Topic: mTORopathies

Epilepsy is a common comorbidity of mTORopathies such a Tuberous Sclerosis Complex (TSC) and mTOR hyperactivity-associated Fragile X Syndrome (FXS), both characterized by severe cognitive dysfunctions. On the other hand, medial Temporal Lobe Epilepsy (mTLE) is associated with mTOR hyperactivity within the hippocampal formation and cognitive deficits, particularly pertaining to pattern separation and episodic memory. The hippocampal dentate gyrus (DG) subregion is crucial for gating the flow and separating the patterns of cortical information inputs, transmitting them via DG granule cell mossy

Mechanistic target of rapamycin (mTOR) is a serine/threonine kinase that regulates fundamental cellular processes including growth control, autophagy and metabolism. mTOR constitutes the catalytic subunit of two signalling complexes: mTOR complex 1 (mTORC1) and 2 (mTORC2). Manipulating mTORC1 signalling in animal models has shown that this pathway has key roles in neurogenesis, and mTORC1 hyperactivation during neurodevelopment causes a group of disorders known as mTORopathies. mTORopathies typically involve brain malformations and neurological manifestations like epilepsy. One example is tube

The kinase Mammalian Target of Rapamycin (mTOR) plays a pivotal role in cellular metabolism and growth across diverse cell types. In neurons, mTOR assumes critical importance for both neuronal development and plasticity. Dysregulation of mTOR has been implicated in mTORopathies, including Tuberous Sclerosis Complex (TSC) and associated brain disorders like epilepsy. Despite its predominant cytoplasmic localization, several studies have reported the presence of mTOR in the nucleus. Through mass spectrometry analysis, we identified Brg1, the catalytic subunit of the BAF chromatin remodelling com

The mTOR pathway is a pivotal cellular signaling pathway that impacts neuronal differentiation and function. Genetic disruptions leading to hyperactivation of the mTOR pathway, termed mTORopathies, represent rare genetic and systemic disorders that are associated with altered brain development and epilepsy. However, the precise mechanisms by which disrupted mTOR signaling affects neuronal network development and signaling remain poorly understood. Human induced pluripotent stem cells (iPSCs) and CRISPR/Cas9 genome editing, allowed the generation of a panel of isogenic iPSC lines carrying mutat