PPARγ agonists: potential treatment for autism spectrum disorder by inhibiting the canonical WNT/β-catenin pathway

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is characterized by a deficit in social interactions and communication with repetitive and restrictive behavior. No curative treatments are available for ASD. Pharmacological treatments do not address the core ASD behaviors, but target comorbid symptoms. Dysregulation of the core neurodevelopmental pathways is associated with the clinical presentation of ASD, and the canonical WNT/beta-catenin pathway is one of the major pathways involved. The canonical WNT/beta-catenin pathway participates in the development of the central nervous system, and its dysregulation involves developmental cognitive disorders. In numerous tissues, the canonical WNT/beta-catenin pathway and peroxisome proliferator-activated receptor gamma (PPAR gamma) act in an opposed manner. In ASD, the canonical WNT/beta-catenin pathway is increased while PPAR gamma seems to be decreased. PPAR gamma agonists present a beneficial effect in treatment for ASD children through their anti-inflammatory role. Moreover, they induce the inhibition of the canonical WNT/beta-catenin pathway in several pathophysiological states. We focus this review on the hypothesis of an opposed interplay between PPAR gamma and the canonical WNT/beta-catenin pathway in ASD and the potential role of PPAR gamma agonists as treatment for ASD.