Brain microRNAs dysregulation: Implication for missplicing and abnormal post-translational modifications of tau protein in Alzheimer's disease and related tauopathies

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs that regulate post-transcriptional gene expression by targeting specific mRNAs for degradation or translation repression. Changes in miRNAs expression profiles have been reported in several neurodegenerative disorders such as Alzheimer's disease (AD) and related tauopathies, which are characterized by tau aggregation and neurofibrillary tangle formation (NFTs) in the brain. There is a fundamental challenge in determining how dysregulation of miRNAs can promote a pathological condition. Therefore, identifying the target genes of dysregulated miRNAs, signaling pathways and biological processes, as well as pathogenic factors which trigger miRNA dysregulation may be helpful for subsequent therapeutic development. This article reviews studies focused on the presently known roles of miRNAs in the regulation of alternative splicing and post-translational modifications of tau, events associated with the development of AD and related tauopathies. We hope this review will help readers understand the pathogenesis and the most recent therapeutic approaches to treat tauopathies.

Keywords: Alternative splicing; Alzheimer’s disease; Post-translational modifications; Tau protein; Tauopathies; miRNA.