Tuberous sclerosis complex

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

…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

Tuberous sclerosis complex (TSC) is a genetic disorder caused by mutations in TSC1/2 genes, leading to mTOR pathway dysregulation and diverse cellular impacts. Individuals with TSC face severely heightened risk of autism spectrum disorder (ASD), highlighting a genetic link between the two conditions. To model ASD etiology in the context of TSC, we developed a new mouse model with Tsc2 knockout induced mid-gestation in all postmitotic, GABAergic neurons. As ASD and TSC both involve somatosensory processing challenges, we utilized our mouse model to assess how the mutation affects the cortical a

…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

Tuberous sclerosis complex (TSC) is a genetic disorder where many patients affected by the disease suffer from refractive epilepsy. To alleviate related symptoms, the patients must undergo surgery to resect the epileptogenic lesion. Obtaining this tissue and instantly flash freeze it provides a unique opportunity to gain insight to the pathogenesis of TSC.Thus, we embarked on an in-depth unbiased characterization of the transcriptomic landscape, cellular identify, and potential epileptogenic networks of frontal cortical tubers of pediatric TSC using snRNA-seq on resected epileptic tissue and c

Epilepsy is one of the most common neurological diseases according to the World Health Organization (WHO) affecting around 70 million people worldwide [WHO]. Patients who suffer from epilepsy also suffer from a variety of neuro-psychiatric co-morbidities, which they can experience as crippling as the seizure condition itself. Adequate organization of cerebral white matter is utterly important for cognitive development. The failure of integration of neurologic function with cognition is reflected in neuro-psychiatric disease, such as autism spectrum disorder (ASD). However, in epilepsy we know

Epilepsy is one of the most common neurological diseases according to the World Health Organization (WHO) affecting around 70 million people worldwide [WHO]. Patients who suffer from epilepsy also suffer from a variety of neuro-psychiatric co-morbidities, which they can experience as crippling as the seizure condition itself. Adequate organization of cerebral white matter is utterly important for cognitive development. The failure of integration of neurologic function with cognition is reflected in neuro-psychiatric disease, such as autism spectrum disorder (ASD). However, in epilepsy we know

Tuberous sclerosis complex (TSC) and focal cortical dysplasia type II (FCDII) are caused by mutations in mTOR pathway genes leading to mTOR hyperactivity, focal malformations of cortical development (fMCD), and seizures in 80-90% of the patients. The current definitive treatments for epilepsy are surgical resection or treatment with everolimus, which inhibits mTOR activity (only approved for TSC). Because both options have severe limitations, there is a major need to better understand the mechanisms leading to seizures to improve life-long epilepsy treatment in TSC and FCDII. To investigate su