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自闭症谱系障碍:神经发育风险因素、生物学机制与精准治疗

Autism Spectrum Disorder: Neurodevelopmental Risk Factors, Biological Mechanism, and Precision Therapy.

作者信息

Wang Ling, Wang Binquan, Wu Chunyan, Wang Jie, Sun Mingkuan

机构信息

The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.

出版信息

Int J Mol Sci. 2023 Jan 17;24(3):1819. doi: 10.3390/ijms24031819.

Abstract

Autism spectrum disorder (ASD) is a heterogeneous, behaviorally defined neurodevelopmental disorder. Over the past two decades, the prevalence of autism spectrum disorders has progressively increased, however, no clear diagnostic markers and specifically targeted medications for autism have emerged. As a result, neurobehavioral abnormalities, neurobiological alterations in ASD, and the development of novel ASD pharmacological therapy necessitate multidisciplinary collaboration. In this review, we discuss the development of multiple animal models of ASD to contribute to the disease mechanisms of ASD, as well as new studies from multiple disciplines to assess the behavioral pathology of ASD. In addition, we summarize and highlight the mechanistic advances regarding gene transcription, RNA and non-coding RNA translation, abnormal synaptic signaling pathways, epigenetic post-translational modifications, brain-gut axis, immune inflammation and neural loop abnormalities in autism to provide a theoretical basis for the next step of precision therapy. Furthermore, we review existing autism therapy tactics and limits and present challenges and opportunities for translating multidisciplinary knowledge of ASD into clinical practice.

摘要

自闭症谱系障碍(ASD)是一种异质性的、基于行为定义的神经发育障碍。在过去二十年中,自闭症谱系障碍的患病率逐渐上升,然而,尚未出现明确的诊断标志物和专门针对自闭症的药物。因此,ASD中的神经行为异常、神经生物学改变以及新型ASD药物治疗的开发需要多学科合作。在本综述中,我们讨论了多种ASD动物模型的发展,以促进对ASD疾病机制的理解,以及多学科的新研究,以评估ASD的行为病理学。此外,我们总结并强调了自闭症在基因转录、RNA和非编码RNA翻译、异常突触信号通路、表观遗传翻译后修饰、脑-肠轴、免疫炎症和神经回路异常等方面的机制进展,为下一步精准治疗提供理论依据。此外,我们回顾了现有的自闭症治疗策略和局限性,并提出了将ASD多学科知识转化为临床实践的挑战和机遇。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4b9/9915249/5f884ba40c4d/ijms-24-01819-g001.jpg

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