Alexander Jacob, Keles Gizem, Killingsworth Jessica, Bronson Ronald, Perez Christine, Sawmiller Darrell, Shytle R Douglas
San Juan Bautista School of Medicine, Expreso Luis A. Ferré, Caguas 00727, PR, United States.
Department of Neurosurgery and Brain Repair, Morsani College of Medicine, USF Health, 12901 Bruce B Downs Blvd, Tampa, FL, USA.
Exp Neurol. 2022 Jul;353:114050. doi: 10.1016/j.expneurol.2022.114050. Epub 2022 Mar 17.
Developmental disabilities are defined as disorders that result in the limitation of function due to impaired development of the nervous system; these disabilities can be present in the form of impairments in learning, language, behavior, or physical abilities. Examples of developmental disorders include attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), cerebral palsy (CP), hearing loss, blindness, intellectual disability, and learning disability. Of these disorders, ASD prevalence was 18.5 per 1000 children (1 in 54) aged 8 in 2016. Current literature suggests that deficient levels of heparan sulfate (HS), an acidic and linear glycosaminoglycan (GAG), is likely causative of ASD. The cascading effect of deficient HS levels can offer compelling evidence for the association of HS with ASD. Deficient levels of HS lead to defective Slit/Robo signaling, which affects axonal guidance and dendritic spine formation. Defective Slit/Robo signaling leads to increased Arp2/3 activity and dendritic spine density, which has been observed in the brains of persons with ASD. Therefore, interventions that target HS and its associated pathways may be viable treatment options for ASD.