Brain Symptoms of Tuberous Sclerosis Complex: Pathogenesis and Treatment

The mammalian target of the rapamycin (mTOR) system plays multiple, important roles in the brain, regulating both morphology, such as cellular size, shape, and position, and function, such as learning, memory, and social interaction. Tuberous sclerosis complex (TSC) is a congenital disorder caused by a defective suppressor of the mTOR system, the TSC1/TSC2 complex. Almost all brain symptoms of TSC are manifestations of an excessive activity of the mTOR system. Many children with TSC are afflicted by intractable epilepsy, intellectual disability, and/or autism. In the brains of infants with TSC, a vicious cycle of epileptic encephalopathy is formed by mTOR hyperactivity, abnormal synaptic structure/function, and excessive epileptic discharges, further worsening epilepsy and intellectual/behavioral disorders. Molecular target therapy with mTOR inhibitors has recently been proved to be efficacious for epilepsy in human TSC patients, and for autism in TSC model mice, indicating the possibility for pharmacological treatment of developmental synaptic disorders.

Automated summary

The mTOR system in the brain plays crucial roles in regulating morphology and function, with Tuberous sclerosis complex (TSC) being a congenital disorder caused by defects in the mTOR system suppressor complex. Most brain symptoms of TSC are due to excessive mTOR system activity, leading to conditions such as epilepsy, intellectual disability, and autism. Recent studies have shown that molecular target therapy with mTOR inhibitors can effectively treat epilepsy in human TSC patients and autism in TSC model mice, presenting the potential for pharmacological treatment of developmental synaptic disorders.