Epigenetic and post-transcriptional control of epileptogenesis by NEAT1: From molecular pathways to biomarker...

Epilepsy, a chronic neurological condition that is defined by episodes of spontaneous recurrent seizures initiated by abnormal excessive neuronal synchronisation and cortical hyperexcitability. Despite the progress in diagnostic procedures and in the creation of antiepileptic drugs, about one-third of the patients persist in experiencing drug-recalcitrant epilepsy, thus enhancing the necessity to establish new therapeutic as well as diagnostic signals. The recent studies on the epigenetic and post-transcriptional controllers have more and more become increasingly interested in the non-coding RNAs due to their emerging functions in neural signaling and disease pathology. In this regard, special attention has been given to the long non-coding RNA Nuclear Enriched Abundant Transcript 1 (NEAT1) because its regulatory functions in neuroinflammation, apoptosis, oxidative stress, neuronal excitability and synaptic plasticity have been heavily involved in epileptogenesis. NEAT1 exists in two alternatively processed variants, NEAT1_1 and NEAT1_2, and the relative abundance of these variants is critical for paraspeckle assembly and nuclear RNA retention dynamics. Regular reports of its dysregulation have become apparent in experimental models of seizure and also in clinical samples, especially drug-resistant epilepsy. NEAT1 has a mechanistic role in inflammatory cascades and participates in maladaptive re-shaping of mitochondrial and synaptic activities. Reduced NEAT1 expression mitigates seizure severity, neuroinflammation, and oxidative damage, as preclinical knockdown experiments reveal, thereby promoting the relevance of the therapy to the wider clinical context. Further, there is clinical evidence that NEAT1 could be a non-invasive biomarker for prediction and diagnosis.