These results identify a novel mechanistic link between mTOR and orexin in the hypothalamus related to sleep dysfunction and suggest a targeted therapeutic approach to sleep disorders in TSC.
Adipocyte-specific Raptor KO mice experienced exacerbated alcohol-induced steatosis, but neither adipocyte-specific mTOR nor adipocyte-specific tuberous sclerosis complex 1 KO mice exhibited similar detrimental effects.
Because of its effect on the mTOR pathway, there may be a role for metformin in slowing or reversing growth of life-threatening hamartomas in tuberous sclerosis complex.
A broad spectrum of malformations of cortical development, such as focal cortical dysplasia (FCD) and tuberous sclerosis complex (TSC), have been linked to either germline or somatic mutations in mTOR pathway-related genes, commonly summarised under the umbrella term 'mTORopathies'.
The advent of mTOR inhibitors offers great promise in the treatment of TSC-associated epilepsy and other neurodevelopmental manifestations of the disease; however, the optimal timing of therapeutic intervention is not yet fully understood.
Tuberous sclerosis complex (TSC) is a rare neurodevelopmental disorder resulting from autosomal dominant mutations in the TSC1 or TSC2 genes, leading to a hyperactivated mammalian target of rapamycin (mTOR) pathway, and gray and white matter defects in the brain.
To investigate whether mammalian target of rapamycin inhibitor everolimus can improve intellectual disability, autism, and other neuropsychological deficits in children with tuberous sclerosis complex (TSC).
Hamartin, a component of the tuberous sclerosis complex (TSC) that actively inhibits the mammalian target of rapamycin (mTOR), may mediate the endogenous resistance of Cornu Ammonis 3 (CA3) hippocampal neurons following global cerebral ischemia.
Protocolled treatment of TSC-associated epilepsy with the mTOR inhibitor everolimus has recently been approved by The Danish Medicines Council in Denmark.
The decrease in CD4<sup>+</sup> T-cell survival following fungal sepsis was ameliorated in mice with a T-cell-specific mTOR deletion, whereas it was exacerbated in mice with a T-cell-specific tuberous sclerosis complex (TSC)1 deletion.
Various tumors and hamartomas affecting different organs are the pathological hallmarks of the disease, especially cortical tubers of the brain, but specific cellular and molecular abnormalities, such as involving the mechanistic target of rapamycin (mTOR) pathway, have been identified that also cause or contribute to neurological manifestations of TSC independent of gross structural lesions.
Here, we further examined whether hypervascularization occurs in animal models of global and focal MCD with and without seizures, and whether it is sensitive to the mTOR blocker, rapamycin, that is approved for epilepsy treatment in tuberous sclerosis complex.
These data demonstrate that neuronal mTOR hyperactivity levels influence the severity of epilepsy and associated neuropathology in experimental TSC and FCD.
Also included is the utilization of mTOR inhibitors in both advanced renal cell carcinoma (RCC) and in patients with tuberous sclerosis complex (TSC) associated angiomyolipoma (AML).
Trials of mTOR inhibitors in tuberous sclerosis complex have demonstrated that inhibition of mTOR activation in mTORopathies can reduce seizure frequency.
Loss of the Pten (phosphatase and tensin homolog) gene has been demonstrated to result in hyperactivation of the mammalian target of rapamycin (mTOR) pathway, a signaling pathway common to many disease etiologies, including tuberous sclerosis complex, Fragile X syndrome, and schizophrenia.
In tuberous sclerosis (TSC)-associated tumors, mutations in the TSC genes lead to aberrant activation of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway. mTORC1 signaling impacts many biological processes including the epithelial-mesenchymal transition (EMT), which is suggested to promote tumor progression and metastasis in various types of cancer.