Myocyte enhancing factor-2A in Alzheimer's disease: Genetic analysis and association with MEF2A-polymorphisms

González, Pelayo; Álvarez, Victoria; Menéndez, Manuel; Lahoz, Carlos H.; Martı́nez, Carmen; Corao, Ana I.; Calatayud, María Teresa Reyna; Peña, Joaquín; García-Castro, Mónica; Coto, Eliécer

doi:10.1016/j.neulet.2006.09.055

Cited by 17 publications

(18 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…STAT1 also has a role in controlling the gene expression of BACE1 , binding to its promoter region, and can be upregulated by Aβ, characterizing a positive feedback loop that could lead to the progressive increase of production and further accumulation of Aβ [ 61 – 63 ]. Regarding MEF2A, Burton et al [ 64 ] and Gonzalez et al [ 65 ] have suggested that deregulation in the control of these TF activation pathways could be associated with increased risk of developing AD. Additionally, the genes MEF2C and CELF1, identified by genome-wide association studies as having a small effect on AD risk [ 11 ], were inferred as MEF2A and YY1 targets, respectively (data not shown), which reinforces the idea that these genes are part of a broad and complex context and that to discuss their roles in the whole scenario could be a much more constructive approach.…”

Section: Discussionmentioning

confidence: 99%

Alzheimer’s disease master regulators analysis: search for potential molecular targets and drug repositioning candidates

et al. 2018

View full text Add to dashboard Cite

BackgroundAlzheimer’s disease (AD) is a multifactorial and complex neuropathology that involves impairment of many intricate molecular mechanisms. Despite recent advances, AD pathophysiological characterization remains incomplete, which hampers the development of effective treatments. In fact, currently, there are no effective pharmacological treatments for AD. Integrative strategies such as transcription regulatory network and master regulator analyses exemplify promising new approaches to study complex diseases and may help in the identification of potential pharmacological targets.MethodsIn this study, we used transcription regulatory network and master regulator analyses on transcriptomic data of human hippocampus to identify transcription factors (TFs) that can potentially act as master regulators in AD. All expression profiles were obtained from the Gene Expression Omnibus database using the GEOquery package. A normal hippocampus transcription factor-centered regulatory network was reconstructed using the ARACNe algorithm. Master regulator analysis and two-tail gene set enrichment analysis were employed to evaluate the inferred regulatory units in AD case-control studies. Finally, we used a connectivity map adaptation to prospect new potential therapeutic interventions by drug repurposing.ResultsWe identified TFs with already reported involvement in AD, such as ATF2 and PARK2, as well as possible new targets for future investigations, such as CNOT7, CSRNP2, SLC30A9, and TSC22D1. Furthermore, Connectivity Map Analysis adaptation suggested the repositioning of six FDA-approved drugs that can potentially modulate master regulator candidate regulatory units (Cefuroxime, Cyproterone, Dydrogesterone, Metrizamide, Trimethadione, and Vorinostat).ConclusionsUsing a transcription factor-centered regulatory network reconstruction we were able to identify several potential molecular targets and six drug candidates for repositioning in AD. Our study provides further support for the use of bioinformatics tools as exploratory strategies in neurodegenerative diseases research, and also provides new perspectives on molecular targets and drug therapies for future investigation and validation in AD.Electronic supplementary materialThe online version of this article (10.1186/s13195-018-0394-7) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

Alzheimer’s disease master regulators analysis: search for potential molecular targets and drug repositioning candidates

et al. 2018

View full text Add to dashboard Cite

show abstract

“…The DNAJC17 gene is a negative regulator of transcription from RNA polymerase II promoter and has been previously associated with autism in a small study (38). The MEF2A gene encodes a transcription factor and plays a key role in skeletal, cardiac, smooth muscle and neuronal cell differentiation (39). Genetic variation in MEF2A has been previously associated with formal thought disorder (40), a major feature of schizophrenia and other psychotic disorders, and Alzheimer's disease (39).…”

Section: Discussionmentioning

confidence: 99%

DNA methylation and inflammation marker profiles associated with a history of depression

Crawford

Craig

Mansell

et al. 2018

Human Molecular Genetics

View full text Add to dashboard Cite

Depression is a common and disabling disorder, representing a major social and economic health issue. Moreover, depression is associated with the progression of diseases with an inflammatory etiology including many inflammatory-related disorders. At the molecular level, the mechanisms by which depression might promote the onset of these diseases and associated immune-dysfunction are not well understood. In this study we assessed genome-wide patterns of DNA methylation in whole blood-derived DNA obtained from individuals with a self-reported history of depression (n = 100) and individuals without a history of depression (n = 100) using the Illumina 450K microarray. Our analysis identified six significant (Šidák corrected P < 0.05) depression-associated differentially methylated regions (DMRs); the top-ranked DMR was located in exon 1 of the LTB4R2 gene (Šidák corrected P = 1.27 × 10-14). Polygenic risk scores (PRS) for depression were generated and known biological markers of inflammation, telomere length (TL) and IL-6, were measured in DNA and serum samples, respectively. Next, we employed a systems-level approach to identify networks of co-methylated loci associated with a history of depression, in addition to depression PRS, TL and IL-6 levels. Our analysis identified one depression-associated co-methylation module (P = 0.04). Interestingly, the depression-associated module was highly enriched for pathways related to immune function and was also associated with TL and IL-6 cytokine levels. In summary, our genome-wide DNA methylation analysis of individuals with and without a self-reported history of depression identified several candidate DMRs of potential relevance to the pathogenesis of depression and its associated immune-dysfunction phenotype.

show abstract

“…The evidence accumulated so far indicates that the pathogeneses of the trinucleotide repeat disorders are complex and multifactorial [24,25]. Recently, it was found that the Pro279Leu mutation combined with APOEε4+ might make its carriers more likely to develop late‐onset Alzheimer’s disease [26]. Even though we performed an in vitro functional analysis of all of the typical MEF2A variants, we cannot entirely exclude the possibility that some MEF2A variants might have a disease‐causing effect in vivo , perhaps by interacting with other proteins in mammalian cells.…”

Section: Discussionmentioning

confidence: 99%

Structural changes in exon 11 of MEF2A are not related to sporadic coronary artery disease in Han Chinese population

Dai

Zhou

Xiao

et al. 2010

Eur J Clin Investigation

View full text Add to dashboard Cite

show abstract

Myocyte enhancing factor-2A in Alzheimer's disease: Genetic analysis and association with MEF2A-polymorphisms

Cited by 17 publications

References 41 publications

Alzheimer’s disease master regulators analysis: search for potential molecular targets and drug repositioning candidates

Alzheimer’s disease master regulators analysis: search for potential molecular targets and drug repositioning candidates

DNA methylation and inflammation marker profiles associated with a history of depression

Structural changes in exon 11 of MEF2A are not related to sporadic coronary artery disease in Han Chinese population

Contact Info

Product

Resources

About