microRNAs as neuroregulators, biomarkers and therapeutic agents in neurodegenerative diseases

Abstract

The last decade has experienced the emergence of microRNAs as a key molecular tool for the diagnosis and prognosis of human diseases. Although the focus has mostly been on cancer, neurodegenerative diseases present an exciting, yet less explored, platform for microRNA research. Several studies have highlighted the significance of microRNAs in neurogenesis and neurodegeneration, and pre-clinical studies have shown the potential of microRNAs as biomarkers. Despite this, no bona fide microRNAs have been identified as true diagnostic or prognostic biomarkers for neurodegenerative disease. This is mainly due to the lack of precisely defined patient cohorts and the variability within and between individual cohorts. However, the discovery that microRNAs exist as stable molecules at detectable levels in body fluids has opened up new avenues for microRNAs as potential biomarker candidates. Furthermore, technological developments in microRNA biology have contributed to the possible design of microRNA-mediated disease intervention strategies. The combination of these advancements, with the availability of well-defined longitudinal patient cohort, promises to not only assist in developing invaluable diagnostic tools for clinicians, but also to increase our overall understanding of the underlying heterogeneity of neurodegenerative diseases. In this review, we present a comprehensive overview of the existing knowledge of microRNAs in neurodegeneration and provide a perspective of the applicability of microRNAs as a basis for future therapeutic intervention strategies.

Salivary microR‐153 and microR‐223 Levels as Potential Diagnostic Biomarkers of Idiopathic Parkinson's Disease

“…MicroRNAs (miRNAs) have emerged as key players in development, normal aging, and disease, including PD . MiRNAs are short, noncoding RNA species that act in posttranscriptional regulation of messenger RNA (mRNA) by binding the 3’ untranslated region and blocking translation.…”

MotomiRs: miRNAs in Motor Neuron Function and Disease

“…The stability of miRNAs in biofluids, dysregulation in disease and their mature detection technologies make them suitable for diagnosis, disease classification and progression, and evaluation of drug effectiveness, among others. The fact that miRNAs regulate the vast majority of the transcriptome has led to the development of nanocapsules for tissue-specific delivery of miRNAs mimics and antisense oligonucleotides (anti-miRNAs) with specific targets, converting miRNAs into an attractive option for disease intervention strategies (Basak et al, 2016). Of the MotomiRs described in this review, miR-9, miR-206, miR-183 and miR-375 could potentially be explored as biomarkers and therapeutic targets for SMA and ALS, while miR-183 and miR-375 may be contributing to the specificity of SMA detection.…”

MicroRNAs as regulators of cell death mechanisms in amyotrophic lateral sclerosis

“…Approaches for miRNA modulation include (a) substitution of down‐regulated miRNAs with synthetic miRNA mimics, which act at the gene‐level inhibiting translation, (b) up‐regulated miRNA blockade and degradation through antisense oligonucleotides (anti‐miRs) and antagomirs, (c) de‐repression of miRNA target genes through miRNA masks, which bind to the 3′UTR of mRNA, hiding the miRNA binding site, and (d) alteration of miRNA expression at the transcription level using small drug inhibitors …”