Paris-Descartes University; Diagnosis and Therapeutic Center, Hôtel-Dieu Hospital; AP-HP, Paris, France.
Laboratoire de Mathématiques et Applications (LMA), UMR CNRS 7348, Université de Poitiers, Poitiers, France.
Mol Psychiatry. 2019 May;24(5):643-652. doi: 10.1038/s41380-018-0131-4. Epub 2018 Aug 13.
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.
自闭症谱系障碍 (ASD) 是一种神经发育障碍，其特征是社交互动和沟通能力缺陷，以及重复和受限的行为。目前尚无针对 ASD 的治愈方法。药物治疗不能解决 ASD 的核心行为问题，而是针对共病症状。核心神经发育途径的失调与 ASD 的临床表现有关，而经典 WNT/β-连环蛋白途径是涉及的主要途径之一。经典 WNT/β-连环蛋白途径参与中枢神经系统的发育，其失调涉及发育性认知障碍。在许多组织中，经典 WNT/β-连环蛋白途径和过氧化物酶体增殖物激活受体 γ (PPARγ) 以相反的方式发挥作用。在 ASD 中，经典 WNT/β-连环蛋白途径增加，而 PPARγ 似乎减少。PPARγ 激动剂通过其抗炎作用在 ASD 儿童的治疗中表现出有益的效果。此外，它们在几种病理生理状态下诱导经典 WNT/β-连环蛋白途径的抑制。我们专注于 PPARγ 和经典 WNT/β-连环蛋白途径在 ASD 中的相反相互作用的假设，以及 PPARγ 激动剂作为 ASD 治疗的潜在作用。
