Abstract
Epilepsy represents one of the most common neurological disorders characterized by abnormal electrical activity in the central nervous system (CNS). Recurrent seizures are the cardinal clinical manifestation. Although it has been reported that the underlying pathological processes include inflammation, changes in synaptic strength, apoptosis, and ion channels dysfunction, currently the pathogenesis of epilepsy is not yet completely understood. Long non-coding RNAs (lncRNAs), a class of long transcripts without protein-coding capacity, have emerged as regulatory molecules that are involved in a wide variety of biological processes. A growing number of studies reported that lncRNAs participate in the regulation of pathological processes of epilepsy and they are dysregulated during epileptogenesis. Moreover, an aberrant expression of lncRNAs linked to epilepsy has been observed both in patients and in animal models. In this review, we summarize latest advances concerning the mechanisms of action and the involvement of the most dysregulated lncRNAs in epilepsy. However, the functional roles of lncRNAs in the disease pathogenesis are still to be explored and we are only at the beginning. Additional studies are needed for the complete understanding of the underlying mechanisms and they would result in the use of lncRNAs as diagnostic biomarkers and novel therapeutic targets.
Highlights
Recent advances in genome-wide transcriptome sequencing technologies, along with the availability of suitable bioinformatics tools, have revealed that protein-coding genes only represent about 2% of the human transcripts, whereas the rest of the genome encodes for mainly non-coding RNAs
A potential therapeutic intervention, based on the reduction of the UBE3A antisense transcript (UBE3A-ATS) Long non-coding RNAs (lncRNAs), has been successful proposed in patients affected by Angelman syndrome, a genetic disorder that is caused by maternal deficiency of the imprinted gene UBE3A and characterized by intellectual disability, severe speech impairment, developmental delay, seizures, and ataxia [74]
The experience gained in these clinical fields may lead to their applications in epilepsy: promising results have already been achieved modulating SCN1A expression in vivo by specific ASO blocking SCN1ANAT lncRNA [47]
Summary
Recent advances in genome-wide transcriptome sequencing technologies, along with the availability of suitable bioinformatics tools, have revealed that protein-coding genes only represent about 2% of the human transcripts, whereas the rest of the genome encodes for mainly non-coding RNAs (ncRNAs). Concerning cellular localization, the lncRNA mature molecules are found within the nucleus, the cytosol, and even in mitochondria [5,6] According to their position in the genome and orientation in respect to the adjacent protein-coding genes, lncRNAs can be subclassified into major groups: sense, antisense, intronic, intergenic, and bidirectional [7]. Emerging evidences suggested an important role of lncRNAs in molecular mechanisms that are already associated with epilepsy, mainly regarding brain excitability and seizure thresholds They are known to regulate several processes: e.g., gliosis, neuroinflammation, neuronal death, synaptic plasticity, changes to ion channels and transmitter receptors, and network-level remodeling [22]
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