The influence of circadian rhythms and aerobic glycolysis in autism spectrum disorder

Abstract Intellectual abilities and their clinical presentations are extremely heterogeneous in autism spectrum disorder (ASD). The main causes of ASD remain unclear. ASD is frequently associated with sleep disorders. Biologic rhythms are complex systems interacting with the environment and controlling several physiological pathways, including brain development and behavioral processes. Recent findings have shown that the deregulation of the core clock neurodevelopmental signaling is correlated with ASD clinical presentation. One of the main pathways involved in developmental cognitive disorders is the canonical WNT/β-catenin pathway. Circadian clocks have a main role in some tissues by driving circadian expression of genes involved in physiologic and metabolic functions. In ASD, the increase of the canonical WNT/β-catenin pathway is enhancing by the dysregulation of circadian rhythms. ASD progression is associated with a major metabolic reprogramming, initiated by aberrant WNT/β-catenin pathway, the aerobic glycolysis. This review focuses on the interest of circadian rhythms dysregulation in metabolic reprogramming in ASD through the aberrant upregulation of the canonical WNT/β-catenin pathway.