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Evolving neurobiology of tuberous sclerosis complex

Acta Neuropathologica volume 125, pages 317–332 (2013)Cite this article

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.

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Acknowledgments

This work was supported by NS045021, Department of Defense CDMRP-TSC Program grants, and the TS Alliance.

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  1. Department of Neurology, Shriners Hospitals Pediatric Research Center, Temple University School of Medicine, 6th Floor Medical Education and Research Building, 3500N. Broad Street, Philadelphia, PA, 19140-4106, USA

    Peter B. Crino

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Crino, P.B. Evolving neurobiology of tuberous sclerosis complex. Acta Neuropathol 125, 317–332 (2013). https://doi.org/10.1007/s00401-013-1085-x

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Keywords

  • Tuberous sclerosis
  • mTOR
  • Epilepsy
  • Autism
  • Tuber
  • SEGA