Wang I-Fang, Ho Pei-Chuan, Tsai Kuen-Jer
Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.
Ph.D. Program in Medical Neuroscience, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.
Biomedicines. 2022 Aug 1;10(8):1856. doi: 10.3390/biomedicines10081856.
Learning and memory formation rely on the precise spatiotemporal regulation of gene expression, such as microRNA (miRNA)-associated silencing, to fine-tune gene expression for the induction and maintenance of synaptic plasticity. Much progress has been made in presenting direct evidence of miRNA regulation in learning and memory. Here, we summarize studies that have manipulated miRNA expression using various approaches in rodents, with changes in cognitive performance. Some of these are involved in well-known mechanisms, such as the CREB-dependent signaling pathway, and some of their roles are in fear- and stress-related disorders, particularly cognitive impairment. We also summarize extensive studies on miRNAs correlated with pathogenic tau and amyloid-β that drive the processes of Alzheimer's disease (AD). Although altered miRNA profiles in human patients with AD and in mouse models have been well studied, little is known about their clinical applications and therapeutics. Studies on miRNAs as biomarkers still show inconsistencies, and more challenges need to be confronted in standardizing blood-based biomarkers for use in AD.
学习和记忆形成依赖于基因表达的精确时空调节,如微小RNA(miRNA)相关的沉默作用,以微调基因表达,从而诱导和维持突触可塑性。在提供miRNA在学习和记忆中调节的直接证据方面已经取得了很大进展。在这里,我们总结了在啮齿动物中使用各种方法操纵miRNA表达并观察认知表现变化的研究。其中一些研究涉及众所周知的机制,如CREB依赖的信号通路,它们的一些作用与恐惧和应激相关疾病,特别是认知障碍有关。我们还总结了与驱动阿尔茨海默病(AD)进程的致病性tau蛋白和淀粉样β蛋白相关的miRNA的广泛研究。尽管对AD患者和小鼠模型中miRNA谱的改变已经进行了充分研究,但对其临床应用和治疗方法却知之甚少。作为生物标志物的miRNA研究仍然存在不一致性,在标准化用于AD的血液生物标志物方面还需要面对更多挑战。