Unraveling the Role of Wnt Signaling Pathway in the Pathogenesis of Autism Spectrum Disorder (ASD): A Systematic Review.

This review looked at how problems with a specific biological pathway (called Wnt signaling) might contribute to autism. Researchers found that when this pathway doesn't work properly, it can affect brain development and function in ways that may lead to autism symptoms. Importantly, some medications that target this pathway showed promise in reducing autism-like behaviors in animal studies, suggesting new treatment possibilities.

This systematic review examined the role of Wnt signaling pathway in autism spectrum disorder (ASD) pathogenesis through analysis of animal model studies. The Wnt pathway regulates critical developmental processes including cell fate determination, migration, neural patterning, and organogenesis. The review found evidence linking Wnt pathway dysregulation to autism-related abnormalities affecting energy metabolism, oxidative stress, and neurogenesis. These alterations may underlie autistic behaviors by impacting synaptic transmission and mitochondrial function.

Neuropharmacological studies demonstrated that drugs targeting the Wnt pathway, such as Canagliflozin, can reduce autistic-like behaviors in animal models, suggesting potential therapeutic applications. The findings highlight the Wnt pathway as a promising target for future autism interventions.

Findings suggest Wnt pathway dysregulation as a potential therapeutic target for autism. However, translation from animal models to human treatments requires further research. The identified pathway abnormalities may help explain biological mechanisms underlying autism symptoms and guide future intervention development.

Study limited to animal models only. No sample size reported for the systematic review. Clinical translation of animal findings to humans remains uncertain. Quality of included studies assessed but specific methodological concerns not detailed in abstract.

Autism spectrum disorder (ASD), or simply autism, is a neurodevelopmental disorder characterized by social communication deficit, restricted interests, and repetitive behavior. Several studies suggested a link between autism and the dysregulation of the Wnt signaling pathway which is mainly involved in cell fate determination, cell migration, cell polarity, neural patterning, and organogenesis. Despite the absence of effective therapy, significant progress has been made in understanding the pathogenesis of ASD. Neuropharmacological studies showed that drugs acting on the Wnt pathway like Canagliflozin can alleviate autistic-like behavior in animal models.

Hence, this pathway could potentially be a futuristic therapeutic target to mitigate autism's symptoms. This systematic review aims to collect and analyze evidence that elucidates how alterations in the Wnt pathway may contribute to the pathogenesis of autism in animal models at the molecular, cellular, and physiological levels. Comprehensive searches were conducted across multiple databases, including PubMed, Web of Science, Embase, and Scopus to identify relevant studies up to March 2024. The inclusion criteria encompassed experimental studies that focused on the link between autism and this pathway, and the quality assessment was ensured by SYRCLE's risk of bias tools.

Collectively, the included articles highlighted the possible implication of this pathway in the abnormalities found in autism, which impacted processes such as energy metabolism, oxidative stress, and neurogenesis. These alterations could underlie autistic behavior by affecting synaptic transmission and mitochondrial function.