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      Role of miRNAs in Alzheimer’s Disease and Possible Fields of Application

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          Abstract

          miRNAs (or microRNAs) are a class of single-stranded RNA molecules, responsible for post-transcriptional gene silencing through binding to the coding region as well as 3′ and 5′ untranslated region of target genes. About 70% of experimentally detectable miRNAs are expressed in the brain and some studies suggest that miRNAs are intimately involved in synaptic function and in specific signals during memory formation. More and more evidence demonstrates the possible involvement of miRNAs in Alzheimer’s disease (AD). AD is the most common form of senile dementia, a disease that affects memory and cognitive functions. It is a neurodegenerative disorder characterized by loss of synapses, extracellular amyloid plaques composed of the amyloid-β peptide (Aβ), and intracellular aggregates of hyperphosphorylated TAU protein. This review aims to provide an overview of the in vivo studies of the last 5 years in the literature describing the role of the different miRNAs involved in AD. miRNAs hold huge potential as diagnostic and prognostic biomarkers and, at the same time, their modulation could be a potential therapeutic strategy against AD.

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          Most cited references81

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          Nuclear export of microRNA precursors.

          MicroRNAs (miRNAs), which function as regulators of gene expression in eukaryotes, are processed from larger transcripts by sequential action of nuclear and cytoplasmic ribonuclease III-like endonucleases. We show that Exportin-5 (Exp5) mediates efficient nuclear export of short miRNA precursors (pre-miRNAs) and that its depletion by RNA interference results in reduced miRNA levels. Exp5 binds correctly processed pre-miRNAs directly and specifically, in a Ran guanosine triphosphate-dependent manner, but interacts only weakly with extended pre-miRNAs that yield incorrect miRNAs when processed by Dicer in vitro. Thus, Exp5 is key to miRNA biogenesis and may help coordinate nuclear and cytoplasmic processing steps.
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            Control of translation and mRNA degradation by miRNAs and siRNAs.

            The control of translation and mRNA degradation is an important part of the regulation of gene expression. It is now clear that small RNA molecules are common and effective modulators of gene expression in many eukaryotic cells. These small RNAs that control gene expression can be either endogenous or exogenous micro RNAs (miRNAs) and short interfering RNAs (siRNAs) and can affect mRNA degradation and translation, as well as chromatin structure, thereby having impacts on transcription rates. In this review, we discuss possible mechanisms by which miRNAs control translation and mRNA degradation. An emerging theme is that miRNAs, and siRNAs to some extent, target mRNAs to the general eukaryotic machinery for mRNA degradation and translation control.
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              The role of apolipoprotein E in Alzheimer's disease.

              The epsilon4 allele of apolipoprotein E (APOE) is the major genetic risk factor for Alzheimer's disease (AD). Although there have been numerous studies attempting to elucidate the underlying mechanism for this increased risk, how apoE4 influences AD onset and progression has yet to be proven. However, prevailing evidence suggests that the differential effects of apoE isoforms on Abeta aggregation and clearance play the major role in AD pathogenesis. Other potential mechanisms, such as the differential modulation of neurotoxicity and tau phosphorylation by apoE isoforms as well as its role in synaptic plasticity and neuroinflammation, have not been ruled out. Inconsistent results among studies have made it difficult to define whether the APOE epsilon4 allele represents a gain of toxic function, a loss of neuroprotective function, or both. Therapeutic strategies based on apoE propose to reduce the toxic effects of apoE4 or to restore the physiological, protective functions of apoE.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                15 August 2019
                August 2019
                : 20
                : 16
                : 3979
                Affiliations
                IRCCS Centro Neurolesi “Bonino-Pulejo”, Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy
                Author notes
                [* ]Correspondence: emanuela.mazzon@ 123456irccsme.it ; Tel.: +39-090-6012-8172
                Author information
                https://orcid.org/0000-0002-5073-717X
                Article
                ijms-20-03979
                10.3390/ijms20163979
                6720959
                31443326
                9b121396-9f57-4980-b275-79d3cacaf475
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 19 July 2019
                : 14 August 2019
                Categories
                Review

                Molecular biology
                alzheimer’s disease,mirna,in vivo experimental models
                Molecular biology
                alzheimer’s disease, mirna, in vivo experimental models

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