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http://dx.doi.org/10.1016/j.celrep.2022.110563 | DOI Listing |
Orphanet J Rare Dis
January 2025
Division of Pediatric Epileptology, Department of Pediatrics I, Medical Faculty of Heidelberg, Heidelberg University, Heidelberg, Germany.
Background: Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder affecting multiple organ systems, with a prevalence of 1:6,760-1:13,520 live births in Germany. On the molecular level, TSC is caused by heterozygous loss-of-function variants in either of the genes TSC1 or TSC2, encoding the Tuberin-Hamartin complex, which acts as a critical upstream suppressor of the mammalian target of rapamycin (mTOR), a key signaling pathway controlling cellular growth and metabolism. Despite the therapeutic success of mTOR inhibition in treating TSC-associated manifestations, studies with mTOR inhibitors in children with TSC above two years of age have failed to demonstrate beneficial effects on disease-related neuropsychological deficits.
View Article and Find Full Text PDFFront Behav Neurosci
December 2024
Department of Biology, Miami University, Oxford, OH, United States.
Angiogenesis
December 2024
Division of Vascular Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, 171 77, Sweden.
Hum Pathol
November 2024
Department of Pathology, Johns Hopkins School of Medicine, USA; Department of Urology, Johns Hopkins School of Medicine, USA; Department of Oncology, Johns Hopkins School of Medicine, USA. Electronic address:
Sci Adv
November 2024
Cancer Program, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia.
Tuberous sclerosis complex (TSC) is targeted to the lysosomal membrane, where it hydrolyzes RAS homolog-mTORC1 binding (RHEB) from its GTP-bound to GDP-bound state, inhibiting mechanistic target of rapamycin complex 1 (mTORC1). Loss-of-function mutations in TSC cause TSC disease, marked by excessive tumor growth. Here, we overcome a high degree of continuous conformational heterogeneity to determine the 2.
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