Neuroprotection of microRNA in neurological disorders (Review)

Wang, Chunmei; Ji, Bingyuan; Cheng, Baohua; Chen, Jing; Bai, Bo

doi:10.3892/br.2014.297

Cited by 53 publications

(39 citation statements)

References 72 publications

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“…The role of miR223 in the brain has been investigated. miR-223 is expressed in the brain, regulates the differentiation of immature neurons[29], and exerts a neuroprotective role[30]. It was also reported that miR-223 is upregulated in PD and MSA compared to the controls [31].…”

Section: Discussionmentioning

confidence: 99%

Genetic analysis of α‐synuclein 3′ untranslated region and its corresponding microRNAs in relation to Parkinson's disease compared to dementia with Lewy bodies

Tagliafierro

Glenn

Zamora

et al. 2017

Alzheimer's & Dementia

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INTRODUCTION The alpha-synuclein (SNCA) gene has been implicated in the etiology of Parkinson’s disease (PD) and Dementia with Lewy Bodies (DLB). METHODS A computational analysis of SNCA-3’UTR to identify potential microRNA binding-sites, and quantitative real-time-PCR to determine their expression in isogenic iPSC-derived dopaminergic and cholinergic neurons as a model of PD and DLB, respectively. Additionally, deep sequencing analysis of SNCA-3’UTR of autopsy confirmed cases of PD, DLB, and normal followed by genetic association analysis of the identified variants. RESULTS We identified four miRNA binding-sites, and observed a neuronal-type specific expression profile for each miRNA in the different isogenic iPSC-derived neurons, i.e. dopaminergic and cholinergic. Furthermore, we found that the short-structural variant rs777296100-polyT was moderately associated with DLB but not with PD. DISCUSSION We suggest that the regulation of SNCA expression through miRNAs is neuronal-type specific, and possibly plays a part in the phenotypic heterogeneity of synucleinopathies. Furthermore, genetic variability in the SNCA gene may contribute to synucleinopathies in a pathology-specific manner.

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Section: Discussionmentioning

confidence: 99%

Genetic analysis of α‐synuclein 3′ untranslated region and its corresponding microRNAs in relation to Parkinson's disease compared to dementia with Lewy bodies

Tagliafierro

Glenn

Zamora

et al. 2017

Alzheimer's & Dementia

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“…miRNAs are considered to play significant roles in many biologic processes, including cellular proliferation, differentiation, maturation, and apoptosis [4] . In addition, miRNAs have been implicated in the pathogenesis of common human diseases, such as cardiovascular [5] , neurologic [6] , and hematologic diseases, cancer [7] , and inflammatory and autoimmune diseases [8] . These research findings have led to new insights into IBD pathogenesis.…”

Section: Introductionmentioning

confidence: 99%

miRNAs as new molecular insights into inflammatory bowel disease: Crucial regulators in autoimmunity and inflammation

Zhang

2016

WJG

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Inflammatory bowel disease (IBD) is characterized by chronic relapsing inflammatory disorders of the gastrointestinal tract, and includes two major phenotypes: ulcerative colitis and Crohn's disease. The pathogenesis of IBD is not fully understood as of yet. It is believed that IBD results from complicated interactions between environmental factors, genetic predisposition, and immune disorders. miRNAs are a class of small non-coding RNAs that can regulate gene expression by targeting the 3′-untranslated region of specific mRNAs for degradation or translational inhibition. miRNAs are considered to play crucial regulatory roles in many biologic processes, such as immune cellular differentiation, proliferation, and apoptosis, and maintenance of immune homeostasis. Recently, aberrant expression of miRNAs was revealed to play an important role in autoimmune diseases, including IBD. In this review, we discuss the current understanding of how miRNAs regulate autoimmunity and inflammation by affecting the differentiation, maturation, and function of various immune cells. In particular, we focus on describing specific miRNA expression profiles in tissues and peripheral blood that may be associated with the pathogenesis of IBD. In addition, we summarize the opportunities for utilizing miRNAs as new biomarkers and as potential therapeutic targets in IBD.

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“…Furthermore, within 4 d following Dox administration, dTg-211 mice presented fourfold increases in the forebrain levels of miR-134 (Fig. 4F), known to be causally involved with the induction of convulsive seizures (7,10,11,47).…”

Section: Mir-211 Declinementioning

confidence: 99%

“…Also, miR-211 levels are elevated in epileptic human brain tissues (47), and epileptic events are arguably common in the AD brain (54). Therefore, the possibility of a miR-211 involvement in this condition should be explored.…”

Section: Mir-211 Excess Associates With Impaired Learning Strategy Inmentioning

confidence: 99%

Dynamic changes in murine forebrain miR-211 expression associate with cholinergic imbalances and epileptiform activity

Bekenstein

Mishra

Milikovsky

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Epilepsy is a common neurological disease, manifested in unprovoked recurrent seizures. Epileptogenesis may develop due to genetic or pharmacological origins or following injury, but it remains unclear how the unaffected brain escapes this susceptibility to seizures. Here, we report that dynamic changes in forebrain micro-RNA (miR)-211 in the mouse brain shift the threshold for spontaneous and pharmacologically induced seizures alongside changes in the cholinergic pathway genes, implicating this miR in the avoidance of seizures. We identified miR-211 as a putative attenuator of cholinergicmediated seizures by intersecting forebrain miR profiles that were Argonaute precipitated, synaptic vesicle target enriched, or differentially expressed under pilocarpine-induced seizures, and validated TGFBR2 and the nicotinic antiinflammatory acetylcholine receptor nAChRa7 as murine and human miR-211 targets, respectively. To explore the link between miR-211 and epilepsy, we engineered dTg-211 mice with doxycycline-suppressible forebrain overexpression of miR-211. These mice reacted to doxycycline exposure by spontaneous electrocorticography-documented nonconvulsive seizures, accompanied by forebrain accumulation of the convulsive seizures mediating miR-134. RNA sequencing demonstrated in doxycycline-treated dTg-211 cortices overrepresentation of synaptic activity, Ca 2+ transmembrane transport, TGFBR2 signaling, and cholinergic synapse pathways. Additionally, a cholinergic dysregulated mouse model overexpressing a miR refractory acetylcholinesterase-R splice variant showed a parallel propensity for convulsions, miR-211 decreases, and miR-134 elevation. Our findings demonstrate that in mice, dynamic miR-211 decreases induce hypersynchronization and nonconvulsive and convulsive seizures, accompanied by expression changes in cholinergic and TGFBR2 pathways as well as in miR-134. Realizing the importance of miR-211 dynamics opens new venues for translational diagnosis of and interference with epilepsy.

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Neuroprotection of microRNA in neurological disorders (Review)

Cited by 53 publications

References 72 publications

Genetic analysis of α‐synuclein 3′ untranslated region and its corresponding microRNAs in relation to Parkinson's disease compared to dementia with Lewy bodies

Genetic analysis of α‐synuclein 3′ untranslated region and its corresponding microRNAs in relation to Parkinson's disease compared to dementia with Lewy bodies

miRNAs as new molecular insights into inflammatory bowel disease: Crucial regulators in autoimmunity and inflammation

Dynamic changes in murine forebrain miR-211 expression associate with cholinergic imbalances and epileptiform activity

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