Epigenetically regulated microRNAs in Alzheimer's disease.
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.
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.
Daniel L
DL
Van den Hove
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.
Konstantinos
K
Kompotis
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.
Roy
R
Lardenoije
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.
Gunter
G
Kenis
Institute of Psychiatry, King's College London, London, UK; Exeter Medical School, Exeter University, London, UK.
Jonathan
J
Mill
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.
Harry W
HW
Steinbusch
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.
Klaus-Peter
KP
Lesch
Center for Neuroscience, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, the Netherlands.
Carlos P
CP
Fitzsimons
VIB Center for the Biology of Disease, VIB, Leuven, Belgium; Center for Human Genetics, University of Leuven School of Medicine, Leuven, Belgium.
Bart
B
De Strooper
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.
Bart P F
BP
Rutten
D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation / Q000235:genetics; D044127:Epigenesis, Genetic / Q000235:genetics*; D006657:Histones / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009457:Neuroglia / Q000473:pathology; D009474:Neurons / Q000473:pathology; D014158:Transcription, Genetic / Q000235:genetics
D006657:Histones; D035683:MicroRNAs
Alzheimer's disease; DNA methylation; Epigenetics; MicroRNAs