Abstract
Tuberous sclerosis complex (TSC) is a multisystem disorder that affects numerous organ systems. Brain lesions that form during development, known as tubers, are highly associated with epilepsy, cognitive disability, and autism. Following the identification of two genes and their encoded proteins, TSC1 (hamartin) and TSC2 (tuberin), responsible for TSC, identification of several downstream protein cascades that might be affected in TSC have been discovered. Of primary importance is the mammalian target of rapamycin pathway that controls cell growth and protein synthesis. The mechanisms governing brain lesion growth have not been fully identified but likely altered regulation of the mammalian target of rapamycin cascade by hamartin and tuberin during development leads to aberrant cell growth. Secondary effects of TSC gene mutations might disrupt normal neuronal migration and cerebral cortical lamination. Numerous studies have identified changes in gene and protein expression in animal models of TSC and in human TSC brain specimens that contribute to altered brain cytoarchitecture. This review will provide an overview of the neurobiological aspects of TSC.
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Marcotte, L., Crino, P.B. The neurobiology of the tuberous sclerosis complex. Neuromol Med 8, 531–546 (2006). https://doi.org/10.1385/NMM:8:4:531
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DOI: https://doi.org/10.1385/NMM:8:4:531