The role of neurexins in schizophrenia and autistic spectrum disorder

Schizophrenia and autistic spectrum disorder (ASD) are common, chronic mental conditions with both genetic and environmental components to their aetiology. The identification of genes influencing susceptibility to these disorders offers a rational route towards a clearer understanding of the neurobiology, and with this the prospect of treatment and prevention strategies tailored towards the remediation of the altered pathways. Copy number variants (CNVs) underlie many serious illnesses, including neurological and neurodevelopmental syndromes. Recent studies assessing copy number variation in ASD and schizophrenia have repeatedly observed heterozygous deletions eliminating exons of the neurexin-1 alpha gene (but not the neurexin-1 beta gene) in patients with ASD and schizophrenia. The neurexins are synaptic adhesion proteins that are known to play a key role in synaptic formation and maintenance. The functional significance of the recurrent deletion is poorly understood, but the availability of mice with deletion of the promoter and first exon of neurexin-1 alpha provides direct access to the biological effects of neurexin-1 alpha disruption on phenotypes relevant to ASD and schizophrenia. We review the evidence for the role of neurexin-1 alpha in schizophrenia and ASD, and consider how genetic disruption of neurexin-1 alpha may underpin the neuropathology contributing to these distinct neurodevelopmental disorders. This article is part of a Special Issue entitled 'Schizophrenia'. (C) 2011 Elsevier Ltd. All rights reserved.