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

Molecular Psychiatry volume 24, pages 643–652 (2019)Cite this article

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Abstract

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/β-catenin pathway is one of the major pathways involved. The canonical WNT/β-catenin pathway participates in the development of the central nervous system, and its dysregulation involves developmental cognitive disorders. In numerous tissues, the canonical WNT/β-catenin pathway and peroxisome proliferator-activated receptor gamma (PPARγ) act in an opposed manner. In ASD, the canonical WNT/β-catenin pathway is increased while PPARγ seems to be decreased. PPARγ agonists present a beneficial effect in treatment for ASD children through their anti-inflammatory role. Moreover, they induce the inhibition of the canonical WNT/β-catenin pathway in several pathophysiological states. We focus this review on the hypothesis of an opposed interplay between PPARγ and the canonical WNT/β-catenin pathway in ASD and the potential role of PPARγ agonists as treatment for ASD.

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Authors and Affiliations

  1. Paris-Descartes University; Diagnosis and Therapeutic Center, Hôtel-Dieu Hospital; AP-HP, Paris, France

    Alexandre Vallée

  2. Centre Hospitalier Universitaire (CHU) Amiens Picardie, Université Picardie Jules Verne (UPJV), 80054, Amiens, France

    Jean-Noël Vallée

  3. Laboratoire de Mathématiques et Applications (LMA), UMR CNRS 7348, Université de Poitiers, Poitiers, France

    Alexandre Vallée & Jean-Noël Vallée

  4. Centre de Recherche Clinique, Grand Hôpital de l’Est Francilien (GHEF), 6-8 rue Saint-fiacre, 77100, Meaux, France

    Yves Lecarpentier

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  1. Alexandre Vallée
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Vallée, A., Vallée, JN. & Lecarpentier, Y. PPARγ agonists: potential treatment for autism spectrum disorder by inhibiting the canonical WNT/β-catenin pathway. Mol Psychiatry 24, 643–652 (2019). https://doi.org/10.1038/s41380-018-0131-4

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