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Neurobiol Aging. 2014 Apr;35(4):731-45. doi: 10.1016/j.neurobiolaging.2013.10.082. Epub 2013 Oct 18.

Epigenetically regulated microRNAs in Alzheimer's disease.

Author information

1
School for Mental Health and Neuroscience (MHeNS), Faculty of Health, Medicine, and Life Sciences, European Graduate School of Neuroscience (EURON), Maastricht University Medical Centre, Maastricht, the Netherlands; Division of Molecular Psychiatry, Department of Psychiatry, Psychosomatics, and Psychotherapy, University of Würzburg, Würzburg, Germany. Electronic address: d.vandenhove@maastrichtuniversity.nl.
2
School for Mental Health and Neuroscience (MHeNS), Faculty of Health, Medicine, and Life Sciences, European Graduate School of Neuroscience (EURON), Maastricht University Medical Centre, Maastricht, the Netherlands.
3
Institute of Psychiatry, King's College London, London, UK; Exeter Medical School, Exeter University, London, UK.
4
School for Mental Health and Neuroscience (MHeNS), Faculty of Health, Medicine, and Life Sciences, European Graduate School of Neuroscience (EURON), Maastricht University Medical Centre, Maastricht, the Netherlands; Division of Molecular Psychiatry, Department of Psychiatry, Psychosomatics, and Psychotherapy, University of Würzburg, Würzburg, Germany.
5
Center for Neuroscience, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, the Netherlands.
6
VIB Center for the Biology of Disease, VIB, Leuven, Belgium; Center for Human Genetics, University of Leuven School of Medicine, Leuven, Belgium.

Abstract

Alzheimer's disease (AD) is a complex neurodegenerative disorder involving dysregulation of many biological pathways at multiple levels. Classical epigenetic mechanisms, including DNA methylation and histone modifications, and regulation by microRNAs (miRNAs), are among the major regulatory elements that control these pathways at the molecular level, with epigenetic modifications regulating gene expression transcriptionally and miRNAs suppressing gene expression posttranscriptionally. Epigenetic mechanisms and miRNAs have recently been shown to closely interact with each other, thereby creating reciprocal regulatory circuits, which appear to be disrupted in neuronal and glial cells affected by AD. Here, we review those miRNAs implicated in AD that are regulated by promoter DNA methylation and/or chromatin modifications and, which frequently direct the expression of constituents of the epigenetic machinery, concluding with the delineation of a complex epigenetic-miRNA regulatory network and its alterations in AD.

KEYWORDS:

Alzheimer's disease; DNA methylation; Epigenetics; MicroRNAs

[Indexed for MEDLINE]

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