Unraveling the Role of Neuroligin3 in Autism Spectrum Disorders: Pathophysiological Insights and Targeted Therapies

Autism Spectrum Disorder is a neurodevelopmental disorder characterized by impaired social and communication skills, repetitive behaviors, and/or restricted interests with a prevalence of as high as 1% of children. Autism spectrum has strongly associated with genetic factors and exhibits wide clinical and heterogeneous genetic architecture. Most genes associated with Autism are involved in neuronal and synaptic development. The neuroligin3, the sex-linked gene on the X chromosome, was the first gene to be associated with a monogenic form of Autism. Neuroligin3 is a postsynaptic cell adhesion protein involved in synapse transmission, brain formation, and neuronal development. In this review, we provide recent findings on different mutations in the Neuroligin3 gene linked to Autism spectrum disorder and their molecular pathway effect. We also give the behavioral, and synaptic alterations reported in the Neuroligin3 animal model of Autism and the potential therapeutic strategies targeting the biological processes and the main symptoms of autism spectrum disorder. In addition, we discuss the use of novel technologies like induced pluripotent stem cells from Autistic patients that have the potential to differentiate in human neurons and therefore have a variety of applications in therapy and biomedical studies to search specific biomarkers, and develop systems for screening chemical molecules in human cells to discover target therapies.