Fig. 2

The role of mTOR pathway in epileptogenesis. Dysmorphic neurons and balloon cells, which lack dendrites or axons, undergo alterations in neurotransmitter receptor subunit expression and uptake site distribution in conditions like TSC, FCD, and hemimegalencephaly (HME). Notably, changes are prominent in GluR, NMDAR, and mGluR subtypes. The direct causation of these alterations—whether they arise from heightened mTOR signaling, tissue cytoarchitecture changes, or adaptations stemming from recurrent seizures—remains uncertain. The accompanying diagram illustrates various locations where dysregulation of mTORC1 (influenced by both phosphoactivation and phosphoinhibition effects) is implicated in human neurological disorders collectively referred to as “mTORopathies,” which encompass epilepsy. Components such as PTEN, STRADA, TSC1/TSC2, and S6K1 might play roles in this context. Experimental animal models involving these proteins also exhibit compromised seizure susceptibility and/or deficits in social and behavioral functions. Rapamycin and other mTOR inhibitors emerge as primary potential therapeutic agents for modulating mTORC1 signaling. These interventions hold promise for regulating the mTOR pathway, offering prospects for addressing the underlying mechanisms of mTOR-related neurological disorders, including epilepsy [21, 25]. Adapted from Crino [21]