Autism spectrum disorder (ASD) is characterized by neurocognitive dysfunctions, such as impaired social interaction and language learning. Gene-environment interactions have a pivotal role in ASD pathogenesis. Nuclear receptor corepressors (NCORs) are transcription co-regulators physically associated with histone deacetylases (HDACs) and many known players in ASD etiology such as transducin β-like 1 X-linked receptor 1 and methyl-CpG binding protein 2. The epigenome-modifying NCOR complex is sensitive to many ASD risk factors, including HDAC inhibitor valproic acid and a variety of endocrine factors, xenobiotic chemicals, or metabolites that can directly bind to multiple nuclear receptors. Here, we review recent studies of NCORs in neurocognition using animal models and human genetics approaches. We discuss functional interplays between NCORs and other known players in ASD etiology. It is conceivable that the NCOR complex may bridge the in utero environmental risk factors of ASD with epigenetic remodeling and can serve as a converging point for many gene-environment interactions in the pathogenesis of ASD and intellectual disability.

中文翻译：

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智力障碍和自闭症中的核受体辅助抑制因子。

自闭症谱系障碍 (ASD) 的特征是神经认知功能障碍，例如社交互动和语言学习受损。基因-环境相互作用在 ASD 发病机制中具有关键作用。核受体辅助阻遏物 (NCORs) 是与组蛋白去乙酰化酶 (HDACs) 和 ASD 病因学中许多已知参与者（如转导蛋白 β 样 1 X 连锁受体 1 和甲基-CpG 结合蛋白 2）物理相关的转录共调节子。 NCOR 复合物对许多 ASD 风险因素敏感，包括 HDAC 抑制剂丙戊酸和多种内分泌因素、异生化学物质或可直接与多个核受体结合的代谢物。在这里，我们回顾了最近使用动物模型和人类遗传学方法对神经认知中 NCORs 的研究。我们讨论了 NCOR 与 ASD 病因学中其他已知参与者之间的功能相互作用。可以想象，NCOR 复合体可以将 ASD 的子宫内环境风险因素与表观遗传重塑联系起来，并且可以作为 ASD 和智力残疾发病机制中许多基因-环境相互作用的汇合点。