Synaptic Dysfunction in Neurodevelopmental Disorders Associated with Autism and Intellectual Disabilities

  1. Mark F. Bear2
  1. 1Howard Hughes Medical Institute, The Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, Texas 77030; and Department of Neuroscience and Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030
  2. 2Howard Hughes Medical Institute, Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
  1. Correspondence: hzoghbi{at}bcm.edu; mbear{at}mit.edu

Abstract

The discovery of the genetic causes of syndromic autism spectrum disorders and intellectual disabilities has greatly informed our understanding of the molecular pathways critical for normal synaptic function. The top-down approaches using human phenotypes and genetics helped identify causative genes and uncovered the broad spectrum of neuropsychiatric features that can result from various mutations in the same gene. Importantly, the human studies unveiled the exquisite sensitivity of cognitive function to precise levels of many diverse proteins. Bottom-up approaches applying molecular, biochemical, and neurophysiological studies to genetic models of these disorders revealed unsuspected pathogenic mechanisms and identified potential therapeutic targets. Moreover, studies in model organisms showed that symptoms of these devastating disorders can be reversed, which brings hope that affected individuals might benefit from interventions even after symptoms set in. Scientists predict that insights gained from studying these rare syndromic disorders will have an impact on the more common nonsyndromic autism and mild cognitive deficits.



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      1. Cold Spring Harb. Perspect. Biol. 4: a009886 Copyright © 2012 Cold Spring Harbor Laboratory Press; all rights reserved

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