Targeting MicroRNAs in Prevention and Treatment of Neurodegenerative Disorders

Gupta, Smriti; Verma, Savita; Mantri, Shrikant; Berman, Nancy E.J.; Sandhir, Rajat

doi:10.1002/ddr.21277

Cited by 26 publications

(25 citation statements)

References 136 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Concordance between these two works suggests a potential role of miRNAs as therapeutic targets to regulate dysregulated mRNAs expression. Indeed, some studies had previously examined the involvement of a miRNA network in neurodegenerative diseases (Hebert and De Strooper, 2009; Lau et al, 2013; Ubhi et al, 2014) and demonstrated the possibility to target miRNAs to treat neurodegenerative disorders (Gupta et al, 2015; Weinberg and Wood, 2009). …”

Section: Discussionmentioning

confidence: 99%

MicroRNA screening identifies a link between NOVA1 expression and low level of IKAP/ELP1 in Familial dysautonomia

Hervé

Ibrahim

2016

Disease Models &Amp; Mechanisms

View full text Add to dashboard Cite

Familial dysautonomia (FD) is a rare neurodegenerative disease caused by a mutation in intron 20 of the IKBKAP gene (c.2204+6T>C), leading to tissue-specific skipping of exon 20 and a decrease in the synthesis of the encoded protein IKAP (also known as ELP1). Small non-coding RNAs known as microRNAs (miRNAs) are important post-transcriptional regulators of gene expression and play an essential role in the nervous system development and function. To better understand the neuronal specificity of IKAP loss, we examined expression of miRNAs in human olfactory ecto-mesenchymal stem cells (hOE-MSCs) from five control individuals and five FD patients. We profiled the expression of 373 miRNAs using microfluidics and reverse transcription coupled to quantitative PCR (RT-qPCR) on two biological replicate series of hOE-MSC cultures from healthy controls and FD patients. This led to the total identification of 26 dysregulated miRNAs in FD, validating the existence of a miRNA signature in FD. We then selected the nine most discriminant miRNAs for further analysis. The signaling pathways affected by these dysregulated miRNAs were largely within the nervous system. In addition, many targets of these dysregulated miRNAs had been previously demonstrated to be affected in FD models. Moreover, we found that four of our nine candidate miRNAs target the neuron-specific splicing factor NOVA1. We demonstrated that overexpression of miR-203a-3p leads to a decrease of NOVA1, counter-balanced by an increase of IKAP, supporting a potential interaction between NOVA1 and IKAP. Taken together, these results reinforce the choice of miRNAs as potential therapeutic targets and suggest that NOVA1 could be a regulator of FD pathophysiology.

show abstract

Section: Discussionmentioning

confidence: 99%

MicroRNA screening identifies a link between NOVA1 expression and low level of IKAP/ELP1 in Familial dysautonomia

Hervé

Ibrahim

2016

Disease Models &Amp; Mechanisms

View full text Add to dashboard Cite

show abstract

“…They tend to repress genes’ expression level through binding to specific sequences mostly located in the 3'‐untranslated region (3'UTR) of mRNAs, culminating in mRNA degradation or deadenylation and translation inhibition . miRNAs have an enormous modulatory potential considering that each single miRNA can govern expression of hundreds of different transcripts and that's why whole phenotype of a disease can be feasibly affected by regulating a single miRNA molecule . Mounting evidence has emerged showing the association between miRNA network and pathogenesis of neurodegenerative disorders including PD .…”

Section: Introductionmentioning

confidence: 99%

“…Mounting evidence has emerged showing the association between miRNA network and pathogenesis of neurodegenerative disorders including PD . Furthermore, altered level of several miRNAs has been reported in disparate PD models and human brains of patients suffering from PD . While there is substantial literature confirming miRNAs’ implication in PD development, only a few studies have attempted to identify deregulated miRNAs …”

Section: Introductionmentioning

confidence: 99%

Modified level of miR‐376a is associated with Parkinson's disease

Baghi

Delavar

Yadegari

et al. 2020

J Cellular Molecular Medi

View full text Add to dashboard Cite

Parkinson's disease (PD) is a frequent progressive neurodegenerative disorder. Impaired mitochondrial function is a major feature of sporadic PD. Some susceptibility or causative genes detected in PD are strongly associated with mitochondrial dysfunction including PGC1α, TFAM and GSK3β. microRNAs (miRNAs) are non‐coding RNAs whose altered levels are proven in disparate PD models and human brains. Therefore, the aim of this study was to detect modulations of miRs upstream of PGC1α, TFAM and GSK3β in association with PD onset and progress. In this study, a total of 33 PD subjects and 25 healthy volunteers were recruited. Candidate miRNA (miR‐376a) was selected through target prediction tools and literature survey. Chronic and acute in vitro PD models were created by MPP+‐intoxicated SHSY5Y cells. The levels of miR‐376a and aforementioned genes were assessed by RT‐qPCR. The expression of target genes was decreased in chronic model while there were dramatically up‐regulated levels of those genes in acute model of PD. miR‐376a was strongly altered in both acute and chronic PD models as well as PBMCs of PD patients. Our results also showed overexpression of PGC1α, and TFAM in PBMCs is inversely correlated with down‐regulation of miR‐376a, suggesting that miR‐376a possibly has an impact on PD pathogenesis through regulation of these genes which are involved in mitochondrial function. miR‐376a expression in PD‐derived PBMCs was also correlated with disease severity and may serve as a potential biomarker for PD diagnosis. This is the first study showing altered levels of miR‐376a in PD models and PBMCs, suggesting the probable role of this miRNA in PD pathogenesis. The present study also proposed TFAM and PGC1α as target genes of miR‐376a for the first time, through which it possibly can exert its impact on PD pathogenesis.

show abstract

“…Dysregulation of miRNA in the pathophysiology of polyQ disorders miRNA dysregulation is emerging as a critical factor contributing to neurodegeneration [105][106][107][108][109][110][111][112]. Major alterations in brain mRNA levels have been observed in various neurodegenerative disorders, and as mentioned above, altered neuronal transcriptional activity is a persistent feature of most polyQ disorders.…”

Section: Histone Modifications and Chromatin Remodeling In Polyq Disordersmentioning

confidence: 99%

Welcome to the 10th volume of Epigenomics

Martin

2017

Epigenomics

View full text Add to dashboard Cite

Targeting MicroRNAs in Prevention and Treatment of Neurodegenerative Disorders

Cited by 26 publications

References 136 publications

MicroRNA screening identifies a link between NOVA1 expression and low level of IKAP/ELP1 in Familial dysautonomia

MicroRNA screening identifies a link between NOVA1 expression and low level of IKAP/ELP1 in Familial dysautonomia

Modified level of miR‐376a is associated with Parkinson's disease

Welcome to the 10th volume of Epigenomics

Contact Info

Product

Resources

About