# Modeling the microRNA regulation of TGF-β/SMAD signaling pathways for seizure control in temporal lobe epilepsy

## TL;DR

This study explores how microRNA regulation of TGF-β/SMAD signaling could help control seizures in temporal lobe epilepsy.

## Contribution

The novelty lies in modeling microRNA regulation of TGF-β/SMAD signaling to identify seizure suppression strategies.

## Key findings

- Inhibition of specific microRNAs using antagomirs can shift cellular states from seizure to anti-seizure.
- Promising antagomir dosages and strategies for seizure suppression were identified.
- The regulatory effects of miR-21a-5p, miR-142a-5p, and miR-10a-5p were analyzed in epilepsy models.

## Abstract

Temporal lobe epilepsy (TLE) is the most prevalent type of focal epilepsy. Recent developments in sequencing, proteomics and network analysis tools provide new avenues for investigating potential molecular therapeutic targets. Both the TGF-β/SMAD signaling pathways and subsets of microRNAs (including miR-21a-5p, miR-142a-5p, and miR-10a-5p) have been shown to be altered in several preclinical models of epilepsy and were mathematically modeled in this study. Using prior systems-based findings, a changeover between ‘seizure’ and ‘anti-seizure’ cellular states has been identified upon inhibition of microRNA activity achieved by the injection of antagomirs. Methods for seizure suppression were explored under various antagomir dosages as well as the regulatory effect of each microRNA in order to ascertain intracellular responses. Promising antagomir administration strategies were then identified, which may offer new avenues for seizure suppression.