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

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.

Molecular and Cellular Mechanisms of Epilepsy

“…Two excellent reviews by Allan Kalueff's group provide translational insights into epilepsy from zebrafish models [10,11]. One review discusses recent advances and current challenges in the development of experimental models of mTOR-dependent epilepsy and other related mTORopathies [10].…”

“…Two excellent reviews by Allan Kalueff's group provide translational insights into epilepsy from zebrafish models [10,11]. One review discusses recent advances and current challenges in the development of experimental models of mTOR-dependent epilepsy and other related mTORopathies [10]. The other review focuses on current perspectives and challenges in the development of genetic, pharmacological and other experimental models of major CNS channelopathies based on zebrafish [11].…”