The Eminent Role of microRNAs in the Pathogenesis of Alzheimer's Disease

Abstract

Alzheimer's disease (AD) is an irrevocable neurodegenerative condition characterized by the presence of senile plaques comprising amassed β-amyloid peptides (Aβ) and neurofibrillary tangles mainly comprising extremely phosphorylated Tau proteins. Recent studies have emphasized the role of microRNAs (miRNAs) in the development of AD. A number of miRNAs, namely, miR-200a-3p, miR-195, miR-338-5p, miR-34a-5p, miR-125b-5p, miR-132, miR-384, miR-339-5p, miR-135b, miR-425-5p, and miR-339-5p, have been shown to participate in the development of AD through interacting with BACE1. Other miRNAs might affect the inflammatory responses in the course of AD. Aberrant expression of several miRNAs in the plasma samples of AD subjects has been shown to have the aptitude for differentiation of AD subjects from healthy subjects. Finally, a number of AD-modifying agents affect miRNA profile in cell cultures or animal models. We have performed a comprehensive search and summarized the obtained data about the function of miRNAs in AD in the current review article.

Stress Granules and Neurodegenerative Disorders: A Scoping Review

“…These stresses in mammalian cells include viral infections (biotic stress), induction of redox stress with sodium arsenite, heat and UV radiation which are environmental stress conditions (Kedersha et al, 2013 ). Three groups can form the protein component of stress granules: RNA-binding proteins, translation initiation factors, and non-RNA-binding proteins (Cao et al, 2020 ; Samadian et al, 2021 ). Stoppage at the critical stage of translation initiation due to biotic or environmental stress leads to the isolation of the translating polysomes resulting in the creation of a huge reservoir of RNA and related proteins that build and increase the number of SGs.…”

microRNA Heterogeneity, Innate-Immune Defense and the Efficacy of SARS-CoV-2 Infection—A Commentary

“…Thus, the major functions of host miRNAs are: (i) In mRNA silencing; (ii) in the repression of the expression of genetic information encoded in the target mRNA of that miRNA; (iii) in the post-transcriptional regulation of gene expression, and this extends into shaping the transcriptome of the cell in both health and disease; and (iv) in playing a modulatory role in host interactions with viruses, including coronaviruses [ 6 , 13 , 34 , 44 , 46 , 47 , 48 ]. Because ssvRNA like the SARS-CoV-2 virus is also susceptible to recognition by miRNA, naturally-occurring miRNAs may function to seek out ssvRNA and neutralize their actions, thus contributing to a novel miRNA-facilitated innate-immunity in the host.…”

“…Typically generated by RNA polymerase II (RNAPII)-based transcription from genomic DNA and pre-miRNA processing mechanisms, human cells typically contain about ~2650 different miRNA species, although miRNA populations vary widely amongst different cell types and amongst individuals of the same species (miRBase v.22; GENCODE data v.29) [ 2 , 3 , 4 , 5 ]. Different cell types contain a different complement of miRNAs that vary in abundance, speciation, and complexity during development, homeostatic day-to-day function, aging, and disease [ 4 , 5 , 6 ]. Although multiple mechanisms exist, the general mode of miRNA action is to bind to the 3′-untranslated region (3’-UTR) of their target messenger RNA (mRNA) via complementary base-pair interactions; in doing so, this miRNA-mRNA hybrid: (i) Can impair or block normal mRNA transit through the cleft of the eukaryotic 80S ribosome [ 4 , 5 , 7 ]; (ii) represses gene expression post-transcriptionally by destabilizing and down-regulating their target mRNA(s) [ 1 , 3 , 4 ]; and (iii) reduce protein production and repress genetic information encoded in that target mRNA [ 1 , 2 , 3 , 4 , 5 ].…”

“…The majority of miRNA–mRNA interactions, biogenesis, and function in any human cell remain largely unidentified, poorly characterized, and incompletely understood, although rapid research progress is being made. Multiple miRNA-mRNA interactions are known to be especially important in human neurological health and disease [ 2 , 5 , 6 ]. Interestingly, as single-stranded RNAs, messenger RNA (mRNA) and single-stranded viral RNA (ssvRNA) appear to be interchangeable targets for miRNA and/or sncRNA action [ 3 , 4 , 5 , 6 , 7 , 8 ].…”

“…Multiple miRNA-mRNA interactions are known to be especially important in human neurological health and disease [ 2 , 5 , 6 ]. Interestingly, as single-stranded RNAs, messenger RNA (mRNA) and single-stranded viral RNA (ssvRNA) appear to be interchangeable targets for miRNA and/or sncRNA action [ 3 , 4 , 5 , 6 , 7 , 8 ]. That is, any single-stranded RNA or ssvRNA encountered by a host miRNA that is sufficiently complementary will be down-regulated, and its potential biological activity will be accordingly diminished.…”