The neurobiology of non-coding RNAs and Alzheimer's disease pathogenesis: Pathways, mechanisms and translational opportunities

In the past two decades, advances in sequencing technology and analysis of the human and mouse genome have led to the discovery of many non-protein-coding RNAs (ncRNAs) including: microRNA, small-interfering RNAs, piwi-associated small RNAs, transfer RNA-derived small RNAs, long-non-coding RNAs and circular RNAs. Compared with healthy controls, levels of some ncRNAs are significantly altered in the central nervous system and blood of patients affected by neurodegenerative disorders like Alzheimer's disease (AD). Although the mechanisms are still not fully elucidated, studies have revealed that these highly conserved ncRNAs are important modulators of gene expression, amyloid-β production, tau phosphorylation, inflammation, synaptic plasticity and neuronal survival, all features considered central to AD pathogenesis. Despite considerable difficulties due to their large heterogeneity, and the complexity of their regulatory pathways, research in this rapidly growing field suggests that ncRNAs hold great potential as biomarkers and therapeutic targets against AD. Herein, we summarize the current knowledge regarding the neurobiology of ncRNA in the context of AD pathophysiology.