Topic: Tsc2

Several anxiety-related neuropsychiatric disorders are associated with amygdala dysfunction during early periods of postnatal development, and adolescence is a particularly vulnerable emotional period. Among the cellular mechanisms involved in changes in the activity of individual neurons and their synaptic connections, the mTOR signaling pathway has been proposed as a molecular regulator of emotional memories and could thus constitute a common mechanistic source of the emergence of anxiety symptoms in these disorders. We hypothesize that amygdala mTOR dysfunction during infancy can initiate a

Autism spectrum disorder (ASD) is a complex and highly prevalent neurodevelopmental disorder. ASD exhibits significant heterogeneity in genotypes and phenotypes. In recent years, dysregulation of protein synthesis has emerged as a converging mechanism in ASD. Here, to explore altered translation in ASD, we used induced pluripotent stem cells (iPSCs) which have emerged as a promising cellular tool for disease modeling. Patient relevant mutations in FMR1, PTEN, and TSC2, that cause dysregulated protein synthesis, were introduced into iPSCs derived from healthy donors via CRISPR/Cas9. Then, iPSCs

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