Acta Neuropathologica

, Volume 125, Issue 3, pp 317–332

Evolving neurobiology of tuberous sclerosis complex

Review
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Abstract

Over the past decade, there have been numerous advances in our understanding of the molecular pathogenesis of tuberous sclerosis complex (TSC). Following the identification of the TSC1 and TSC2 genes, a link to regulatory control of the mammalian target of rapamycin (mTOR) signaling pathway has paved the way for new therapeutic interventions, and now even approved therapies for TSC. Gene identification has permitted establishment of cell lines and conditional knockout mouse strains to assay how abnormalities in brain structure lead to enhanced excitability, seizures, cognitive disabilities, and other neuropsychological disorders in TSC. Furthermore, work in in vitro systems and analysis of rodent models and human tissue has allowed investigators to study how brain lesions form in TSC. Evolving questions over the next decade include understanding the high clinical variability of TSC, defining why there is a lack of clear genotype–phenotype correlations, and identifying biomarkers for prognosis and stratification. The study of TSC has in many ways reflected a paradigm “bench-to-bedside” success story that serves as a model of many other neurological disorders.

Keywords

Tuberous sclerosis mTOR Epilepsy Autism Tuber SEGA 

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Department of NeurologyShriners Hospitals Pediatric Research Center, Temple University School of MedicinePhiladelphiaUSA

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