Department of Chemical Engineering, Bogazici University, Biosystems Engineering Laboratory, Istanbul, Turkey.
Department of Industrial Engineering, Bogazici University, Socio-Economic System Dynamics Research Group (SESDYN), Istanbul, Turkey.
Brain Behav. 2023 Dec;13(12):e3273. doi: 10.1002/brb3.3273. Epub 2023 Oct 8.
The mechanism underlying autism spectrum disorder (ASD) remains incompletely understood, but researchers have identified over a thousand genes involved in complex interactions within the brain, nervous, and immune systems, particularly during the mechanism of brain development. Various contributory environmental effects including circadian rhythm have also been studied in ASD. Thus, capturing the global picture of the ASD-clock network in combined form is critical.
We reconstructed the protein-protein interaction network of ASD and circadian rhythm to understand the connection between autism and the circadian clock. A graph theoretical study is undertaken to evaluate whether the network attributes are biologically realistic. The gene ontology enrichment analyses provide information about the most important biological processes.
This study takes a fresh look at metabolic mechanisms and the identification of potential key proteins/pathways (ribosome biogenesis, oxidative stress, insulin/IGF pathway, Wnt pathway, and mTOR pathway), as well as the effects of specific conditions (such as maternal stress or disruption of circadian rhythm) on the development of ASD due to environmental factors.
Understanding the relationship between circadian rhythm and ASD provides insight into the involvement of these essential pathways in the pathogenesis/etiology of ASD, as well as potential early intervention options and chronotherapeutic strategies for treating or preventing the neurodevelopmental disorder.
自闭症谱系障碍（ASD）的发病机制仍不完全清楚，但研究人员已经发现了 1000 多个涉及大脑、神经和免疫系统的复杂相互作用的基因，尤其是在大脑发育过程中。在 ASD 中也研究了各种环境影响因素，包括昼夜节律。因此，以综合形式捕捉 ASD 时钟网络的全局图景至关重要。
我们重建了 ASD 和昼夜节律的蛋白质-蛋白质相互作用网络，以了解自闭症与生物钟之间的联系。进行了图论研究，以评估网络属性是否具有生物学现实性。基因本体富集分析提供了有关最重要的生物学过程的信息。
这项研究从代谢机制和潜在关键蛋白/途径（核糖体生物发生、氧化应激、胰岛素/IGF 途径、Wnt 途径和 mTOR 途径）的角度出发，以及特定条件（如母体应激或昼夜节律紊乱）对自闭症发展的影响，这些都归因于环境因素。
了解昼夜节律与 ASD 之间的关系有助于深入了解这些必需途径在 ASD 发病机制/病因学中的作用，以及治疗或预防神经发育障碍的潜在早期干预选择和时间治疗策略。
