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Curr Neuropharmacol. 2014 Jan;12(1):71-98. doi: 10.2174/1570159X113116660046.

The role of ionotropic glutamate receptors in childhood neurodevelopmental disorders: autism spectrum disorders and fragile x syndrome.

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Autism and Obsessive Compulsive Spectrum Program, Department of Psychiatry, Montefiore Medical Center, Albert Einstein College of Medicine, 111 East 210th St, Bronx, New York 10467-2490;
Department of Neurobiology and Anatomy, University of Utah School of Medicine, 531A Wintrobe, 20N 1900 E, Salt Lake City, Utah 84132.


Autism spectrum disorder (ASD) and Fragile X syndrome (FXS) are relatively common childhood neurodevelopmental disorders with increasing incidence in recent years. They are currently accepted as disorders of the synapse with alterations in different forms of synaptic communication and neuronal network connectivity. The major excitatory neurotransmitter system in brain, the glutamatergic system, is implicated in learning and memory, synaptic plasticity, neuronal development. While much attention is attributed to the role of metabotropic glutamate receptors in ASD and FXS, studies indicate that the ionotropic glutamate receptors (iGluRs) and their regulatory proteins are also altered in several brain regions. Role of iGluRs in the neurobiology of ASD and FXS is supported by a weight of evidence that ranges from human genetics to in vitro cultured neurons. In this review we will discuss clinical, molecular, cellular and functional changes in NMDA, AMPA and kainate receptors and the synaptic proteins that regulate them in the context of ASD and FXS. We will also discuss the significance for the development of translational biomarkers and treatments for the core symptoms of ASD and FXS.


AMPA receptor; Arc; Fragile X syndrome; GRIP1/2; MAP1B; NMDA receptor.; autism spectrum disorder; kainate receptor; memantine; metabotropic glutamate receptor; neuroligin

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