Epigenetically regulated microRNAs in Alzheimer's disease

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.