Synaptopathology Involved in Autism Spectrum Disorder

Autism spectrum disorder (ASD) encompasses a group of multifactorial neurodevelopmental disorders characterized by impaired social communication, social interaction and repetitive behaviors. ASD affects 1 in 59 children, and is about 4 times more common among boys than among girls. Strong genetic components, together with environmental factors in the early stage of development, contribute to the pathogenesis of ASD. Multiple studies have revealed that mutations in genes like NRXN, NLGN, SHANK, TSC1/2, FMR1, and MECP2 converge on common cellular pathways that intersect at synapses. These genes encode cell adhesion molecules, scaffolding proteins and proteins involved in synaptic transcription, protein synthesis and degradation, affecting various aspects of synapses including synapse formation and elimination, synaptic transmission and plasticity. This suggests that the pathogenesis of ASD may, at least in part, be attributed to synaptic dysfunction. In this article, we will review major genes and signaling pathways implicated in synaptic abnormalities underlying ASD, and discuss molecular, cellular and functional studies of ASD experimental models.