Department of Biochemistry and Molecular Medicine, Institute for Pediatric Regenerative Medicine of Shriners Hospitals for Children, University of California at Davis School of Medicine, 2425 Stockton Blvd, Sacramento, CA, 95817, USA.
J Neurodev Disord. 2019 Jun 15;11(1):10. doi: 10.1186/s11689-019-9268-y.
The development of an autistic brain is a highly complex process as evident from the involvement of various genetic and non-genetic factors in the etiology of the autism spectrum disorder (ASD). Despite being a multifactorial neurodevelopmental disorder, autistic patients display a few key characteristics, such as the impaired social interactions and elevated repetitive behaviors, suggesting the perturbation of specific neuronal circuits resulted from abnormal signaling pathways during brain development in ASD. A comprehensive review for autistic signaling mechanisms and interactions may provide a better understanding of ASD etiology and treatment.
Recent studies on genetic models and ASD patients with several different mutated genes revealed the dysregulation of several key signaling pathways, such as WNT, BMP, SHH, and retinoic acid (RA) signaling. Although no direct evidence of dysfunctional FGF or TGF-β signaling in ASD has been reported so far, a few examples of indirect evidence can be found. This review article summarizes how various genetic and non-genetic factors which have been reported contributing to ASD interact with WNT, BMP/TGF-β, SHH, FGF, and RA signaling pathways. The autism-associated gene ubiquitin-protein ligase E3A (UBE3A) has been reported to influence WNT, BMP, and RA signaling pathways, suggesting crosstalk between various signaling pathways during autistic brain development. Finally, the article comments on what further studies could be performed to gain deeper insights into the understanding of perturbed signaling pathways in the etiology of ASD.
The understanding of mechanisms behind various signaling pathways in the etiology of ASD may help to facilitate the identification of potential therapeutic targets and design of new treatment methods.
自闭症谱系障碍（ASD）的病因涉及多种遗传和非遗传因素，这表明自闭症大脑的发育是一个高度复杂的过程。尽管自闭症是一种多因素神经发育障碍，但自闭症患者表现出一些关键特征，例如社交互动受损和重复性行为增加，这表明在 ASD 大脑发育过程中，异常信号通路导致特定神经元回路的紊乱。全面综述自闭症信号机制和相互作用可能有助于更好地理解 ASD 的病因和治疗方法。
最近的遗传模型和 ASD 患者的研究表明，几种不同突变基因导致了几个关键信号通路的失调，如 WNT、BMP、SHH 和视黄酸（RA）信号通路。尽管目前尚未报道 ASD 中 FGF 或 TGF-β信号通路功能失调的直接证据，但可以找到一些间接证据的例子。这篇综述文章总结了已报道的导致 ASD 的各种遗传和非遗传因素如何与 WNT、BMP/TGF-β、SHH、FGF 和 RA 信号通路相互作用。与自闭症相关的基因泛素蛋白连接酶 E3A（UBE3A）已被报道影响 WNT、BMP 和 RA 信号通路，这表明自闭症大脑发育过程中各种信号通路之间存在串扰。最后，文章评论了可以进行哪些进一步的研究，以更深入地了解 ASD 病因中失调信号通路的情况。
了解 ASD 病因中各种信号通路的机制可能有助于促进潜在治疗靶点的识别和新治疗方法的设计。
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