Pritha Ariana N, Pasmay Andrea A, Noor Shahani
Department of Neurosciences and New Mexico Alcohol Research Center, School of Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
Adv Exp Med Biol. 2025;1473:129-155. doi: 10.1007/978-3-031-81908-7_7.
Despite numerous preclinical studies modeling fetal alcohol spectrum disorder (FASD)-associated neurodevelopmental deficits to date, a comprehensive molecular landscape dictating these deficits remains poorly understood. Non-coding RNAs constitute a substantial layer of epigenetic regulation of gene expression at the transcriptional, post-transcriptional, translational, and post-translational levels. Yet, little is known about the differential expression of non-coding RNAs in the context of prenatal alcohol exposure (PAE) that are mechanistically linked with FASD-related neurobehavior deficits. This chapter reviews our current knowledge from preclinical studies in non-coding RNA-mediated molecular mechanisms that may underlie FASD pathophysiology. This chapter also summarizes relevant clinical evidence and current efforts in utilizing these non-coding RNA molecules as biomarkers of PAE-associated deficits impacting central nervous system (CNS) function. Unraveling the diverse roles of various species of non-coding RNAs is critical to enhancing our comprehension of these intricate molecular pathways. Understanding these pathways would likely contribute to identifying critical molecular target(s) for developing efficient treatment strategies and prognostic and diagnostic markers fostering advancements in treating and managing FASD-related CNS dysfunction.
尽管迄今为止有大量针对胎儿酒精谱系障碍(FASD)相关神经发育缺陷的临床前研究,但决定这些缺陷的全面分子图景仍知之甚少。非编码RNA在转录、转录后、翻译和翻译后水平构成了基因表达表观遗传调控的重要层面。然而,关于产前酒精暴露(PAE)情况下与FASD相关神经行为缺陷存在机制联系的非编码RNA的差异表达,我们却知之甚少。本章回顾了临床前研究中关于非编码RNA介导的分子机制的现有知识,这些机制可能是FASD病理生理学的基础。本章还总结了相关临床证据以及目前将这些非编码RNA分子用作影响中枢神经系统(CNS)功能的PAE相关缺陷生物标志物的研究进展。阐明各种非编码RNA的不同作用对于增强我们对这些复杂分子途径的理解至关重要。了解这些途径可能有助于确定关键分子靶点,以制定有效的治疗策略以及预后和诊断标志物,推动FASD相关中枢神经系统功能障碍治疗和管理方面的进展。