1
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Targeted treatments for cognitive and neurodevelopmental disorders in tuberous sclerosis complex

      review-article
      Neurotherapeutics
      Springer-Verlag
      TSC, mTOR, rapamycin, neurocognition, memory, autism, autism spectrum disorders

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Summary

          Until recently, the neuropsychiatric phenotype of tuberous sclerosis complex (TSC) was presumed to be caused by the structural brain abnormalities and/or seizures seen in the disorder. However, advances in the molecular biology of the disorder have shown that TSC is a mammalian target of rapamycin (mTOR) overactivation syndrome, and that direct molecular pathways exist between gene mutation and cognitive/neurodevelopmental phenotype. Molecularly-targeted treatments using mTOR inhibitors (such as rapamycin) are showing great promise for the physical and neurological phenotype of TSC. Pre-clinical and early-phase clinical studies of the cognitive and neurodevelopmental features of TSC suggest that some of the neuropsychiatric phenotypes might also be reversible, even in adults with the disorder. TSC, fragile X, neurofibromatosis type 1, and disorders associated with phosphatase and tensin homo (PTEN) mutations, all signal through the mTOR signaling pathway, with the TSC1-TSC2 protein complex as a molecular switchboard at its center. Together, these disorders represent as much as 14% of autism spectrum disorders (ASD). Therefore, we suggest that this signaling pathway is a key to the underlying pathophysiology of a significant subset of individuals with ASD. The study of molecularly targeted treatments in TSC and related disorders, therefore, may be of scientific and clinical value not only to those with TSC, but to a larger population that may have a neuropsychiatric phenotype attributable to mTOR overactivation or dysregulation.

          Related collections

          Author and article information

          Contributors
          pd215@cam.ac.uk
          Journal
          Neurotherapeutics
          Neurotherapeutics
          Neurotherapeutics
          Springer-Verlag (New York )
          1933-7213
          1878-7479
          July 2010
          : 7
          : 3
          : 275-282
          Affiliations
          grid.5335.00000000121885934Neurodevelopmental Service (NDS), Cambridgeshire & Peterborough NHS Foundation Trust & Developmental Psychiatry Section, University of Cambridge, CB2 8AH Cambridge, UK
          Article
          PMC5084231 PMC5084231 5084231 70300275
          10.1016/j.nurt.2010.05.001
          5084231
          20643380
          ecfc29e4-229c-4d93-82b0-7b6afe1f0fd7
          © Springer 2010
          History
          Categories
          Review Article
          Custom metadata
          © Springer 2010

          autism,autism spectrum disorders,memory,neurocognition,rapamycin,mTOR,TSC

          Comments

          Comment on this article