MicroRNAs in neurodegenerative diseases and their therapeutic potential

Abstract

MicroRNAs (miRNAs) are abundant, endogenous, short, noncoding RNAs that act as important post-transcriptional regulators of gene expression by base-pairing with their target mRNA. During the last decade, substantial knowledge has accumulated regarding the biogenesis of miRNAs, their molecular mechanisms and functional roles in a variety of cellular contexts. Altered expression of certain miRNA molecules in the brains of patients with neurodegenerative diseases such as Alzheimer and Parkinson suggests that miRNAs could have a crucial regulatory role in these disorders. Polymorphisms in miRNA target sites may also constitute an important determinant of disease risk. Additionally, emerging evidence points to specific miRNAs targeting and regulating the expression of particular proteins that are key to disease pathogenesis. Considering that the amount of these proteins in susceptible neuronal populations appears to be critical to neurodegeneration, miRNA-mediated regulation represents a new target of significant therapeutic prospects. In this review, the implications of miRNAs in several neurodegenerative disorders and their potential as therapeutic interventions are discussed.

Aging and Alzheimer’s disease: Comparison and associations from molecular to system level

“…The essentiality of miRNAs in neuronal cells was established by conditional Dicer KO, which is an important enzyme in miRNA genesis. Conditional perturbation experiments of Dicer in mouse brain showed progressive neuronal loss associated with behavioral deficits (Junn & Mouradian, 2012). A pool of miRNAs has been found to be associated with AD at each step of AD pathology or could serve as circulating biomarkers or in diagnostics, such as downregulated miR‐132, 212 and upregulated miR‐34a and 125b(Millan, 2017; Tan, Yu, Hu, & Tan, 2013), etc.…”

Analysis of the RNA content of the exosomes derived from blood serum and urine and its potential as biomarkers

“…Neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's diseases have been the subject of several miRNA profiling studies, that used the post-mortem brain tissue and body fluids of the patients (reviewed in [10]). The analysis shows altered expression of certain miRNAs, which suggests they may have a very important regulatory role by directly or indirectly affecting development and progression of these diseases and may be used as biomarkers.…”

Loss of MicroRNA-7 Regulation Leads to α-Synuclein Accumulation and Dopaminergic Neuronal Loss In Vivo

“…Aberrant miR activity has been associated with a number of neurodegenerative diseases including PD. [25][26][27][28] In particular, miR-7 has been shown to bind to the 3'UTR of the SNCA gene and inhibit its translation. 29,30 However, the pathophysiological relevance of the miR-7 targeting of SNCA to PD remains unclear.…”