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<p>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-<i>β</i>/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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月15日

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  • Kurt J. A. Pumares,
  • Daniel P. Martins,
  • Aiman Khalil,
  • Jochen H. M. Prehn,
  • Deirdre Kilbane

摘要

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.