Environmental Influencers, MicroRNA, and Multiple Sclerosis

Mohammed, Eiman Ma

doi:10.1177/1179573519894955

Cited by 33 publications

(22 citation statements)

References 269 publications

(754 reference statements)

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“…Small noncoding microRNAs (miRNAs or miR) are an important class of molecules critically involved in modulating gene expression and are considered sensitive biomarkers and potential therapeutic targets for many diseases 8,9 . Notably, altered expression of various miRNAs (including, miR‐155 and miR‐21) have been detected in the peripheral blood, CSF and brain tissue of MS patients and in one of the most widely used animal model of MS, experimental autoimmune encephalomyelitis (EAE) 10,11 . It has been shown that different therapeutic approaches may modulate the expression and activity of specific miRNA and particularly of miR‐142‐3p 12–14 .…”

Section: Introductionmentioning

confidence: 99%

MiR‐142‐3p regulates synaptopathy‐driven disease progression in multiple sclerosis

Vito

Musella

Fresegna

et al. 2021

Neuropathology Appl Neurobio

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Aim We recently proposed miR‐142‐3p as a molecular player in inflammatory synaptopathy, a new pathogenic hallmark of multiple sclerosis (MS) and of its mouse model experimental autoimmune encephalomyelitis (EAE), that leads to neuronal loss independently of demyelination. MiR‐142‐3p seems to be unique among potential biomarker candidates in MS, since it is an inflammatory miRNA playing a dual role in the immune and central nervous systems. Here, we aimed to verify the impact of miR‐142‐3p circulating in the cerebrospinal fluid (CSF) of MS patients on clinical parameters, neuronal excitability and its potential interaction with disease modifying therapies (DMTs). Methods and Results In a cohort of 151 MS patients, we found positive correlations between CSF miR‐142‐3p levels and clinical progression, IL‐1β signalling as well as synaptic excitability measured by transcranial magnetic stimulation. Furthermore, therapy response of patients with ‘low miR‐142‐3p’ to dimethyl fumarate (DMF), an established disease‐modifying treatment (DMT), was superior to that of patients with ‘high miR‐142‐3p’ levels. Accordingly, the EAE clinical course of heterozygous miR‐142 mice was ameliorated by peripheral DMF treatment with a greater impact relative to their wild type littermates. In addition, a central protective effect of this drug was observed following intracerebroventricular and ex vivo acute treatments of EAE wild type mice, showing a rescue of miR‐142‐3p‐dependent glutamatergic alterations. By means of electrophysiology, molecular and biochemical analysis, we suggest miR‐142‐3p as a molecular target of DMF. Conclusion MiR‐142‐3p is a novel and potential negative prognostic CSF marker of MS and a promising tool for identifying personalised therapies.

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Section: Introductionmentioning

confidence: 99%

MiR‐142‐3p regulates synaptopathy‐driven disease progression in multiple sclerosis

Vito

Musella

Fresegna

et al. 2021

Neuropathology Appl Neurobio

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“…to show that the empirical distribution of the overlaps does not match with the expected hypergeometric distribution. First, we selected miRNAs dysregulated in multiple sclerosis, from Table 5 in [15] (see supporting information) and gene ontology (GO) annotations from Ensembl [23] version 100. Also we retrieved disease-to-gene associations from DisGeNET v7 [18], as well as pathway data from KEGG [11].…”

Section: Methodsmentioning

confidence: 99%

Bias in miRNA enrichment analysis related to gene functional annotations

Zagganas

Γεωργακίλας

Vergoulis

et al. 2021

Preprint

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Motivation: miRNA functional enrichment is a type of analysis that is used to predict which biological functions may be affected by a group of miRNAs or validate whether a list of dysreg- ulated miRNAs are linked to a diseased state. The standard method for functional enrichment analysis uses the hypergeometric distribution to produce p-values, depicting the strength of the association between a group of miRNAs and a biological function. However, in 2015, it was shown that this approach suffers from a bias related to miRNA targets produced by target prediction algorithms and a new randomization test was proposed. Results: In this paper, we demonstrate the existence of another underlying bias which affects gene annotation data sets; additionally, we show that the statistical measure used for the estab- lished randomization test is not sensitive enough to account for it. For this reason, we propose the use of an alternative statistical measure, the "two-sided overlap", and we show that it is able to alleviate the aforementioned issue. Finally, we develop BUFET2, a miRNA enrichment analysis tool that leverages this measure (along with the old one); it is based on BUFET, a fast and scalable implementation of the established randomization test. Availability and Implementation: BUFET2 is written in C++ and is packaged with a Python wrapper script that facilitates experiment execution. Moreover, BUFET2 also comes pre-packaged in a Linux Docker image published on Docker Hub, thus eliminating the need for code compilation. Finally, BUFET2 is also publicly available to execute through a REST API. All datasets used in the experiments throught this paper are openly accessible on Zenodo (https://doi.org/10.5281/zenodo.5175819).

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“…miR-17, miR-21, miR-320, and miR-150 exhibited different patterns across the compartments in MS patients with predominant upregulation in the CNS lesions and downregulation in the immune tissue [55,58,59]. Interestingly, It has been reported that miR-21 exhibit both pro-and anti-inflammatory functions.…”

Section: Mirna Dysregulation Multiple Sclerosismentioning

confidence: 99%

MicroRNAs in central nervous system disorders: current advances in pathogenesis and treatment

Hussein

Magdy

2021

Egypt J Neurol Psychiatry Neurosurg

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MicroRNAs (miRNAs) are a class of short, non-coding, regulatory RNA molecules that function as post transcriptional regulators of gene expression. Altered expression of multiple miRNAs was found to be extensively involved in the pathogenesis of different neurological disorders including Alzheimer’s disease, Parkinson’s disease, stroke, epilepsy, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington’s disease. miRNAs are implicated in the pathogenesis of excitotoxicity, apoptosis, oxidative stress, inflammation, neurogenesis, angiogenesis, and blood–brain barrier protection. Consequently, miRNAs can serve as biomarkers for different neurological disorders. In recent years, advances in the miRNA field led to identification of potentially novel prospects in the development of new therapies for incurable CNS disorders. MiRNA-based therapeutics include miRNA mimics and inhibitors that can decrease or increase the expression of target genes. Better understanding of the mechanisms by which miRNAs are implicated in the pathogenesis of neurological disorders may provide novel targets to researchers for innovative therapeutic strategies.

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Environmental Influencers, MicroRNA, and Multiple Sclerosis

Cited by 33 publications

References 269 publications

MiR‐142‐3p regulates synaptopathy‐driven disease progression in multiple sclerosis

MiR‐142‐3p regulates synaptopathy‐driven disease progression in multiple sclerosis

Bias in miRNA enrichment analysis related to gene functional annotations

MicroRNAs in central nervous system disorders: current advances in pathogenesis and treatment

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