Authors: Switon K., Kotulska K., Janusz-Kaminska A., Zmorzynska J., Jaworski J.

International Union of Biochemistry and Molecular Biology 68:12, 955-962, Dec 2016. 


Tuberous sclerosis complex (TSC) is a rare multi-system disorder, primary manifestations of which are benign tumors and lesions in various organs of the body, including the brain. TSC patients offer suffer from epilepsy, mental retardation, and autism spectrum disorders (ASD). Therefore, TSC serves as a model of epilepsy, ASD, and tumorigenesis. TSC is caused by the lack of function Tsc1-Tsc2 complex, which serves as a major cellular inhibitor of Mammalian Target of Rapamycin Complex 1 (mTORC1). mTORC1 is a kinase controlling most of anabolic processes in eukaryotic cells. Consequently, mTORC1 inhibitors, such as rapaymcin, serve as experimental or already approved drugs for several TSC symptoms. However rapalogs, although quite effective, need to be administered chronically and likely for a lifetime, since therapy discontinuation results in tumor regrowth and epilepsy recurrence. Recent studies revealed that metabolism and excitability (in the case of neurons) of cells lacking Tsc1-Tsc2 complex are changed and these features may potentially be used to treat some of TSC symptoms. In this review, we first provide basic facts about TSC and its molecular background, to next discuss the newest findings in TSC cell biology that can be used to improve existing therapies of TSC and other diseases linked to mTORC1 hyperactivation.