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微小RNA参与调控成体神经发生的复杂回路。

MicroRNAs Engage in Complex Circuits Regulating Adult Neurogenesis.

作者信息

Stappert Laura, Klaus Frederike, Brüstle Oliver

机构信息

Institute of Reconstructive Neurobiology, Life & Brain Center, University of Bonn Medical Center, Bonn, Germany.

出版信息

Front Neurosci. 2018 Nov 5;12:707. doi: 10.3389/fnins.2018.00707. eCollection 2018.

Abstract

The finding that the adult mammalian brain is still capable of producing neurons has ignited a new field of research aiming to identify the molecular mechanisms regulating adult neurogenesis. An improved understanding of these mechanisms could lead to the development of novel approaches to delay cognitive decline and facilitate neuroregeneration in the adult human brain. Accumulating evidence suggest microRNAs (miRNAs), which represent a class of post-transcriptional gene expression regulators, as crucial part of the gene regulatory networks governing adult neurogenesis. This review attempts to illustrate how miRNAs modulate key processes in the adult neurogenic niche by interacting with each other and with transcriptional regulators. We discuss the function of miRNAs in adult neurogenesis following the life-journey of an adult-born neuron from the adult neural stem cell (NSCs) compartment to its final target site. We first survey how miRNAs control the initial step of adult neurogenesis, that is the transition of quiescent to activated proliferative adult NSCs, and then go on to discuss the role of miRNAs to regulate neuronal differentiation, survival, and functional integration of the newborn neurons. In this context, we highlight miRNAs that converge on functionally related targets or act within cross talking gene regulatory networks. The cooperative manner of miRNA action and the broad target repertoire of each individual miRNA could make the miRNA system a promising tool to gain control on adult NSCs in the context of therapeutic approaches.

摘要

成年哺乳动物大脑仍具有产生神经元的能力这一发现,引发了一个旨在确定调节成年神经发生分子机制的新研究领域。对这些机制更深入的理解可能会带来新方法的开发,以延缓认知衰退并促进成人大脑的神经再生。越来越多的证据表明,作为一类转录后基因表达调节因子的微小RNA(miRNA),是控制成年神经发生的基因调控网络的关键部分。本综述试图阐述miRNA如何通过相互作用以及与转录调节因子相互作用来调节成年神经发生微环境中的关键过程。我们按照成年新生神经元从成年神经干细胞(NSC)区室到其最终靶位点的生命历程,讨论miRNA在成年神经发生中的功能。我们首先探讨miRNA如何控制成年神经发生的起始步骤,即静止的成年NSC向激活的增殖性成年NSC的转变,然后继续讨论miRNA在调节新生神经元的神经元分化、存活和功能整合中的作用。在此背景下,我们重点介绍了在功能相关靶点上汇聚或在相互作用的基因调控网络中起作用的miRNA。miRNA作用的协同方式以及每个miRNA广泛的靶标库,可能使miRNA系统成为在治疗方法中控制成年NSC的一个有前景的工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec07/6230569/baa2bb96851d/fnins-12-00707-g001.jpg

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