<i>DNMT3A</i>
            Moderates Cognitive Decline in Subjects with Mild Cognitive Impairment: Replicated Evidence from Two Mild Cognitive Impairment Cohorts

Chouliaras, Leonidas; Kenis, Günter; Visser, Pieter Jelle; Scheltens, Philip; Tsolaki, Magda; Jones, Roy; Kehoe, Patrick Gavin; Graff, Caroline; Girtler, Nicola; Wallin, Åsa; Rikkert, Marcel G M Olde; Spiru, Luiza; Elias-Sonnenschein, Lyzel; Ramakers, Inez H.G.B.; Pishva, Ehsan; Os, Jim van; Steinbusch, Harry W.M.; Verhey, Frans R.J.; Hove, Daniël L.A. van den; Rutten, Bart P. F.

doi:10.2217/epi.15.22

Cited by 22 publications

(11 citation statements)

References 20 publications

(22 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was described elsewhere that DNMT3a and DNMT3b are essential for memory formation and that they participated in neuronal and synaptic plasticity changes. Recently, it is has been reported that DNMT3b moderates cognitive decline in subjects with mild cognitive impairment [ 41 , 42 ]. The significant changes found in Dnmt1 and Dnmt3b in young 5XFAD lead to higher cytosine methylation, prior to the development of AD hallmark in this mouse, underlying the earlier participation for methylation processed at the onset of the pathology.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic mechanisms underlying cognitive impairment and Alzheimer disease hallmarks in 5XFAD mice

Griñán-Ferré

Sarroca

Ivanova

et al. 2016

Aging

View full text Add to dashboard Cite

5XFAD is an early-onset mouse transgenic model of Alzheimer disease (AD). Up to now there are no studies that focus on the epigenetic changes produced as a result of Aβ-42 accumulation and the possible involvement in the different expression of related AD-genes. Under several behavioral and cognition test, we found impairment in memory and psychoemotional changes in female 5XFAD mice in reference to wild type that worsens with age.Cognitive changes correlated with alterations on protein level analysis and gene expression of markers related with tau aberrant phosphorylation, amyloidogenic pathway (APP, BACE1), Oxidative Stress (iNOS, Aldh2) and inflammation (astrogliosis, TNF-α and IL-6); no changes were found in non-amyloidogenic pathway indicators such as ADAM10.Epigenetics changes as higher CpG methylation and transcriptional changes in DNA methyltransferases (DNMTs) family were found. Dnmt1 increases in younger 5XFAD and Dnmt3a and b high levels in the oldest transgenic mice. Similar pattern was found with histone methyltransferases such as Jarid1a and G9a. Histone deacetylase 2 (Hdac2) or Sirt6., both related with cognition and memory, presented a similar pattern. Taken together, these hallmarks presented by the 5XFAD model prompted its use in assessing different potential therapeutic interventions based on epigenetic targets after earlier amyloid deposition.

show abstract

Section: Discussionmentioning

confidence: 99%

Epigenetic mechanisms underlying cognitive impairment and Alzheimer disease hallmarks in 5XFAD mice

Griñán-Ferré

Sarroca

Ivanova

et al. 2016

Aging

View full text Add to dashboard Cite

show abstract

“…This increase in binding, however, did not correlate with enhanced promoter methylation ( Baets and others 2015 ). Recently, a genetic study on single-nucleotide polymorphisms (SNPs) in DNMT3A revealed an association with a particular genotype in an SNP and greater cognitive decline in patients with mild cognitive impairment ( Chouliaras and others 2015 ) ( Box 1 ).…”

Section: Dnmts In Neurodegeneration and Neuropsychiatric Disordersmentioning

confidence: 99%

Neuronal DNA Methyltransferases: Epigenetic Mediators between Synaptic Activity and Gene Expression?

Bayraktar

Kreutz

2017

Neuroscientist

View full text Add to dashboard Cite

DNMT3A and 3B are the main de novo DNA methyltransferases (DNMTs) in the brain that introduce new methylation marks to non-methylated DNA in postmitotic neurons. DNA methylation is a key epigenetic mark that is known to regulate important cellular processes in neuronal development and brain plasticity. Accumulating evidence disclosed rapid and dynamic changes in DNA methylation of plasticity-relevant genes that are important for learning and memory formation. To understand how DNMTs contribute to brain function and how they are regulated by neuronal activity is a prerequisite for a deeper appreciation of activity-dependent gene expression in health and disease. This review discusses the functional role of de novo methyltransferases and in particular DNMT3A1 in the adult brain with special emphasis on synaptic plasticity, memory formation, and brain disorders.

show abstract

“…DNA methylation of CpG units by DNA methyltransferases (DNMTs) disrupts the binding of transcription factors and attracts methyl-CpG-binding domain proteins that are associated with gene silencing and chromatin compaction [ 111 ]. An association was discovered between the rs1187120 SNP in DNMT3A and annual decline in cognitive functioning, suggesting that DNMT3A moderates cognitive decline in subjects with mild cognitive impairment [ 112 ].…”

Section: Alzheimer’s Diseasementioning

confidence: 99%

Epigenetics of Aging and Alzheimer’s Disease: Implications for Pharmacogenomics and Drug Response

Cacabelos

Torrellas

2015

IJMS

109

View full text Add to dashboard Cite

Epigenetic variability (DNA methylation/demethylation, histone modifications, microRNA regulation) is common in physiological and pathological conditions. Epigenetic alterations are present in different tissues along the aging process and in neurodegenerative disorders, such as Alzheimer’s disease (AD). Epigenetics affect life span and longevity. AD-related genes exhibit epigenetic changes, indicating that epigenetics might exert a pathogenic role in dementia. Epigenetic modifications are reversible and can potentially be targeted by pharmacological intervention. Epigenetic drugs may be useful for the treatment of major problems of health (e.g., cancer, cardiovascular disorders, brain disorders). The efficacy and safety of these and other medications depend upon the efficiency of the pharmacogenetic process in which different clusters of genes (pathogenic, mechanistic, metabolic, transporter, pleiotropic) are involved. Most of these genes are also under the influence of the epigenetic machinery. The information available on the pharmacoepigenomics of most drugs is very limited; however, growing evidence indicates that epigenetic changes are determinant in the pathogenesis of many medical conditions and in drug response and drug resistance. Consequently, pharmacoepigenetic studies should be incorporated in drug development and personalized treatments.

show abstract

DNMT3A Moderates Cognitive Decline in Subjects with Mild Cognitive Impairment: Replicated Evidence from Two Mild Cognitive Impairment Cohorts

Cited by 22 publications

References 20 publications

Epigenetic mechanisms underlying cognitive impairment and Alzheimer disease hallmarks in 5XFAD mice

Epigenetic mechanisms underlying cognitive impairment and Alzheimer disease hallmarks in 5XFAD mice

Neuronal DNA Methyltransferases: Epigenetic Mediators between Synaptic Activity and Gene Expression?

Epigenetics of Aging and Alzheimer’s Disease: Implications for Pharmacogenomics and Drug Response

Contact Info

Product

Resources

About