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MicroRNAs and Psychiatric Disorders: From Aetiology to Treatment.

MicroRNAs and psychiatric disorders: From aetiology to treatment.

机构信息

Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milan, Italy.

Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milan, Italy.

出版信息

Pharmacol Ther. 2016 Nov;167:13-27. doi: 10.1016/j.pharmthera.2016.07.006. Epub 2016 Jul 22.

Abstract

The emergence of psychiatric disorders relies on the interaction between genetic vulnerability and environmental adversities. Several studies have demonstrated a crucial role for epigenetics (e.g. DNA methylation, post-translational histone modifications and microRNA-mediated post-transcriptional regulation) in the translation of environmental cues into adult behavioural outcome, which can prove to be harmful thus increasing the risk to develop psychopathology. Within this frame, non-coding RNAs, especially microRNAs, came to light as pivotal regulators of many biological processes occurring in the Central Nervous System, both during the neuronal development as well as in the regulation of adult function, including learning, memory and neuronal plasticity. On these basis, in recent years it has been hypothesised a central role for microRNA modulation and expression regulation in many brain disorders, including neurodegenerative disorders and mental illnesses. Indeed, the aim of the present review is to present the most recent state of the art regarding microRNA involvement in psychiatric disorders. We will first describe the mechanisms that regulate microRNA biogenesis and we will report evidences of microRNA dysregulation in peripheral body fluids, in postmortem brain tissues from patients suffering from psychopathology as well as in animal models. Last, we will discuss the potential to consider microRNAs as putative target for pharmacological intervention, using common psychotropic drugs or more specific tools, with the aim to normalize functions that are disrupted in different psychiatric conditions.

摘要

精神障碍的出现依赖于遗传易感性和环境逆境之间的相互作用。许多研究表明,表观遗传学(例如 DNA 甲基化、翻译后组蛋白修饰和 miRNA 介导的转录后调控)在将环境线索转化为成年行为结果方面起着关键作用,这种转化可能是有害的,从而增加了发展精神病理学的风险。在这个框架内,非编码 RNA,特别是 microRNA,作为中枢神经系统中许多生物过程的关键调节剂而受到关注,这些过程既发生在神经元发育过程中,也发生在成年功能的调节过程中,包括学习、记忆和神经元可塑性。在此基础上,近年来有人假设 microRNA 调节和表达调控在许多脑疾病中,包括神经退行性疾病和精神疾病中起着核心作用。事实上,本综述的目的是介绍 microRNA 参与精神疾病的最新研究现状。我们将首先描述调节 microRNA 生物发生的机制,并报告外周体液、患有精神病理学的患者死后脑组织以及动物模型中 microRNA 失调的证据。最后,我们将讨论将 microRNAs 作为潜在的药理学干预靶点的可能性,使用常见的精神药物或更特异的工具,目的是使在不同精神疾病中失调的功能正常化。

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