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Tuberous Sclerosis: A New Frontier in Targeted Treatment of Autism

NEUROTHERAPEUTICS (2015)

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期刊

NEUROTHERAPEUTICS
卷 12, 期 3, 页码 572-583

出版社

SPRINGER
DOI: 10.1007/s13311-015-0359-5

关键词

mTOR; translation; white matter; cerebellum

类别

Clinical Neurology Neurosciences Pharmacology & Pharmacy

资金

  1. National Institutes of Health (NIH) National Institute of Neurological Disorders and Stroke (NINDS) [3R25NS070682-04S1]
  2. NIH [U01 NS082320, P20 NS080199, U54NS092090, P30 HD018655]
  3. NCATS
  4. National Institute of Mental Health
  5. NINDS
  6. National Institute of Child Health and Human Development
  7. Harvard Catalyst \ The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH) [UL1 TR001102]
  8. Tuberous Sclerosis Alliance
  9. Clack Foundation
  10. Novartis
  11. Upsher-Smith
  12. Department of Defense
  13. Autism Speaks
  14. Nancy Lurie Marks Family Foundation
  15. Simons Foundation
  16. Boston Children's Hospital Translational Research Program
  17. Shire
  18. Roche

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Tuberous sclerosis complex (TSC) is a genetic disorder with a high prevalence of autism spectrum disorder (ASD). Tremendous progress in understanding the pathogenesis of TSC has been made in recent years, along with initial trials of medical treatment aimed specifically at the underlying mechanism of the disorder. At the cellular level, loss of TSC1 or TSC2 results in upregulation of the mechanistic target of rapamycin (mTOR) pathway. At the circuitry level, TSC and mTOR play crucial roles in axonal, dendritic, and synaptic development and function. In this review, we discuss the molecular mechanism underlying TSC, and how this disease results in aberrant neural connectivity at multiple levels in the central nervous system, leading to ASD symptoms. We then review recent advances in mechanism-based treatments of TSC, and the promise that these treatments provide for future mechanism-based treatment of ASD. Because of these recent advances, TSC represents an ideal model for how to make progress in understanding and treating the mechanisms that underlie ASD in general.

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