Autism spectrum disorder (ASD) is a debilitating brain illness causing social deficits, delayed development and repetitive behaviors. ASD is a heritable neurodevelopmental disorder with poorly understood and complex etiology. The central dopaminergic system is strongly implicated in ASD pathogenesis. Genes encoding various elements of this system (including dopamine receptors, the dopamine transporter or enzymes of synthesis and catabolism) have been linked to ASD. Here, we comprehensively evaluate known molecular interactors of dopaminergic genes, and identify their potential molecular partners within up/down-steam signaling pathways associated with dopamine. These in silico analyses allowed us to construct a map of molecular pathways, regulated by dopamine and involved in ASD. Clustering these pathways reveals groups of genes associated with dopamine metabolism, encoding proteins that control dopamine neurotransmission, cytoskeletal processes, synaptic release, Ca(2+) signaling, as well as the adenosine, glutamatergic and gamma-aminobutyric systems. Overall, our analyses emphasize the important role of the dopaminergic system in ASD, and implicate several cellular signaling processes in its pathogenesis.

译文

自闭症谱系障碍 (ASD) 是一种使人衰弱的脑部疾病,会导致社会缺陷,发育延迟和重复行为。ASD是一种遗传性神经发育障碍,病因尚不清楚且复杂。中枢多巴胺能系统与ASD发病机制密切相关。编码该系统各种元素的基因 (包括多巴胺受体,多巴胺转运蛋白或合成和分解代谢的酶) 已与ASD相关。在这里,我们全面评估多巴胺能基因的已知分子相互作用,并在与多巴胺相关的上/下蒸汽信号通路中确定其潜在的分子伙伴。这些计算机分析使我们能够构建由多巴胺调节并参与ASD的分子途径图。对这些途径进行聚类揭示了与多巴胺代谢相关的基因组,编码控制多巴胺神经传递,细胞骨架过程,突触释放,Ca(2) 信号传导以及腺苷,谷氨酸能和 γ-氨基丁酸系统的蛋白质。总的来说,我们的分析强调了多巴胺能系统在ASD中的重要作用,并暗示了其发病机理中的几个细胞信号过程。

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