety of physiological and pathological conditions; of major importance are those related with major problems of health such as cardiovascular disorders, obesity, cancer, inflammatory processes, and brain disorders [11,12]. A good paradigm on the influence of epigenetic factors on human pathology is the oncogenic ...

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Section: Brain Disordersmentioning

confidence: 99%

Section: Pathogenesismentioning

confidence: 99%

Section: Histone Modificationsmentioning

confidence: 99%

“…Epigenetic changes are also determinant in several neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease or Huntington's disease [9,15,16,31,32]. …”

Section: 2mentioning

confidence: 99%

See 2 more Smart Citations

Epigenetics of Brain Disorders: The Paradigm of Alzheimer ’s Disease

Cacabelos¹

2016

J Alzheimers Dis Parkinsonism

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“…The concept of epigenetics, introduced by Conrad Waddington in 1942, and its spectacular evolution, from a biotechnological perspective, has been of great help for the past 10 years in the understanding of gene regulation and expression (functional genomics), neurogenomics, and pathogenetics of CNS disorders [3][4][5][6][7].…”

mentioning

confidence: 99%

Neuroepigenetics: Prospects and Illusions

Cacabelos¹

2017

J Clin Epigenet

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Preparation of Boronic Acid‐Functionalized Silica Nanocomposites for Selective Enrichment of Glycoproteins

Yang

Tian

Xie

et al. 2019

Chemistry & Biodiversity

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A facile method was developed for synthesis of boronic acid-functionalized silica nanocomposites (SiO 2 -BA) by 'thiol-ene' click reaction, where silica nanoparticles were synthesized by using tetraethoxysilane (TEOS) and γmercaptopropyl trimethoxysilane (γ-MPTS) as precursors. The morphology and structure properties of the resultant SiO 2 -BA were characterized by transmission electronic microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), and Brunner-Emmet-Teller measurements (BET). The adsorption behavior of the SiO 2 -BA for glycoproteins was evaluated. Under the optimized conditions, the SiO 2 -BA exhibited higher adsorption capacity towards glycoproteins (ovalbumin, OVA, 7.64 μmol/g) than non-glycoproteins (bovine serum albumin, BSA, 0.83 μmol/g). In addition, the practicality of the SiO 2 -BA was further assessed by selective enrichment of glycoproteins from egg white samples.

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Epigenomics of Alzheimer's Disease

Cited by 20 publications

References 181 publications

Epigenetics of Brain Disorders: The Paradigm of Alzheimer ’s Disease

Epigenetics of Brain Disorders: The Paradigm of Alzheimer ’s Disease

Neuroepigenetics: Prospects and Illusions

Preparation of Boronic Acid‐Functionalized Silica Nanocomposites for Selective Enrichment of Glycoproteins

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