Genome-wide microRNA profiling of plasma from three different animal models identifies biomarkers of temporal lobe epilepsy

Brennan, Gary P.; Bauer, Sebastian; Engel, Tobías; Jiménez-Mateos, Eva M.; Gallo, Federico Del; Hill, Thomas; Connolly, Niamh M. C.; Costard, Lara S.; Neubert, Valentin; Salvetti, Beatrice; Sanz-Rodríguez, Amaya; Heiland, Mona; Mamad, Omar; Brindley, Elizabeth; Norwood, Braxton A.; Batool, Aasia; Raoof, Rana; El‐Naggar, Hany; Reschke, Cristina R.; Delanty, Norman; Prehn, Jochen H M; Fabene, Paolo F.; Mooney, Catherine; Rosenow, Felix; Henshall, David C.

doi:10.1016/j.nbd.2020.105048

Cited by 36 publications

(20 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…So far, new biomarkers for the diagnosis of epilepsy are still being evaluated. The expression changes of various miRNAs identified by expression profiling of circulating miRNA have been confirmed in epilepsy patients (Antônio et al, 2019;Brennan et al, 2020). There is evidence that epilepsy is associated with the expression changes observed in the circulating miRNAs.…”

Section: Mirnas As Biomarkers Of Epilepsymentioning

confidence: 81%

MicroRNA Dysregulation in Epilepsy: From Pathogenetic Involvement to Diagnostic Biomarker and Therapeutic Agent Development

Wang

Zhao

2021

Front. Mol. Neurosci.

View full text Add to dashboard Cite

Epilepsy is the result of a group of transient abnormalities in brain function caused by an abnormal, highly synchronized discharge of brain neurons. MicroRNA (miRNA) is a class of endogenous non-coding single-stranded RNA molecules that participate in a series of important biological processes. Recent studies demonstrated that miRNAs are involved in a variety of central nervous system diseases, including epilepsy. Although the exact mechanism underlying the role of miRNAs in epilepsy pathogenesis is still unclear, these miRNAs may be involved in the inflammatory response in the nervous system, neuronal necrosis and apoptosis, dendritic growth, synaptic remodeling, glial cell proliferation, epileptic circuit formation, impairment of neurotransmitter and receptor function, and other processes. Here, we discuss miRNA metabolism and the roles of miRNA in epilepsy pathogenesis and evaluate miRNA as a potential new biomarker for the diagnosis of epilepsy, which enhances our understanding of disease processes.

show abstract

Section: Mirnas As Biomarkers Of Epilepsymentioning

confidence: 81%

MicroRNA Dysregulation in Epilepsy: From Pathogenetic Involvement to Diagnostic Biomarker and Therapeutic Agent Development

Wang

Zhao

2021

Front. Mol. Neurosci.

View full text Add to dashboard Cite

show abstract

“…There is accumulating evidence that the miRNA landscape is dysregulated in epilepsy [29,[40][41][42][43] and other brain diseases [44][45][46][47][48], raising prospects for treating disease by over-or underexpressing key miRNAs. Key experimental tools for miRNA targeting are summarised in Figure 1.…”

Section: 'Drugging' Mirnasmentioning

confidence: 99%

Opportunities and challenges for microRNA-targeting therapeutics for epilepsy

Morris

O’Brien²,

Henshall

2021

Trends in Pharmacological Sciences

Self Cite

View full text Add to dashboard Cite

Epilepsy is a common and serious neurological disorder characterised by recurrent spontaneous seizures. Frontline pharmacotherapy includes small-molecule antiseizure drugs that typically target ion channels and neurotransmitter systems, but these fail in 30% of patients and do not prevent either the development or progression of epilepsy. An emerging therapeutic target is microRNA (miRNA), small noncoding RNAs that negatively regulate sets of proteins. Their multitargeting action offers unique advantages for certain forms of epilepsy with complex underlying pathophysiology, such as temporal lobe epilepsy (TLE). miRNA can be inhibited by designed antisense oligonucleotides (ASOs; e.g., antimiRs). Here, we outline the prospects for miRNA-based therapies. We review design considerations for nucleic acid-based approaches and the challenges and next steps in developing therapeutic miRNA-targeting molecules for epilepsy.Current versus future drugs for epilepsy: the need for change Epilepsy (see Glossary) is a common, often life-long brain disease characterised by recurrent, spontaneous seizures that are the result of hypersynchronous discharges of neurons [1]. There are more than 20 different small-molecule drugs in clinical use that reduce or prevent seizures in people with epilepsy. This is a remarkable achievement, certainly relative to the lack of treatments for many neurological disorders, and is owed to a solid mechanistic understanding of how seizures arise through imbalances between excitation and inhibition and the availability of good disease models that identify molecules with antiexcitability properties [2]. However, antiseizure drugs likely do not substantially alter the underlying pathophysiology of epilepsy, and one-third of patients are refractory to current treatments. Addressing this treatment gap is a major priority [1,3], and, increasingly, researchers are looking at substantially different targets.Acquired forms of epilepsy, such as TLE, have a limited genetic basis and probably arise from an earlier brain insult that leads to select cell loss, gliosis, neuroinflammation, and vascular and microscopic as well as macroscopic reorganisation of brain networks [4,5]. Because of this, single targets, such as ion channels, may be unsuitable or insufficient to overcome drug resistance, achieve disease modification, or prevent epileptogenesis [6] (Box 1). Novel approaches that can modify multiple targets may be necessary. Additionally, suitable target(s) may not reside on the outside of neurons but instead be intracellular. Both challenges could be solved by using RNAbased medicines such as ASOs, which offer virtually unlimited potential to target any gene, and small noncoding RNAs called microRNAs (miRNAs), which are 'multi-pathway' regulatory molecules (for a recent review on the general topic of RNA medicines, the reader is referred elsewhere [7]).The first miRNA medicine reached human trials in 2013 [8], and several others are in clinical testing. The versatility of ASO-based medicines was elegantly dem...

show abstract

“…48 However, according to the latest results, miRNAs seem specific for epilepsy irrespective of seizure and brain activity. 42 Moreover, some miRNAs are enriched in the brain, with several miRNAs being almost exclusive to brain tissue. 42,49 As Organista-Juárez et al 24 point out, more than 1000 miRNAs are differentially expressed in different brain regions of human and experimental epilepsy.…”

Section: Biomarker Potential In Epilepsymentioning

confidence: 99%

“…33,[35][36][37][38] Stemming from their role as fine-tuners of gene expression, miRNA expression levels mirror the cell's processes. Therefore, we can observe temporospatial specificity of miRNA expression, creating a pattern particular for each organ, 39 tissue, 40,41 or cell type 42,43 in each moment, 44 not only in respective locations but also in body fluids, 45 if functionally associated with the process of interest. A unique opportunity arises to facilitate miRNAs as biomarkers of ongoing pathology and create novel, more precise clinical guidelines for assessing diagnosis, prognosis, and overall clinical outcome of patients with about any complex disease.…”

Section: Biomarker Potential In Epilepsymentioning

confidence: 99%

MicroRNAs in the development of resistance to antiseizure drugs and their potential as biomarkers in pharmacoresistant epilepsy

et al. 2021

View full text Add to dashboard Cite

Epilepsy is a group of heterogeneous syndromes affecting more than 50 million people worldwide. Although many new antiseizure drugs (ASDs) have been developed in the past decade, approximately 30%-40% of patients remain pharmacoresistant (drug-resistant epilepsy [DRE], pharmacoresistant epilepsy, intractable epilepsy, refractory epilepsy). Furthermore, up to now, no effective treatment exists to prevent the development of epilepsy despite

show abstract

Genome-wide microRNA profiling of plasma from three different animal models identifies biomarkers of temporal lobe epilepsy

Cited by 36 publications

References 74 publications

MicroRNA Dysregulation in Epilepsy: From Pathogenetic Involvement to Diagnostic Biomarker and Therapeutic Agent Development

MicroRNA Dysregulation in Epilepsy: From Pathogenetic Involvement to Diagnostic Biomarker and Therapeutic Agent Development

Opportunities and challenges for microRNA-targeting therapeutics for epilepsy

MicroRNAs in the development of resistance to antiseizure drugs and their potential as biomarkers in pharmacoresistant epilepsy

Contact Info

Product

Resources

About