Karaivazoglou Katerina, Triantos Christos, Aggeletopoulou Ioanna
Department of Psychiatry, University of Patras, 26504 Patras, Greece.
Division of Gastroenterology, Department of Internal Medicine, University of Patras, 26504 Patras, Greece.
Biomedicines. 2025 Jul 24;13(8):1808. doi: 10.3390/biomedicines13081808.
: Neurodevelopmental disorders, including autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), are increasingly recognized as conditions arising from multifaceted interactions among genetic predisposition, environmental exposures, and epigenetic modifications. Among epigenetic mechanisms, non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and PIWI-interacting RNAs (piRNAs), have gained attention as pivotal regulators of gene expression during neurodevelopment. These RNA species do not encode proteins but modulate gene expression at transcriptional and post-transcriptional levels, thereby influencing neuronal differentiation, synaptogenesis, and plasticity. : This systematic review critically examines and synthesizes the most recent findings, particularly in the post-COVID transcriptomic research era, regarding the role of ncRNAs in the pathogenesis, diagnosis, and potential treatment of neurodevelopmental disorders. : A comprehensive literature search was conducted to identify studies reporting on the expression profiles, functional implications, and clinical relevance of ncRNAs in neurodevelopmental disorders, across both human and animal models. : Here, we highlight that multiple classes of ncRNAs are differentially expressed in individuals with ASD and ADHD. Notably, specific miRNAs and lncRNAs demonstrate potential as diagnostic biomarkers with high sensitivity and specificity. Functional studies further reveal that ncRNAs actively contribute to pathogenic mechanisms by modulating neuronal gene networks. : Emerging experimental data indicate that the exogenous administration of certain ncRNAs may reverse molecular and behavioral phenotypes, supporting their therapeutic promise. These findings broaden our understanding of neurodevelopmental regulation and open new avenues for personalized diagnostics and targeted interventions in clinical neuropsychiatry.
神经发育障碍，包括自闭症谱系障碍（ASD）和注意力缺陷多动障碍（ADHD），越来越被认为是由遗传易感性、环境暴露和表观遗传修饰之间的多方面相互作用引起的疾病。在表观遗传机制中，非编码RNA（ncRNA），包括微小RNA（miRNA）、长链非编码RNA（lncRNA）和PIWI相互作用RNA（piRNA），作为神经发育过程中基因表达的关键调节因子受到关注。这些RNA种类不编码蛋白质，但在转录和转录后水平调节基因表达，从而影响神经元分化、突触形成和可塑性。
本系统综述批判性地审视并综合了最新研究结果，特别是在新冠疫情后的转录组学研究时代，关于ncRNA在神经发育障碍的发病机制、诊断和潜在治疗中的作用。
进行了全面的文献检索，以识别关于ncRNA在神经发育障碍中的表达谱、功能意义和临床相关性的研究，涵盖人类和动物模型。
在此，我们强调多类ncRNA在ASD和ADHD个体中差异表达。值得注意的是，特定的miRNA和lncRNA显示出作为具有高灵敏度和特异性的诊断生物标志物的潜力。功能研究进一步表明，ncRNA通过调节神经元基因网络积极参与致病机制。
新出现的实验数据表明，某些ncRNA的外源给药可能逆转分子和行为表型，支持它们的治疗前景。这些发现拓宽了我们对神经发育调节的理解，并为临床神经精神病学中的个性化诊断和靶向干预开辟了新途径。
