Bou Najm Daniel, Alame Saada, Takash Chamoun Wafaa
Neuroscience Research Center, Faculty of Medical Sciences, Lebanese University, Hadath, Lebanon.
Faculty of Medical Sciences, Lebanese University, Hadath, Lebanon.
Mol Neurobiol. 2025 Apr;62(4):4971-4992. doi: 10.1007/s12035-024-04558-x. Epub 2024 Nov 4.
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.
自闭症谱系障碍（ASD），或简称为自闭症，是一种神经发育障碍，其特征为社交沟通缺陷、兴趣受限和重复行为。多项研究表明自闭症与Wnt信号通路失调之间存在关联，该信号通路主要参与细胞命运决定、细胞迁移、细胞极性、神经模式形成和器官发生。尽管缺乏有效的治疗方法，但在理解ASD的发病机制方面已取得了重大进展。神经药理学研究表明，像卡格列净这样作用于Wnt通路的药物可以减轻动物模型中的自闭症样行为。因此，该通路可能成为减轻自闭症症状的未来治疗靶点。本系统综述旨在收集和分析证据，以阐明Wnt通路的改变如何在分子、细胞和生理水平上导致动物模型中自闭症的发病机制。在包括PubMed、Web of Science、Embase和Scopus在内的多个数据库中进行了全面检索，以识别截至2024年3月的相关研究。纳入标准包括专注于自闭症与该通路之间联系的实验研究，并通过SYRCLE的偏倚风险工具确保质量评估。总体而言，纳入的文章强调了该通路在自闭症中发现的异常情况中的可能作用，这些异常影响了能量代谢、氧化应激和神经发生等过程。这些改变可能通过影响突触传递和线粒体功能而成为自闭症行为的基础。
