Developing Novel Experimental Models of m-TORopathic Epilepsy and Related Neuropathologies: Translational Insights from Zebrafish

Int J Mol Sci. 2023 Jan 12;24(2):1530. doi: 10.3390/ijms24021530.

Abstract

The mammalian target of rapamycin (mTOR) is an important molecular regulator of cell growth and proliferation. Brain mTOR activity plays a crucial role in synaptic plasticity, cell development, migration and proliferation, as well as memory storage, protein synthesis, autophagy, ion channel expression and axonal regeneration. Aberrant mTOR signaling causes a diverse group of neurological disorders, termed 'mTORopathies'. Typically arising from mutations within the mTOR signaling pathway, these disorders are characterized by cortical malformations and other neuromorphological abnormalities that usually co-occur with severe, often treatment-resistant, epilepsy. Here, we discuss recent advances and current challenges in developing experimental models of mTOR-dependent epilepsy and other related mTORopathies, including using zebrafish models for studying these disorders, as well as outline future directions of research in this field.

Keywords: animal model; mTOR; mTORopathy; signaling pathway; zebrafish.

Publication types

  • Review

MeSH terms

  • Animals
  • Disease Models, Animal
  • Epilepsy* / genetics
  • Epilepsy* / metabolism
  • Mammals / metabolism
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism
  • Zebrafish* / metabolism

Substances

  • TOR Serine-Threonine Kinases