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Contactins in the neurobiology of autism.

Abstract
Autism is a disease of brain plasticity. Inspiring work of Willem Hendrik Gispen on neuronal plasticity has stimulated us to investigate gene defects in autism and the consequences for brain development. The central process in the pathogenesis of autism is local dendritic mRNA translation which is dependent on axodendritic communication. Hence, most autism-related gene products (i) are part of the protein synthesis machinery itself, (ii) are components of the mTOR signal transduction pathway, or (iii) shape synaptic activity and plasticity. Accordingly, prototype drugs have been recognized that interfere with these pathways. The contactin (CNTN) family of Ig cell adhesion molecules (IgCAMs) harbours at least three members that have genetically been implicated in autism: CNTN4, CNTN5, and CNTN6. In this chapter we review the genetic and neurobiological data underpinning their role in normal and abnormal development of brain systems, and the consequences for behavior. Although data on each of these CNTNs are far from complete, we tentatively conclude that these three contactins play roles in brain development in a critical phase of establishing brain systems and their plasticity. They modulate neuronal activities, such as neurite outgrowth, synaptogenesis, survival, guidance of projections and terminal branching of axons in forming neural circuits. Current research on these CNTNs concentrate on the neurobiological mechanism of their developmental functions. A future task will be to establish if proposed pharmacological strategies to counteract ASD-related symptomes can also be applied to reversal of phenotypes caused by genetic defects in these CNTN genes.
AuthorsAmila Zuko, Kristel T E Kleijer, Asami Oguro-Ando, Martien J H Kas, Emma van Daalen, Bert van der Zwaag, J Peter H Burbach
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 719 Issue 1-3 Pg. 63-74 (Nov 05 2013) ISSN: 1879-0712 [Electronic] Netherlands
PMID23872404 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
Copyright© 2013 Elsevier B.V. All rights reserved.
Chemical References
  • Contactins
Topics
  • Animals
  • Child Development Disorders, Pervasive (genetics, metabolism, pathology)
  • Contactins (genetics, metabolism)
  • Gene Expression Regulation
  • Humans
  • Neurobiology
  • Neurons (pathology)

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