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MicroRNAs as targets in the epilepsies: hits, misses and complexes
MicroRNAs are small noncoding RNAs that provide a critical layer of gene expression control. Individual microRNAs variably exert effects across networks of genes via sequence-specific binding to mRNAs, fine-tuning protein levels. This helps coordinate the timing and specification of cell fate transitions during brain development and maintains neural circuit function and plasticity by activity-dependent (re)shaping of synapses and the levels of neurotransmitter components. MicroRNA levels have been found to be altered in tissue from the epileptogenic zone resected from adults with drug-resistant focal epilepsy and this has driven efforts to explore their therapeutic potential, in particular using antisense oligonucleotide (ASOs) inhibitors termed antimirs. Here, we review the molecular mechanisms by which microRNAs control brain excitability and the latest progress towards a microRNA-based treatment for temporal lobe epilepsy. We also look at whether microRNA-based approaches could be used to treat genetic epilepsies, correcting individual genes or dysregulated pathways. Finally, we look at how cells have evolved to maximise the efficiency of the microRNA system via RNA editing, where single base changes is capable of altering the repertoire of genes under the control of a single microRNA. The findings improve our understanding of the molecular landscape of the epileptic brain and may lead to new therapies.
Neuronal RNA signatures: Regulation and Function
Neurons are uniquely complex cells characterized by the expression of RNA sequences that are found in no other cell type: neuron-specific mRNA splice isoforms, circular RNAs, microRNAs, and ultra-long 3’UTRs. Although relatively little is known about how these neuronal RNA signatures control neuronal development and function, the importance of RNA-directed regulation in the brain is exemplified by its implication in neurological diseases. Our goal is to gain mechanistic and functional insight of the neuron-specific RNA landscape that drives neural function in health and disease.
EPILEPTOGENIC INSULTS IMPACT THE EPITRANSCRIPTOMIC (N6-METHYLADENOSINE/M6A) SIGNATURE OF MATURE MICRORNAS AND REGULATES THEIR ROLE IN EPILEPSY DEVELOPMENT
FENS Forum 2026
EV-ASSOCIATED MICRORNAS AS POTENTIAL BIOMARKERS FOR 22Q11.2DS AND ASSOCIATED DISORDERS IN AN IPSC MODEL; COMPARISON OF CENTRAL AND PERIPHERAL BIOMARKERS
FENS Forum 2026
DEREGULATION OF CIRCULATING MICRORNAS AFTER REPETITIVE HEAD IMPACTS IN ELITE FEMALE FOOTBALL PLAYERS
FENS Forum 2026
ADAM10-TARGETING MICRORNAS IN SERUM AS PERIPHERAL BIOMARKERS LINKING ALZHEIMER’S DISEASE AND TYPE 2 DIABETES
FENS Forum 2026
WIDESPREAD CNS TARGETING BY ALLELE-SPECIFIC BICISTRONIC MICRORNAS IMPROVES MOTOR AND MOLECULAR OUTCOMES IN SPINOCEREBELLAR ATAXIA TYPE 3
FENS Forum 2026
TARGETING AGE-DYSREGULATED MICRORNAS TO RESCUE OLIGODENDROCYTE PROGENITOR CELLS DURING AGING
FENS Forum 2026
Altered expression of peripheral microRNAs and pathway signaling after mild traumatic brain injury
Differential roles for dysregulated microRNAs after a peripheral nerve injury in neuropathic pain or nerve regeneration
FENS Forum 2024
microRNAs regulating CaMKIIα/SIRT1 signaling pathway are associated with cognitive ability and academic performance in adolescents
FENS Forum 2024
Circulating microRNAs and isomiRs as biomarkers for the initial insult and epileptogenesis in four experimental epilepsy models – The EPITARGET study
FENS Forum 2024
Cannabidiol modulates alterations in PFC microRNAs in a rat model of depression
Cell-type-specific profiling of microRNAs during epileptogenesis: Insights into neurons and microglia microRNA profiles in normal brain function and disease
The emerging role of microRNAs in experimental and clinical multiple sclerosis: implications for inflammation-driven synaptic dysfunctions and disease course
Functional analysis of microRNAs in auditory brainstem of mice
Circulating microRNAs as biomarkers for Alzheimer’s disease
FENS Forum 2024
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